Daniel Bruce Ennis

All Publications

• A gradient optimization toolbox for general purpose time-optimal MRI gradient waveform design MAGNETIC RESONANCE IN MEDICINE Loecher, M., Middione, M. J., Ennis, D. B. 2020

  View details for DOI 10.1002/mrm.28384

  View details for Web of Science ID 000545612400001

• INTRA-MYOCARDIAL ALGINATE HYDROGEL INJECTION ACTS AS A LEFT VENTRICULAR MID-WALL CONSTRAINT IN SWINE. Acta biomaterialia Sack, K. L., Aliotta, E., Choy, J. S., Ennis, D. B., Davies, N., Franz, T., Kassab, G. S., Guccione, J. M. 2020

  Abstract

  Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n=5), ischemic HF (n=5), and ischemic HF treated with alginate hydrogel injection therapy (n=5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.66 ± 0.15mum [treated] vs. 1.79 ± 0.16mum [untreated], p<0.001). Systolic contractility in treated animals improved substantially (ejection fraction = 43.9 ± 2.6% [treated] vs. 34.7 ± 2.7% [untreated], p<0.01). The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. [229 words].

  View details for DOI 10.1016/j.actbio.2020.04.033

  View details for PubMedID 32428678

• 4D Flow MR Imaging to Improve Microwave Ablation Prediction Models: A Feasibility Study in an InVivo Porcine Liver. Journal of vascular and interventional radiology : JVIR Chiang, J., Loecher, M., Moulin, K., Meloni, M. F., Raman, S. S., McWilliams, J. P., Ennis, D. B., Lee, E. W. 2020

  Abstract

  PURPOSE: To characterize the effect of hepatic vessel flow using 4-dimensional (4D) flow magnetic resonance (MR) imaging and correlate their effect on microwave ablation volumes in an invivo non-cirrhotic porcine liver model.MATERIALS AND METHODS: Microwave ablation antennas were placed under ultrasound guidance in each liver lobe of swine (n= 3 in each animal) for a total of 9 ablations. Pre- and post-ablation 4D flow MR imaging was acquired to quantify flow changes in the hepatic vasculature. Flow measurements, along with encompassed vessel size and vessel-antenna spacing, were then correlated with final ablation volume from segmented MR images.RESULTS: The linear regression model demonstrated that the preablation measurement of encompassed hepatic vein size (beta= -0.80 ±0.25, 95% confidence interval [CI] -1.15 to -0.22; P= .02) was significantly correlated to final ablation zone volume. The addition of hepatic vein flow rate found via 4D flow MRI (beta= -0.83 ± 0.65, 95% CI -2.50 to 0.84; P= .26), and distance from antenna to hepatic vein (beta= 0.26 ±0.26, 95% CI -0.40 to 0.92; P= .36) improved the model accuracy but not significantly so (multivariate adjusted R2= 0.70 vs univariate (vessel size) adjusted R2= 0.63, P= .24).CONCLUSIONS: Hepatic vein size in an encompassed ablation zone was found to be significantly correlated with final ablation zone volume. Although the univariate 4D flow MR imaging-acquired measurements alone were not found to be statistically significant, its addition to hepatic vein size improved the accuracy of the ablation volume regression model. Pre-ablation 4D flow MR imaging of the liver may assist in prospectively optimizing thermal ablation treatment.

  View details for DOI 10.1016/j.jvir.2019.11.034

  View details for PubMedID 32178944

• Evaluation of a Workflow to Define Low Specific Absorption Rate MRI Protocols for Patients With Active Implantable Medical Devices. Journal of magnetic resonance imaging : JMRI Martinez, J. A., Moulin, K., Yoo, B., Shi, Y., Kim, H. J., Villablanca, P. J., Ennis, D. B. 2020

  Abstract

  MRI exams for patients with MR-conditional active implantable medical devices (AIMDs) are contraindicated unless specific conditions are met. This limits the maximum specific absorption rate (SAR, W/kg). Currently, there is no general framework to guide meeting a lower SAR limit.To design and evaluate a workflow for modifying MRI protocols to whole-body SAR (WB-SAR ≤0.1 W/kg) and local-head SAR (LH-SAR ≤0.3 W/kg) limits while mitigating the impact on image quality and exam time.Prospective.Twenty healthy volunteers on head (n = 5), C-spine (n = 5), T-spine (n = 5), and L-spine (n = 5) with IRB consent.Vendor-provided head, C-spine, T-spine, and L-spine protocols (SARRT ) were modified to meet both low SAR targets (SARLOW ) using the proposed workflow. in vitro SNR and CNR were evaluated with a T1 -T2 phantom. in vivo image quality and clinical acceptability were scored using a 5-point Likert scale for two blinded readers.1.5T/spin-echoes, gradient-echoes.In vitro SNR and CNR values were evaluated with a repeated measures general linear model. in vivo image quality and clinical acceptability were evaluated using a generalized estimating equation analysis (GEE). The two reader's level of agreement was analyzed using Cohen's kappa statistical analysis.Using the workflow, SAR limits were met.0.12 ± 0.02 W/kg, median (SD) values for LH-SAR were 0.12 (0.02) W/kg and WB-SAR: 0.09 (0.01) W/kg. Examination time did not increase ≤2x the initial time. SARRT SNR values were higher and significantly different than SARLOW (P < 0.05). However, no significant difference was observed between the CNR values (value = 0.21). Median (IQR) CNR values were 14.2 (25.0) vs. 15.1 (9.2) for head, 12.1 (16.9) vs. 25.3 (14.2) for C-spine, 81.6 (70.1) vs. 71.0 (26.6) for T-spine, and 51.4 (52.6) vs. 37.7 (27.3) for L-spine. Image quality scores were not significantly different between SARRT and SARLOW (median [SD] scores were 4.0 [0.01] vs. 4.3 [0.2], P > 0.05).The proposed workflow provides guidance for modifying routine MRI exams to achieve low SAR limits. This can benefit patients referred for an MRI exam with low SAR MR-conditional AIMDs.1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020.

  View details for DOI 10.1002/jmri.27044

  View details for PubMedID 31922311

• Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Stoeck, C. T., Scott, A. D., Ferreira, P. F., Tunnicliffe, E. M., Teh, I., Nielles-Vallespin, S., Moulin, K., Sosnovik, D. E., Viallon, M., Croisille, P., Kozerke, S., Firmin, D. N., Ennis, D. B., Schneider, J. E. 2020; 51 (1): 319–20

  View details for DOI 10.1002/jmri.26767

  View details for Web of Science ID 000530627200031

• Optimization methods for magnetic resonance imaging gradient waveform design. NMR in biomedicine Middione, M. J., Loecher, M., Moulin, K., Ennis, D. B. 2020: e4308

  Abstract

  The development and implementation of novel MRI pulse sequences remains challenging and laborious. Gradient waveforms are typically designed using a combination of analytical and ad hoc methods to construct each gradient waveform axis independently. This strategy makes coding the pulse sequence complicated, in addition to being time inefficient. As a consequence, nearly all commercial MRI pulse sequences fail to maximize use of the available gradient hardware or efficiently mitigate physiological effects. This results in expensive MRI systems that underperform relative to their inherent hardware capabilities. To address this problem, a software solution is proposed that incorporates numerical optimization methods into MRI pulse sequence programming. Examples are shown for rotational variant vs. invariant waveform designs, acceleration nulled velocity encoding gradients, and mitigation of peripheral nerve stimulation for diffusion encoding. The application of optimization methods to MRI pulse sequence design incorporates gradient hardware limits and the prescribed MRI protocol parameters (e.g. field-of-view, resolution, gradient moments, and/or b-value) to simultaneously construct time-optimal gradient waveforms. In many cases, the resulting constrained gradient waveform design problem is convex and can be solved on-the-fly on the MRI scanner. The result is a set of multi-axis time-optimal gradient waveforms that satisfy the design constraints, thereby increasing SNR-efficiency. These optimization methods can also be used to mitigate imaging artifacts (e.g. eddy currents) or account for peripheral nerve stimulation. The result of the optimization method is to enable easier pulse sequence gradient waveform design and permit on-the-fly implementation for a range of MRI pulse sequences.

  View details for DOI 10.1002/nbm.4308

  View details for PubMedID 32342560

• Probing cardiomyocyte mobility with multi-phase cardiac diffusion tensor MRI. PloS one Moulin, K., Verzhbinsky, I. A., Maforo, N. G., Perotti, L. E., Ennis, D. B. 2020; 15 (11): e0241996

  Abstract

  Cardiomyocyte organization and performance underlie cardiac function, but the in vivo mobility of these cells during contraction and filling remains difficult to probe. Herein, a novel trigger delay (TD) scout sequence was used to acquire high in-plane resolution (1.6 mm) Spin-Echo (SE) cardiac diffusion tensor imaging (cDTI) at three distinct cardiac phases. The objective was to characterize cardiomyocyte organization and mobility throughout the cardiac cycle in healthy volunteers.Nine healthy volunteers were imaged with cDTI at three distinct cardiac phases (early systole, late systole, and diastasis). The sequence used a free-breathing Spin-Echo (SE) cDTI protocol (b-values = 350s/mm2, twelve diffusion encoding directions, eight repetitions) to acquire high-resolution images (1.6x1.6x8mm3) at 3T in ~7 minutes/cardiac phase. Helix Angle (HA), Helix Angle Range (HAR), E2 angle (E2A), Transverse Angle (TA), Mean Diffusivity (MD), diffusion tensor eigenvalues (λ1-2-3), and Fractional Anisotropy (FA) in the left ventricle (LV) were characterized.Images from the patient-specific TD scout sequence demonstrated that SE cDTI acquisition was possible at early systole, late systole, and diastasis in 78%, 100% and 67% of the cases, respectively. At the mid-ventricular level, mobility (reported as median [IQR]) was observed in HAR between early systole and late systole (76.9 [72.6, 80.5]° vs 96.6 [85.9, 100.3]°, p<0.001). E2A also changed significantly between early systole, late systole, and diastasis (27.7 [20.8, 35.1]° vs 45.2 [42.1, 49]° vs 20.7 [16.6, 26.4]°, p<0.001).We demonstrate that it is possible to probe cardiomyocyte mobility using multi-phase and high resolution cDTI. In healthy volunteers, aggregate cardiomyocytes re-orient themselves more longitudinally during contraction, while cardiomyocyte sheetlets tilt radially during wall thickening. These observations provide new insights into the three-dimensional mobility of myocardial microstructure during systolic contraction.

  View details for DOI 10.1371/journal.pone.0241996

  View details for PubMedID 33180823

• Real-time 3T MRI-guided cardiovascular catheterization in a porcine model using a glass-fiber epoxy-based guidewire. PloS one Li, X., Perotti, L. E., Martinez, J. A., Duarte-Vogel, S. M., Ennis, D. B., Wu, H. H. 2020; 15 (2): e0229711

  Abstract

  PURPOSE: Real-time magnetic resonance imaging (MRI) is a promising alternative to X-ray fluoroscopy for guiding cardiovascular catheterization procedures. Major challenges, however, include the lack of guidewires that are compatible with the MRI environment, not susceptible to radiofrequency-induced heating, and reliably visualized. Preclinical evaluation of new guidewire designs has been conducted at 1.5T. Here we further evaluate the safety (device heating), device visualization, and procedural feasibility of 3T MRI-guided cardiovascular catheterization using a novel MRI-visible glass-fiber epoxy-based guidewire in phantoms and porcine models.METHODS: To evaluate device safety, guidewire tip heating (GTH) was measured in phantom experiments with different combinations of catheters and guidewires. In vivo cardiovascular catheterization procedures were performed in both healthy (N = 5) and infarcted (N = 5) porcine models under real-time 3T MRI guidance using a glass-fiber epoxy-based guidewire. The times for each procedural step were recorded separately. Guidewire visualization was assessed by measuring the dimensions of the guidewire-induced signal void and contrast-to-noise ratio (CNR) between the guidewire tip signal void and the blood signal in real-time gradient-echo MRI (specific absorption rate [SAR] = 0.04 W/kg).RESULTS: In the phantom experiments, GTH did not exceed 0.35°C when using the real-time gradient-echo sequence (SAR = 0.04 W/kg), demonstrating the safety of the glass-fiber epoxy-based guidewire at 3T. The catheter was successfully placed in the left ventricle (LV) under real-time MRI for all five healthy subjects and three out of five infarcted subjects. Signal void dimensions and CNR values showed consistent visualization of the glass-fiber epoxy-based guidewire in real-time MRI. The average time (minutes:seconds) for the catheterization procedure in all subjects was 4:32, although the procedure time varied depending on the subject's specific anatomy (standard deviation = 4:41).CONCLUSIONS: Real-time 3T MRI-guided cardiovascular catheterization using a new MRI-visible glass-fiber epoxy-based guidewire is feasible in terms of visualization and guidewire navigation, and safe in terms of radiofrequency-induced guidewire tip heating.

  View details for DOI 10.1371/journal.pone.0229711

  View details for PubMedID 32102092

• Prostate diffusion MRI with minimal echo time using eddy current nulled convex optimized diffusion encoding. Journal of magnetic resonance imaging : JMRI Zhang, Z., Moulin, K., Aliotta, E., Shakeri, S., Afshari Mirak, S., Hosseiny, M., Raman, S., Ennis, D. B., Wu, H. H. 2019

  Abstract

  BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI.PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE.STUDY TYPE: Prospective cohort study.POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27±3years old), and five prostate cancer patients (62±7years old).FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI.ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6*1.6mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6*1.6mm2 , pF = off; 1.0* 1.0mm2 , pF = 6/8).STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P<0.05 considered significant).RESULTS: Eddy current suppression with ENCODE was comparable to bipolar encoding (mean coefficient of variation across three diffusion directions of 9.4% and 9%). For a standard-resolution protocol, ENCODE achieved similar TE as monopolar and reduced TE by 14 msec compared to bipolar, resulting in 27% and 29% higher mean SNR in prostate transition zone (TZ) and peripheral zone (PZ) (P<0.05) compared to bipolar, respectively. For higher-resolution protocols, ENCODE achieved the shortest TE (67 msec), with 17-21% and 58-70% higher mean SNR compared to monopolar (TE = 77 msec) and bipolar (TE = 102 msec) in PZ and TZ (P<0.05). No significant differences were found in mean TZ (P = 0.91) and PZ ADC (P = 0.94) between the three techniques. ENCODE achieved similar or higher image quality scores than bipolar DWI in patients, with mean intraclass correlation coefficient of 0.77 for overall quality between three independent readers.DATA CONCLUSION: ENCODE minimizes TE (improves SNR) and reduces eddy-current distortion for prostate DWI compared to monopolar and bipolar encoding.LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019.

  View details for DOI 10.1002/jmri.26960

  View details for PubMedID 31625663

• It's the little things: On the complexity of planar electrode heating in MRI NEUROIMAGE Erhardt, J. B., Lottner, T., Martinez, J., Oezen, A. C., Schuettler, M., Stieglitz, T., Ennis, D. B., Bock, M. 2019; 195: 272–84

  View details for DOI 10.1016/j.neuroimage.2019.03.061

  View details for Web of Science ID 000468743000024

• MRI of Patients with Cardiac Implantable Electronic Devices CURRENT CARDIOVASCULAR IMAGING REPORTS Martinez, J. A., Ennis, D. B. 2019; 12 (7)

  View details for DOI 10.1007/s12410-019-9502-8

  View details for Web of Science ID 000469210900002

• Model of Left Ventricular Contraction: Validation Criteria and Boundary Conditions. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Ponnaluri, A. V., Verzhbinsky, I. A., Eldredge, J. D., Garfinkel, A., Ennis, D. B., Perotti, L. E. 2019; 11504: 294–303

  Abstract

  Computational models of cardiac contraction can provide critical insight into cardiac function and dysfunction. A necessary step before employing these computational models is their validation. Here we propose a series of validation criteria based on left ventricular (LV) global (ejection fraction and twist) and local (strains in a cylindrical coordinate system, aggregate cardiomyocyte shortening, and low myocardial compressibility) MRI measures to characterize LV motion and deformation during contraction. These validation criteria are used to evaluate an LV finite element model built from subject-specific anatomy and aggregate cardiomyocyte orientations reconstructed from diffusion tensor MRI. We emphasize the key role of the simulation boundary conditions in approaching the physiologically correct motion and strains during contraction. We conclude by comparing the global and local validation criteria measures obtained using two different boundary conditions: the first constraining the LV base and the second taking into account the presence of the pericardium, which leads to greatly improved motion and deformation.

  View details for DOI 10.1007/978-3-030-21949-9_32

  View details for PubMedID 31231721

• Highly accelerated, model-free diffusion tensor MRI reconstruction using neural networks MEDICAL PHYSICS Aliotta, E., Nourzadeh, H., Sanders, J., Muller, D., Ennis, D. B. 2019; 46 (4): 1581–91

  View details for DOI 10.1002/mp.13400

  View details for Web of Science ID 000467097200008

• It's the little things: On the complexity of planar electrode heating in MRI. NeuroImage Erhardt, J. B., Lottner, T., Martinez, J., Ozen, A. C., Schuettler, M., Stieglitz, T., Ennis, D. B., Bock, M. 2019

  Abstract

  Neurological disorders are increasingly analysed and treated with implantable electrodes, and patients with such electrodes are studied with MRI despite the risk of radio-frequency (RF) induced heating during the MRI exam. Recent clinical research suggests that electrodes with smaller diameters of the electrical interface between implant and tissue are beneficial; however, the influence of this electrode contact diameter on RF-induced heating has not been investigated. In this work, electrode contact diameters between 0.3 and 4 mm of implantable electrodes appropriate for stimulation and electrocorticography were evaluated in a 1.5 T MRI system. In situ temperature measurements adapted from the ASTM standard test method were performed and complemented by simulations of the specific absorption rate (SAR) to assess local SAR values, temperature increase and the distribution of dissipated power. Measurements showed temperature changes between 0.8 K and 53 K for different electrode contact diameters, which is well above the legal limit of 1 K. Systematic errors in the temperature measurements are to be expected, as the temperature sensors may disturb the heating pattern near small electrodes. Compared to large electrodes, simulations suggest that small electrodes are subject to less dissipated power, but more localized power density. Thus, smaller electrodes might be classified as safe in current certification procedures but may be more likely to burn adjacent tissue. To assess these local heating phenomena, smaller temperature sensors or new non-invasive temperature sensing methods are needed.

  View details for PubMedID 30935911

• Time-optimized 4D phase contrast MRI with real-time convex optimization of gradient waveforms and fast excitation methods. Magnetic resonance in medicine Loecher, M., Magrath, P., Aliotta, E., Ennis, D. B. 2019

  Abstract

  PURPOSE: To shorten 4D flow acquisitions by shortening TRs with fast RF pulses and gradient waveforms. Real-time convex optimization is used to generate these gradients waveforms on the scanner.THEORY AND METHODS: RF and slab-select waveforms were shortened with a minimum phase SLR excitation and the time-optimal variable-rate selective excitation method. Real-time convex optimization was used to shorten bipolar and spoiler gradients by finding the shortest gradient waveforms that satisfied constraints on scan parameters, gradient hardware, M0 , M1 , and peripheral nerve stimulation. Waveforms were calculated and TE and/or TR values were compared for a range of scan parameters and compared to a conventional 4D flow sequence. The method was tested in flow phantoms, and in the aorta and neurovasculature of volunteers (N = 10). Additionally, eddy current error was measured in a large phantom.RESULTS: TEs and TRs were shortened by 21-32% and 20-34%, respectively, compared to the conventional sequence over a range of scan parameters. Bland-Altman analysis of 2 flow phantom configurations showed flow rate bias of 0.3 mL/s and limits of agreement (LOA) of [-6.9, 7.5] mL/s for a cardiac phantom and a bias of -0.1 mL/s with LOA = [-0.4, 0.2] mL/s for a neuro phantom. Similar agreement was also seen for flow measurements in volunteers (bias = -1.0 and -0.1 mL/s, LOA = [-34.9, 33.0] and [-0.7, 0.6] mL/s). Measured eddy currents were 39% larger with the CVX + mpVERSE method.CONCLUSION: The real-time optimized 4D flow gradients and fast slab-selection excitation methods produced up to 34% faster TRs with excellent flow measurement agreement compared to a conventional 4D flow sequence.

  View details for DOI 10.1002/mrm.27716

  View details for PubMedID 30859606

• Highly Accelerated, Model-Free Diffusion Tensor MRI Reconstruction Using Neural Networks. Medical physics Aliotta, E., Nourzadeh, H., Sanders, J., Muller, D., Ennis, D. B. 2019

  Abstract

  PURPOSE: To develop a neural network that accurately performs Diffusion Tensor MRI (DTI) reconstruction from highly accelerated scans.MATERIALS AND METHODS: This retrospective study was conducted using data acquired between 2013 and 2018 and was approved by the local institutional review board. DTI acquired in healthy volunteers (N=10) were used to train a neural network, DiffNet, to reconstruct fractional anisotropy (FA) and mean diffusivity (MD) maps from small subsets of acquired DTI data with between three and 20 diffusion encoding directions. FA and MD maps were then reconstructed in volunteers and in patients with glioblastoma multiforme (GBM, N=12) using both DiffNet and conventional reconstructions. Accuracy and precision were quantified in volunteer scans and compared between reconstructions. The accuracy of tumor delineation was compared between reconstructed patient data by evaluating agreement between DTI-derived tumor volumes and volumes defined by contrast enhanced T1-weighted MRI. Comparisons were performed using areas under the receiver operating characteristic curves (AUC).RESULTS: DiffNet FA reconstructions were more accurate and precise compared with conventional reconstructions for all acceleration factors. DiffNet permitted reconstruction with only three diffusion encoding directions with significantly lower bias than the conventional method using six directions (0.01±0.01 vs. 0.06±0.01, p<0.001). While MD-based tumor delineation was not substantially different with DiffNet (AUC range: 0.888-0.902), DiffNet FA had higher AUC than conventional reconstructions for fixed scan time and achieved similar performance with shorter scans (conventional, six directions: AUC=0.926, DiffNet, three directions: AUC=0.920).CONCLUSION: DiffNet improved DTI reconstruction accuracy, precision, and tumor delineation performance in GBM while permitting reconstruction from only three diffusion encoding directions. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30677141

• Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging. Journal of magnetic resonance imaging : JMRI Stoeck, C. T., Scott, A. D., Ferreira, P. F., Tunnicliffe, E. M., Teh, I., Nielles-Vallespin, S., Moulin, K., Sosnovik, D. E., Viallon, M., Croisille, P., Kozerke, S., Firmin, D. N., Ennis, D. B., Schneider, J. E. 2019

  View details for PubMedID 31034705

• Estimating Aggregate Cardiomyocyte Strain Using In Vivo Diffusion and Displacement Encoded MRI. IEEE transactions on medical imaging Verzhbinsky, I. A., Perotti, L. E., Moulin, K., Cork, T. E., Loecher, M., Ennis, D. B. 2019

  Abstract

  Changes in left ventricular (LV) aggregate cardiomyocyte orientation and deformation underlie cardiac function and dysfunction. As such, in vivo aggregate cardiomyocyte "myofiber" strain (Eff) has mechanistic significance, but currently there exists no established technique to measure in vivo Eff. The objective of this work is to describe and validate a pipeline to compute in vivo Eff from magnetic resonance imaging (MRI) data. Our pipeline integrates LV motion from multi-slice Displacement ENcoding with Stimulated Echoes (DENSE) MRI with in vivo LV microstructure from cardiac Diffusion Tensor Imaging (cDTI) data. The proposed pipeline is validated using an analytical deforming heart-like phantom. The phantom is used to evaluate 3D cardiac strains computed from a widely available, open-source DENSE Image Analysis Tool. Phantom evaluation showed that a DENSE MRI signal-to-noise ratio (SNR) ≥ 20 is required to compute Eff with near-zero median strain bias and within a strain tolerance of 0.06. Circumferential and longitudinal strains are also accurately measured under the same SNR requirements, however, radial strain exhibits a median epicardial bias of -0.10 even in noise-free DENSE data. The validated framework is applied to experimental DENSE MRI and cDTI data acquired in eight (N = 8) healthy swine. The experimental study demonstrated that Eff has decreased transmural variability compared to radial and circumferential strains. The spatial uniformity and mechanistic significance of in vivo Eff make it a compelling candidate for characterization and early detection of cardiac dysfunction.

  View details for DOI 10.1109/TMI.2019.2933813

  View details for PubMedID 31398112

• Patient Orientation Affects Lead-Tip Heating of Cardiac Active Implantable Medical Devices during MRI. Radiology. Cardiothoracic imaging Martinez, J. A., Serano, P., Ennis, D. B. 2019; 1 (3): e190006

  Abstract

  To evaluate changes in patient orientation to mitigate radiofrequency-induced lead-tip heating (LTH) during MRI.LTH was evaluated for device type, lead path, and distance to the isocenter of a 1.5-T MRI system. LTH for 378 conditions in both head-first (HF) and feet-first (FF) orientations was measured for nine MRI-unsafe cardiac active implantable medical devices (AIMDs) placed along three (two anatomic, one planar) left-sided lead paths at nine landmark locations. The devices were exposed to 5 minutes of continuous radiofrequency energy at 4 W/kg whole-body specific absorption rate.LTH was greater in HF than in FF orientation for the planar and one anatomic lead path (P < .05). LTH was significantly affected by lead path, distance to isocenter, and patient orientation (all P < .05), but not by cardiac AIMD device type. Maximum LTH was observed in an HF orientation for the planar lead path when the lead tip was at isocenter (right ventricular [RV] lead: 32.0 °C ± 16.3 [standard deviation], right atrial [RA] lead: 16.1°C ± 9.3). In the FF orientation, LTH was significantly reduced (RV lead: 1.6°C ± 1.4; mean RA lead: 0.5°C ± 1.0; P = .008).LTH for supine FF patient orientations among patients with anterior left-sided cardiac AIMDs can be significantly lower than LTH for supine HF orientations. There was no scenario in which LTH was significantly worse in the FF position. Changing patient orientation is a simple method to reduce radiofrequency-induced LTH.© RSNA, 2019See also the commentary by Litt in this issue.

  View details for DOI 10.1148/ryct.2019190006

  View details for PubMedID 32076667

  View details for PubMedCentralID PMC6735361

• High-Resolution Ex Vivo Microstructural MRI After Restoring Ventricular Geometry via 3D Printing. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Cork, T. E., Perotti, L. E., Verzhbinsky, I. A., Loecher, M., Ennis, D. B. 2019; 11504: 177–86

  Abstract

  Computational modeling of the heart requires accurately incorporating both gross anatomical detail and local microstructural information. Together, these provide the necessary data to build 3D meshes for simulation of cardiac mechanics and electrophysiology. Recent MRI advances make it possible to measure detailed heart motion in vivo, but in vivo microstructural imaging of the heart remains challenging. Consequently, the most detailed measurements of microstructural organization and microanatomical infarct details are obtained ex vivo. The objective of this work was to develop and evaluate a new method for restoring ex vivo ventricular geometry to match the in vivo configuration. This approach aids the integration of high-resolution ex vivo microstructural information with in vivo motion measurements. The method uses in vivo cine imaging to generate surface meshes, then creates a 3D printed left ventricular (LV) blood pool cast and a pericardial mold to restore the ex vivo cardiac geometry to a mid-diastasis reference configuration. The method was evaluated in healthy (N = 7) and infarcted (N = 3) swine. Dice similarity coefficients were calculated between in vivo and ex vivo images for the LV cavity (0.93 ± 0.01), right ventricle (RV) cavity (0.80 ± 0.05), and the myocardium (0.72 ± 0.04). The R 2 coefficient between in vivo and ex vivo LV and RV cavity volumes were 0.95 and 0.91, respectively. These results suggest that this method adequately restores ex vivo geometry to match in vivo geometry. This approach permits a more precise incorporation of high-resolution ex vivo anatomical and microstructural data into computational models that use in vivo data for simulation of cardiac mechanics and electrophysiology.

  View details for DOI 10.1007/978-3-030-21949-9_20

  View details for PubMedID 31432042

  View details for PubMedCentralID PMC6701689

• Cardiac MRI biomarkers for Duchenne muscular dystrophy. Biomarkers in medicine Magrath, P., Maforo, N., Renella, P., Nelson, S. F., Halnon, N., Ennis, D. B. 2018

  Abstract

  Duchenne muscular dystrophy (DMD) is a fatal inherited genetic disorder that results in progressive muscle weakness and ultimately loss of ambulation, respiratory failure and heart failure. Cardiac MRI (MRI) plays an increasingly important role in the diagnosis and clinical care of boys with DMD and associated cardiomyopathies. Conventional cardiac MRI biomarkers permit measurements of global cardiac function and presence of fibrosis, but changes in these measures are late manifestations. Emerging MRI biomarkers of myocardial function and structure include the estimation of rotational mechanics and regional strain using MRI tagging; T1-mapping; and T2-mapping, a marker of inflammation, edema and fat. These emerging biomarkers provide earlier insights into cardiac involvement in DMD, improving patient care and aiding the evaluation of emerging therapies.

  View details for DOI 10.2217/bmm-2018-0125

  View details for PubMedID 30499689

• Effect of flow-encoding strength on intravoxel incoherent motion in the liver. Magnetic resonance in medicine Moulin, K., Aliotta, E., Ennis, D. B. 2018

  Abstract

  PURPOSE: To study the impact of variable flow-encoding strength on intravoxel incoherent motion (IVIM) liver imaging of diffusion and perfusion.THEORY: Signal attenuation in DWI arises from (1) intravoxel microvascular blood flow, which depends on the flow-encoding strength alpha (first gradient moment) of the diffusion-encoding waveform, and (2) intravoxel spin diffusion, which depends on the b-value of the diffusion-encoding gradient waveforms alpha and b-value. Both are linked to the diffusion-encoding gradient waveform and conventionally are not independently controlled.METHODS: In this work a convex optimization framework was used to generate gradient waveforms with independent alpha and b-value. Thirty-six unique alpha and b-value sample points from 5 different gradient waveforms were used to reconstruct perfusion fraction (f), coefficient of diffusion (D), and blood velocity standard deviation (Vb ) maps using a recently proposed IVIM model. Faster acquisition strategies were evaluated with 1000 random subsampling strategies of 16, 8, and 4 alpha and b-value. Among the subsampled reconstructions, the sampling schemes that minimized the difference with the fully sampled reconstruction were reported.RESULTS: Healthy volunteers (N = 9) were imaged on a 3T scanner. Liver perfusion and diffusion estimates using the fully sampled IVIM method were f = 0.19 ± 0.06, D = 1.15 ± 0.15 * 10-3 mm2 /s, and Vb = 5.22 ± 3.86 mm/s. No statistical differences were found between the fully sampled and 2-times undersampled reconstruction (f = 0.2 ± 0.07, D = 1.19 ± 0.15 * 10-3 mm2 /s, Vb = 5.79 ± 3.43 mm/s); 4-times undersampled (f = 0.2 ± 0.06, D = 1.15 ± 0.17 * 10-3 mm2 /s, Vb = 4.66 ± 3.61 mm/s), or 8-times undersampled ( f = 0.2 ± 0.06, D = 1.23 ± 0.22 * 10-3 mm2 /s, Vb = 4.99 ± 3.82 mm/s) approaches.CONCLUSION: We demonstrate the IVIM signal's dependence on the b-value, the diffusion-encoding time and the flow-encoding strength and observe in vivo the ballistic regime signature of microperfusion in the liver. This work also demonstrates that using an IVIM model and sampling scheme matched to the ballistic regime, pixel-wise IVIM parameter maps are possible when sampling as few as 4 IVIM signals.

  View details for DOI 10.1002/mrm.27490

  View details for PubMedID 30276853

• Quantifying precision in cardiac diffusion tensor imaging with second-order motion-compensated convex optimized diffusion encoding MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Magrath, P., Ennis, D. B. 2018; 80 (3): 1074–87

  Abstract

  To quantify the precision of in vivo cardiac DTI (cDTI) acquired with a spin echo, first- and second-order motion-compensated (M1 M2 ), convex optimized diffusion encoding (CODE) sequence.Free-breathing CODE-M1 M2 cDTI were acquired in healthy volunteers (N = 10) at midsystole and diastole with 10 repeated acquisitions per phase. 95% confidence intervals of uncertainty in reconstructed diffusion tensor eigenvectors ( E→1, E→2, E→3), mean diffusivity (MD), fractional anisotropy (FA), and tensor Mode were measured using a bootstrapping approach. Trends in observed tensor metric uncertainty were evaluated as a function of scan duration, image SNR, cardiac phase, and bulk motion artifacts.For midsystolic scans including 5 signal averages (scan time: ∼5 min), the median myocardial 95% confidence intervals of uncertainties were: E→1: 15.5 ± 1.2°, E→2: 31.2 ± 3.5°, E→3: 21.8 ± 3.1°, MD: 0.38 ± 0.02 × 10-3 mm2 /s, FA: 0.20 ± 0.01, and Mode: 1.10 ± 0.08. Uncertainty in all parameters increased for diastolic scans: E→1: 31.9 ± 7.1°, E→2: 59.6 ± 6.8°, E→3 : 40.5 ± 6.4°, MD: 0.52 ± 0.09 × 10-3 mm2 /s, FA: 0.23 ± 0.01, and Mode: 1.57 ± 0.11. Diastolic cDTI also reported higher MD (MDDIA  = 1.91 ± 0.34 × 10-3 mm2 /s vs. MDSYS  = 1.58 ± 0.09 × 10-3 mm2 /s, P = 8 × 10-3 ) and lower FA values (FADIA  = 0.32 ± 0.06 vs. FASYS  = 0.37 ± 0.03, P = 0.03) .cDTI precision improved with increasing nondiffusion-weighted (b = 0) image SNR, but gains were minimal for SNR ≥ 25 (∼10 averages). cDTI precision was also sensitive to intershot bulk motion artifacts, which led to better precision for midsystolic imaging.

  View details for DOI 10.1002/mrm.27107

  View details for Web of Science ID 000435164500001

  View details for PubMedID 29427349

  View details for PubMedCentralID PMC5980763

• Microstructural Infarct Border Zone Remodeling in the Post-infarct Swine Heart Measured by Diffusion Tensor MRI FRONTIERS IN PHYSIOLOGY Kung, G. L., Vaseghi, M., Gahm, J. K., Shevtsov, J., Garfinkel, A., Shivkumar, K., Ennis, D. B. 2018; 9: 826

  Abstract

  Introduction: Computational models of the heart increasingly require detailed microstructural information to capture the impact of tissue remodeling on cardiac electromechanics in, for example, hearts with myocardial infarctions. Myocardial infarctions are surrounded by the infarct border zone (BZ), which is a site of electromechanical property transition. Magnetic resonance imaging (MRI) is an emerging method for characterizing microstructural remodeling and focal myocardial infarcts and the BZ can be identified with late gadolinium enhanced (LGE) MRI. Microstructural remodeling within the BZ, however, remains poorly characterized by MRI due, in part, to the fact that LGE and DT-MRI are not always available for the same heart. Diffusion tensor MRI (DT-MRI) can evaluate microstructural remodeling by quantifying the DT apparent diffusion coefficient (ADC, increased with decreased cellularity), fractional anisotropy (FA, decreased with increased fibrosis), and tissue mode (decreased with increased fiber disarray). The purpose of this work was to use LGE MRI in post-infarct porcine hearts (N = 7) to segment remote, BZ, and infarcted myocardium, thereby providing a basis to quantify microstructural remodeling in the BZ and infarcted regions using co-registered DT-MRI. Methods: Chronic porcine infarcts were created by balloon occlusion of the LCx. 6-8 weeks post-infarction, MRI contrast was administered, and the heart was potassium arrested, excised, and imaged with LGE MRI (0.33 × 0.33 × 0.33 mm) and co-registered DT-MRI (1 × 1 × 3 mm). Myocardium was segmented as remote, BZ, or infarct by LGE signal intensity thresholds. DT invariants were used to evaluate microstructural remodeling by quantifying ADC, FA, and tissue mode. Results: The BZ significantly remodeled compared to both infarct and remote myocardium. BZ demonstrated a significant decrease in cellularity (increased ADC), significant decrease in tissue organization (decreased FA), and a significant increase in fiber disarray (decreased tissue mode) relative to remote myocardium (all p < 0.05). Microstructural remodeling in the infarct was similar, but significantly larger in magnitude (all p < 0.05). Conclusion: DT-MRI can identify regions of significant microstructural remodeling in the BZ that are distinct from both remote and infarcted myocardium.

  View details for DOI 10.3389/fphys.2018.00826

  View details for Web of Science ID 000442432000001

  View details for PubMedID 30246802

  View details for PubMedCentralID PMC6113632

• Velocity reconstruction with nonconvex optimization for low-velocity-encoding phase-contrast MRI MAGNETIC RESONANCE IN MEDICINE Loecher, M., Ennis, D. B. 2018; 80 (1): 42–52

  Abstract

  To introduce and demonstrate a nonconvex optimization method for reconstructing velocity data from low-velocity-encoding (Venc ) phase-contrast MRI data.Solving for velocity values from phase-contrast MRI data was formulated as a nonconvex optimization problem. Weighting was added to account for intravoxel dephasing, and a Laplacian-based regularization was used to account for residual velocity aliasing. The reconstruction was tested with two low-Venc schemes: dual-Venc and a multidirectional high-moment encoding. The reconstruction method was tested in a digital simulation, in flow phantoms, and in healthy volunteers (N = 5).The nonconvex-optimization reconstruction velocity error was lower than the conventional reconstruction in simulations (4.6 versus 3.0 cm/s for multidirectional high moment, 8.3 versus 3.8 cm/s for dual-Venc ) and in flow phantoms (23.9 versus 5.9 cm/s for multidirectional high moment, 15.2 versus 6.4 cm/s for dual-Venc ). Qualitative assessment of velocity fields in all experiments, including healthy volunteers, showed decreased apparent noise in the velocity fields and fewer phase wraps. No additional velocity bias in measured velocities was seen in volunteers with the proposed method.The proposed nonconvex-optimization reconstruction method incorporates additional information to solve for velocities when using any type of low-Venc (high-moment) acquisition. The method reduces the amount of residual phase aliasing, and decreases velocity errors that result from intravoxel dephasing. These improvements allow for more robust acquisitions, and for Venc to be lowered 2 to 4 times relative to conventional acquisitions, thereby increasing the velocity-to-noise ratio. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. Magn Reson Med 80:42-52, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26997

  View details for Web of Science ID 000428703400005

  View details for PubMedID 29130519

• Construction and Validation of Subject-Specific Biventricular Finite-Element Models of Healthy and Failing Swine Hearts From High-Resolution DT-MRI FRONTIERS IN PHYSIOLOGY Sack, K. L., Aliotta, E., Ennis, D. B., Choy, J. S., Kassab, G. S., Guccione, J. M., Franz, T. 2018; 9: 539

  Abstract

  Predictive computational modeling has revolutionized classical engineering disciplines and is in the process of transforming cardiovascular research. This is particularly relevant for investigating emergent therapies for heart failure, which remains a leading cause of death globally. The creation of subject-specific biventricular computational cardiac models has been a long-term endeavor within the biomedical engineering community. Using high resolution (0.3 × 0.3 × 0.8 mm) ex vivo data, we constructed a precise fully subject-specific biventricular finite-element model of healthy and failing swine hearts. Each model includes fully subject-specific geometries, myofiber architecture and, in the case of the failing heart, fibrotic tissue distribution. Passive and active material properties are prescribed using hyperelastic strain energy functions that define a nearly incompressible, orthotropic material capable of contractile function. These materials were calibrated using a sophisticated multistep approach to match orthotropic tri-axial shear data as well as subject-specific hemodynamic ventricular targets for pressure and volume to ensure realistic cardiac function. Each mechanically beating heart is coupled with a lumped-parameter representation of the circulatory system, allowing for a closed-loop definition of cardiovascular flow. The circulatory model incorporates unidirectional fluid exchanges driven by pressure gradients of the model, which in turn are driven by the mechanically beating heart. This creates a computationally meaningful representation of the dynamic beating of the heart coupled with the circulatory system. Each model was calibrated using subject-specific experimental data and compared with independent in vivo strain data obtained from echocardiography. Our methods produced highly detailed representations of swine hearts that function mechanically in a remarkably similar manner to the in vivo subject-specific strains on a global and regional comparison. The degree of subject-specificity included in the models represents a milestone for modeling efforts that captures realism of the whole heart. This study establishes a foundation for future computational studies that can apply these validated methods to advance cardiac mechanics research.

  View details for DOI 10.3389/fphys.2018.00539

  View details for Web of Science ID 000433372700001

  View details for PubMedID 29896107

  View details for PubMedCentralID PMC5986944

• Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts MAGNETIC RESONANCE IN MEDICINE Ferreira, P. F., Nielles-Vallespin, S., Scott, A. D., de Silva, R., Kilner, P. J., Ennis, D. B., Auger, D. A., Suever, J. D., Zhong, X., Spottiswoode, B. S., Pennell, D. J., Arai, A. E., Firmin, D. N. 2018; 79 (4): 2205–15

  Abstract

  To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging.Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2 -induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data.Strain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038.The current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required. Magn Reson Med 79:2205-2215, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26850

  View details for Web of Science ID 000425026800039

  View details for PubMedID 28734017

  View details for PubMedCentralID PMC5776058

• Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion-free diffusion tensor imaging with short echo times MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Ennis, D. B. 2018; 79 (2): 663–72

  Abstract

  To design and evaluate eddy current-nulled convex optimized diffusion encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging (DTI) that is free of eddy current-induced image distortions.The EN-CODE framework was used to generate diffusion-encoding waveforms that are eddy current-compensated. The EN-CODE DTI waveform was compared with the existing eddy current-nulled twice refocused spin echo (TRSE) sequence as well as monopolar (MONO) and non-eddy current-compensated CODE in terms of echo time (TE) and image distortions. Comparisons were made in simulations, phantom experiments, and neuro imaging in 10 healthy volunteers.The EN-CODE sequence achieved eddy current compensation with a significantly shorter TE than TRSE (78 versus 96 ms) and a slightly shorter TE than MONO (78 versus 80 ms). Intravoxel signal variance was lower in phantoms with EN-CODE than with MONO (13.6 ± 11.6 versus 37.4 ± 25.8) and not different from TRSE (15.1 ± 11.6), indicating good robustness to eddy current-induced image distortions. Mean fractional anisotropy values in brain edges were also significantly lower with EN-CODE than with MONO (0.16 ± 0.01 versus 0.24 ± 0.02, P < 1 x 10-5 ) and not different from TRSE (0.16 ± 0.01 versus 0.16 ± 0.01, P = nonsignificant).The EN-CODE sequence eliminated eddy current-induced image distortions in DTI with a TE comparable to MONO and substantially shorter than TRSE. Magn Reson Med 79:663-672, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26709

  View details for Web of Science ID 000419134600006

  View details for PubMedID 28444802

• Simultaneous measurement of T-2 and apparent diffusion coefficient (T-2+ADC) in the heart with motion-compensated spin echo diffusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Moulin, K., Zhang, Z., Ennis, D. B. 2018; 79 (2): 654–62

  Abstract

  To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2 +ADC) using spin echo (SE) diffusion-weighted imaging (DWI).T2 maps from T2 +ADC were compared with single-echo SE in phantoms and with T2 -prepared (T2 -prep) balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps from T2 +ADC were compared with conventional DWI in phantoms and in vivo. T2 +ADC was also demonstrated in a patient with acute myocardial infarction (MI).Phantom T2 values from T2 +ADC were closer to a single-echo SE reference than T2 -prep bSSFP (-2.3 ± 6.0% vs 22.2 ± 16.3%; P < 0.01), and ADC values were in excellent agreement with DWI (0.28 ± 0.4%). In volunteers, myocardial T2 values from T2 +ADC were significantly shorter than T2 -prep bSSFP (35.8 ± 3.1 vs 46.8 ± 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.) different between T2 +ADC and conventional motion-compensated DWI (1.39 ± 0.18 vs 1.38 ± 0.18 mm2 /ms; P = N.S.). In the patient, T2 and ADC were both significantly elevated in the infarct compared with remote myocardium (T2 : 40.4 ± 7.6 vs 56.8 ± 22.0; P < 0.01; ADC: 1.47 ± 0.59 vs 1.65 ± 0.65 mm2 /ms; P < 0.01).T2 +ADC generated coregistered, free-breathing T2 and ADC maps in healthy volunteers and a patient with acute MI with no cost in accuracy, precision, or scan time compared with DWI. Magn Reson Med 79:654-662, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26705

  View details for Web of Science ID 000419134600005

  View details for PubMedID 28516485

  View details for PubMedCentralID PMC5891215

• TIME RESOLVED DISPLACEMENT-BASED REGISTRATION OF IN VIVO CDTI CARDIOMYOCYTE ORIENTATIONS Verzhbinsky, I. A., Magrath, P., Aliotta, E., Ennis, D. B., Perotti, L. E., IEEE IEEE. 2018: 474–78

  Abstract

  In vivo cardiac microstructure acquired using cardiac diffusion tensor imaging (cDTI) is a critical component of patient-specific models of cardiac electrophysiology and mechanics. In order to limit bulk motion artifacts and acquisition time, cDTI microstructural data is acquired at a single cardiac phase necessitating registration to the reference configuration on which the patient-specific computational models are based. Herein, we propose a method to register subject-specific microstructural data to an arbitrary cardiac phase using measured cardiac displacements. We validate our approach using a subject-specific computational phantom based on data from human subjects. Compared to a geometry-based non-rigid registration method, the displacement-based registration leads to improved accuracy (less than 1° versus 10° average median error in cardiomyocyte angular differences) and tighter confidence interval (3° versus 65° average upper limit of the 95% confidence interval).

  View details for Web of Science ID 000455045600108

  View details for PubMedID 30559922

  View details for PubMedCentralID PMC6294325

• Time resolved displacement-based registration of in vivo cDTI cardiomyocyte orientations Verzhbinsky, I. A., Magrath , P., Aliotta, E., Moulin, K., Ennis, D. B., Perotti , L. E. 2018

  View details for DOI 10.1109/ISBI.2018.8363619

• Method for the unique identification of hyperelastic material properties using full-field measures. Application to the passive myocardium material response INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Perotti, L. E., Ponnaluri, A. S., Krishnamoorthi, S., Balzani, D., Ennis, D. B., Klug, W. S. 2017; 33 (11)

  Abstract

  Quantitative measurement of the material properties (eg, stiffness) of biological tissues is poised to become a powerful diagnostic tool. There are currently several methods in the literature to estimating material stiffness, and we extend this work by formulating a framework that leads to uniquely identified material properties. We design an approach to work with full-field displacement data-ie, we assume the displacement field due to the applied forces is known both on the boundaries and also within the interior of the body of interest-and seek stiffness parameters that lead to balanced internal and external forces in a model. For in vivo applications, the displacement data can be acquired clinically using magnetic resonance imaging while the forces may be computed from pressure measurements, eg, through catheterization. We outline a set of conditions under which the least-square force error objective function is convex, yielding uniquely identified material properties. An important component of our framework is a new numerical strategy to formulate polyconvex material energy laws that are linear in the material properties and provide one optimal description of the available experimental data. An outcome of our approach is the analysis of the reliability of the identified material properties, even for material laws that do not admit unique property identification. Lastly, we evaluate our approach using passive myocardium experimental data at the material point and show its application to identifying myocardial stiffness with an in silico experiment modeling the passive filling of the left ventricle.

  View details for DOI 10.1002/cnm.2866

  View details for Web of Science ID 000415353100004

  View details for PubMedID 28098434

  View details for PubMedCentralID PMC5515704

• Terahertz Imaging of Cutaneous Edema: Correlation With Magnetic Resonance Imaging in Burn Wounds IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Bajwa, N., Sung, S., Ennis, D. B., Fishbein, M. C., Nowroozi, B. N., Ruan, D., Maccabi, A., Alger, J., St John, M. A., Grundfest, W. S., Taylor, Z. D. 2017; 64 (11): 2682–94

  Abstract

  In vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema.A partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T2-weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds.For both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 μm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis.This paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging.The ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.

  View details for DOI 10.1109/TBME.2017.2658439

  View details for Web of Science ID 000413315000018

  View details for PubMedID 28141514

• Phase-contrast MRI with hybrid one and two-sided flow-encoding and velocity spectrum separation MAGNETIC RESONANCE IN MEDICINE Wang, D., Shao, J., Ennis, D. B., Hu, P. 2017; 78 (1): 182–92

  Abstract

  To develop and evaluate a phase-contrast MRI (PC-MRI) technique with hybrid one and two-sided flow-encoding and velocity spectrum separation (HOTSPA) for accelerated blood flow and velocity measurement.In the HOTSPA technique, the two-sided flow encoding (FE) is used for two FE directions and one-sided is used for the remaining FE direction. Such a temporal modulation of the FE strategy allows for separations of the Fourier velocity spectrum into components for the flow-compensated and the three-directional velocity waveforms, accelerating PC-MRI by encoding three-directional velocities using only two repetition times (TRs) instead of four TRs as in standard PC-MRI. The HOTSPA was evaluated and compared with standard PC-MRI in the common carotid arteries of six healthy volunteers.Total volumetric flow and peak velocity measurements based on HOTSPA and the conventional PC-MRI were in good agreement with a bias of -0.005 mL (-0.1% relative bias error) for total volumetric flow and 1.21 cm/s (1.1% relative bias error) for peak velocity, although the total acquisition time was 50% of the conventional PC-MRI.The proposed HOTSPA technique achieved nearly two-fold acceleration of PC-MRI while maintaining accuracy for total volumetric flow and peak velocity quantification by separating the paired acquisitions in the Fourier velocity spectrum domain. Magn Reson Med 78:182-192, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26366

  View details for Web of Science ID 000403803900018

  View details for PubMedID 27504987

  View details for PubMedCentralID PMC5298945

• Microstructurally Anchored Cardiac Kinematics by Combining In Vivo DENSE MRI and cDTI. Functional imaging and modeling of the heart : ... International Workshop, FIMH ..., proceedings. FIMH Perotti, L. E., Magrath, P., Verzhbinsky, I. A., Aliotta, E., Moulin, K., Ennis, D. B. 2017; 10263: 381–91

  Abstract

  Metrics of regional myocardial function can detect the onset of cardiovascular disease, evaluate the response to therapy, and provide mechanistic insight into cardiac dysfunction. Knowledge of local myocardial microstructure is necessary to distinguish between isotropic and anisotropic contributions of local deformation and to quantify myofiber kinematics, a microstructurally anchored measure of cardiac function. Using a computational model we combine in vivo cardiac displacement and diffusion tensor data to evaluate pointwise the deformation gradient tensor and isotropic and anisotropic deformation invariants. In discussing the imaging methods and the model construction, we identify potential improvements to increase measurement accuracy. We conclude by demonstrating the applicability of our method to compute myofiber strain in five healthy volunteers.

  View details for DOI 10.1007/978-3-319-59448-4_36

  View details for PubMedID 29450409

• Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Ajijola, O. A., Lux, R. L., Khahera, A., Kwon, O., Aliotta, E., Ennis, D. B., Fishbein, M. C., Ardell, J. L., Shivkumar, K. 2017; 312 (3): H608–H621

  Abstract

  The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.

  View details for DOI 10.1152/ajpheart.00575.2016

  View details for Web of Science ID 000397808500026

  View details for PubMedID 28087519

  View details for PubMedCentralID PMC5402014

• Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Nielles-Vallespin, S., Khalique, Z., Ferreira, P. F., de Silva, R., Scott, A. D., Kilner, P., McGill, L., Giannakidis, A., Gatehouse, P. D., Ennis, D., Aliotta, E., Al-Khalil, M., Kellman, P., Mazilu, D., Balaban, R. S., Firmin, D. N., Arai, A. E., Pennell, D. J. 2017; 69 (6): 661–76

  Abstract

  Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function.This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM.In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients.In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001).Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

  View details for DOI 10.1016/j.jacc.2016.11.051

  View details for Web of Science ID 000396338900009

  View details for PubMedID 28183509

• Convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted MRI MAGNETIC RESONANCE IN MEDICINE Aliotta, E., Wu, H. H., Ennis, D. B. 2017; 77 (2): 717–29

  Abstract

  To evaluate convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted imaging (DWI).Diffusion-encoding gradient waveforms were designed for a range of b-values and spatial resolutions with and without motion compensation using the CODE framework. CODE, first moment (M1 ) nulled CODE-M1 , and first and second moment (M2 ) nulled CODE-M1 M2 were used to acquire neuro, liver, and cardiac ADC maps in healthy subjects (n=10) that were compared respectively to monopolar (MONO), BIPOLAR (M1  = 0), and motion-compensated (MOCO, M1  + M2  = 0) diffusion encoding.CODE significantly improved the SNR of neuro ADC maps compared with MONO (19.5 ± 2.5 versus 14.5 ± 1.9). CODE-M1 liver ADCs were significantly lower (1.3 ± 0.1 versus 1.8 ± 0.3 × 10-3 mm2 /s, ie, less motion corrupted) and more spatially uniform (6% versus 55% ROI difference) than MONO and had higher SNR than BIPOLAR (SNR = 14.9 ± 5.3 versus 8.0 ± 3.1). CODE-M1 M2 cardiac ADCs were significantly lower than MONO (1.9 ± 0.6 versus 3.8 ± 0.3 x10-3 mm2 /s) throughout the cardiac cycle and had higher SNR than MOCO at systole (9.1 ± 3.9 versus 7.0 ± 2.6) while reporting similar ADCs (1.5 ± 0.2 versus 1.4 ± 0.6 × 10-3 mm2 /s).CODE significantly improved SNR for ADC mapping in the brain, liver and heart, and significantly improved DWI bulk motion robustness in the liver and heart. Magn Reson Med 77:717-729, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26166

  View details for Web of Science ID 000394544700028

  View details for PubMedID 26900872

• Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy MAGNETIC RESONANCE IN MEDICINE Reyhan, M. L., Wang, Z., Kim, H. J., Halnon, N. J., Finn, J., Ennis, D. B. 2017; 77 (2): 864–69

  Abstract

  Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL).LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method.Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH.Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26137

  View details for Web of Science ID 000394544700045

  View details for PubMedID 26888012

  View details for PubMedCentralID PMC5927592

• Scar voltage threshold determination using ex vivo magnetic resonance imaging integration in a porcine infarct model: Influence of interelectrode distances and three-dimensional spatial effects of scar HEART RHYTHM Tung, R., Kim, S., Yagishita, D., Vaseghi, M., Ennis, D. B., Ouadah, S., Ajijola, O. A., Bradfield, J. S., Mahapatra, S., Finn, P., Shivkumar, K. 2016; 13 (10): 1993–2002

  Abstract

  Studies analyzing optimal voltage thresholds for scar detection with electroanatomic mapping frequently lack a gold standard for comparison.The purpose of this study was to use a porcine infarct model with ex vivo magnetic resonance imaging (MRI) integration to characterize the relationship between interelectrode spacing and bipolar voltage thresholds and examine the influence of 3-dimensional scar on unipolar voltages.Thirty-two combined endocardial-epicardial electroanatomic maps were created in 8 postinfarct porcine subjects (bipolar 2-mm, 5-mm, and 8-mm interelectrode spacing and unipolar) for comparison with ex vivo MRI. Two thresholds were compared: (1) 95% normal distribution and (2) best fit to MRI. Direct electrogram analysis was performed in regions across from MRI-defined scar and adjacent to scar border zone.A linear increase in optimal thresholds was observed with wider bipole spacing. The 95% thresholds for scar were lower than MRI-matched thresholds with moderate sensitivity for nontransmural scar (54% endo, 63% epi). Unipolar endocardial scar area exceeded MRI-defined scar, resulting in mismatched false scar in 5 of 8 (63%). Endocardial and epicardial unipolar voltages were lower than normal in regions adjacent and across from scar.Variations in interelectrode spacing necessitate tailored bipolar voltage thresholds to optimize scar detection. Statistical 95% thresholds appear to be conservative and not fully sensitive for the detection of scar defined by high-resolution ex vivo MRI. In the presence of endocardial scar, unipolar mapping to quantitatively characterize epicardial scar may be overly sensitive due to 3-dimensional spatial averaging.

  View details for DOI 10.1016/j.hrthm.2016.07.003

  View details for Web of Science ID 000388273900012

  View details for PubMedID 27392944

• Electrophysiology of Heart Failure Using a Rabbit Model: From the Failing Myocyte to Ventricular Fibrillation PLOS COMPUTATIONAL BIOLOGY Ponnaluri, A. S., Perotti, L. E., Liu, M., Qu, Z., Weiss, J. N., Ennis, D. B., Klug, W. S., Garfinkel, A. 2016; 12 (6): e1004968

  Abstract

  Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we compared the electrical wave propagation in one dimensional cables of healthy and failing cells. The validated cell model was then used to simulate the EP of heart failure in an anatomically accurate biventricular rabbit model. As pacing cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing. Moreover, T-wave alternans is significantly more pronounced in the failing heart. At rapid pacing, APD maps show areas of conduction block in the failing heart. Finally, accelerated pacing initiated wave reentry and breakup in the failing heart. Further, the onset of VF was not observed with an upregulation of SERCA, a potential drug therapy, using the same protocol. The changes introduced at the cell and tissue level have increased the failing heart's susceptibility to dynamic instabilities and arrhythmias under rapid pacing. However, the observed increase in arrhythmogenic potential is not due to a steepening of the restitution curve (not present in our model), but rather to a novel blocking mechanism.

  View details for DOI 10.1371/journal.pcbi.1004968

  View details for Web of Science ID 000379349700042

  View details for PubMedID 27336310

  View details for PubMedCentralID PMC4919062

• Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks PLOS COMPUTATIONAL BIOLOGY Newberry, M. G., Ennis, D. B., Savage, V. M. 2015; 11 (8): e1004455

  Abstract

  Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods-two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths.

  View details for DOI 10.1371/journal.pcbi.1004455

  View details for Web of Science ID 000360824500047

  View details for PubMedID 26317654

  View details for PubMedCentralID PMC4552567

• Left ventricular twist and shear in patients with primary mitral regurgitation JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Wang, Z., Li, M., Kim, H. J., Gupta, H., Lloyd, S. G., Dell'Italia, L. J., Denney, T., Ennis, D. B. 2015; 42 (2): 400–406

  Abstract

  To evaluate the relationship between left ventricular (LV) twist, shear, and twist-per-volume and the severity of mitral regurgitation (MR). Primary MR is a valvular disorder that induces LV dysfunction. There exist several measures of LV rotational mechanics, but it remains unclear which measure of LV dysfunction best accords with the severity of MR. We hypothesized that LV systolic twist-per-volume slope would decrease with increasing severity of MR because of both decreases in rotational mechanics and increases in stroke volumes.Normal subjects (n = 54), moderate MR patients (n = 29), and severe MR patients (n = 54) were studied. Magnetic resonance imaging (MRI) was performed on a 1.5T scanner and grid-tagged LV images were collected at the LV base and LV apex. Measures of LV rotational mechanics were derived from tagged images using Fourier Analysis of STimulated echoes (FAST).Peak systolic twist-per-volume slope was significantly different for all pairwise comparisons (P < 0.0001) and compared to normal subjects (-0.14 ± 0.05°/mL) was decreased in moderate MR (-0.12 ± 0.04°/mL) and further decreased in severe MR (-0.07 ± 0.03°/mL).Peak systolic twist-per-volume slope significantly decreased with increasing severity of MR and is therefore a suitable quantitative imaging biomarker for LV dysfunction in patients with MR.

  View details for DOI 10.1002/jmri.24811

  View details for Web of Science ID 000358258600018

  View details for PubMedID 25408263

• Phase Contrast MRI with Flow Compensation View Sharing MAGNETIC RESONANCE IN MEDICINE Wang, D., Shao, J., Rapacchi, S., Middione, M. J., Ennis, D. B., Hu, P. 2015; 73 (2): 505-513

  Abstract

  To develop and evaluate a technique for accelerating phase contrast MRI (PC-MRI) acquisitions without significant compromise in flow quantification accuracy.PC-MRI is commonly acquired using interleaved flow-compensated (FC) and flow-encoded (FE) echoes. We hypothesized that FC data, which represent background phase, do not change significantly over time. Therefore, we proposed to undersample the FC data and use an FC view sharing (FCVS) approach to synthesize a composite FC frame for each corresponding FE frame. FCVS was evaluated in a flow phantom and healthy volunteers and compared with a standard FC/FE PC-MRI.The FCVS sequence resulted in an error of 0.0% for forward flow and 2.0% for reverse flow volume when compared with FC/FE PC-MRI in a flow phantom. Measurements in the common carotid arteries showed that the FCVS method had -1.16 cm/s bias for maximum peak velocity and -0.019 mL bias in total flow, when compared with FC/FE with the same temporal resolution, but double the total acquisition time. These results represent ≤1.3% bias error in velocity and volumetric flow quantification.FCVS can accelerate PC-MRI acquisitions while maintaining flow and velocity measurement accuracy when there is limited temporal variation in the FC data.

  View details for DOI 10.1002/mrm.25133

  View details for Web of Science ID 000348139500008

  View details for PubMedID 24532480

  View details for PubMedCentralID PMC4459783

• Free-breathing variable flip angle balanced SSFP cardiac cine imaging with reduced SAR at 3T. Magnetic resonance in medicine Srinivasan, S., Kroeker, R. M., Gabriel, S., Plotnik, A., Godinez, S. R., Hu, P., Halnon, N., Finn, J. P., Ennis, D. B. 2015

  Abstract

  To develop a free-breathing variable flip angle (VFA) balanced steady-state free precession (bSSFP) cardiac cine imaging technique with reduced specific absorption rate (SAR) at 3 Tesla.Free-breathing VFA (FB-VFA) images in the short-axis and four-chamber views were acquired using an optimal VFA scheme, then compared with conventional breath-hold constant flip angle (BH-CFA) acquisitions. Two cardiac MRI experts used a 5-point scale to score images from healthy subjects (N = 10). The left ventricular ejection fraction, end diastolic volume (LVEDV), end systolic volume, stroke volume (LVSV), and end diastolic myocardial mass (LVEDM) were determined by manual contour analysis for BH-CFA and FB-VFA. A pilot evaluation of FB-VFA was performed in one patient with Duchenne muscular dystrophy.FB-VFA SAR was 25% lower than BH-CFA with similar blood-myocardium contrast. The qualitative FB-VFA score was lower than the BH-CFA for the short-axis (3.1 ± 0.5 versus 4.3 ± 0.8; P < 0.05) and the four-chamber view (3.4 ± 0.4 versus 4.6 ± 0.6; P < 0.05). The LVEDV and the LVSV were 5% and 12% larger (P < 0.05) for FB-VFA compared with BH-CFA. There was no difference in LVEDM.FB-VFA bSSFP cardiac cine imaging decreased the SAR at 3T with image quality sufficient to perform cardiac functional analysis. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26011

  View details for PubMedID 26509846

• CARDIAC MRI DERIVED EPICARDIAL FAT MAPS TO ASSIST VT ABLATION PROCEDURES FOR SUBJECTS WITH IMPLANTABLE DEVICES Zimmermann, J., Rashid, S., Hu, P., Katouzian, A., Navab, N., Ennis, D. B., IEEE IEEE. 2015: 747–50

  View details for Web of Science ID 000380546000179

• Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology PLOS ONE Krishnamoorthi, S., Perotti, L. E., Borgstrom, N. P., Ajijola, O. A., Frid, A., Ponnaluri, A. V., Weiss, J. N., Qu, Z., Klug, W. S., Ennis, D. B., Garfinkel, A. 2014; 9 (12): e114494

  Abstract

  We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

  View details for DOI 10.1371/journal.pone.0114494

  View details for Web of Science ID 000346611400048

  View details for PubMedID 25493967

  View details for PubMedCentralID PMC4262432

• Convex Gradient Optimization for Increased Spatiotemporal Resolution and Improved Accuracy in Phase Contrast MRI MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Wu, H. H., Ennis, D. B. 2014; 72 (6): 1552-1564

  Abstract

  To evaluate convex gradient optimization (CVX) for increased spatiotemporal resolution and improved accuracy for phase-contrast MRI (PC-MRI).A conventional flow-compensated and flow-encoded (FCFE) PC-MRI sequence was compared with a CVX PC-MRI sequence using numerical simulations, flow phantom experiments, and in vivo experiments. Flow measurements within the ascending aorta, main pulmonary artery, and right/left pulmonary arteries of normal volunteers (N = 10) were acquired at 3T and analyzed using a conventional FCFE sequence and a CVX sequence with either higher spatial resolution or higher temporal resolution. All sequences mitigated chemical shift-induced phase errors and used equivalent breath-hold durations.Chemical shift-optimized PC-MRI has increased sequence efficiency when using CVX, which can provide either higher spatial or higher temporal resolution compared with conventional FCFE PC-MRI. Numerical simulations, flow phantom experiments, and in vivo experiments indicate that CVX measurements of total flow and peak velocity are increased and more accurate when compared with FCFE.CVX PC-MRI increases sequence efficiency while reducing chemical shift-induced phase errors. This can be used to provide either higher spatial or higher temporal resolution than conventional chemical shift-mitigated PC-MRI methods to provide more accurate measurements of blood flow and peak velocity.

  View details for DOI 10.1002/mrm.25059

  View details for Web of Science ID 000344798300008

  View details for PubMedID 24347040

• Velocity Encoding with the Slice Select Refocusing Gradient for Faster Imaging and Reduced Chemical Shift-Induced Phase Errors MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Thompson, R. B., Ennis, D. B. 2014; 71 (6): 2014-2023

  Abstract

  To investigate a novel phase-contrast MRI velocity-encoding technique for faster imaging and reduced chemical shift-induced phase errors.Velocity encoding with the slice select refocusing gradient achieves the target gradient moment by time shifting the refocusing gradient, which enables the use of the minimum in-phase echo time (TE) for faster imaging and reduced chemical shift-induced phase errors. Net forward flow was compared in 10 healthy subjects (N = 10) within the ascending aorta (aAo), main pulmonary artery (PA), and right/left pulmonary arteries (RPA/LPA) using conventional flow compensated and flow encoded (401 Hz/px and TE = 3.08 ms) and slice select refocused gradient velocity encoding (814 Hz/px and TE = 2.46 ms) at 3 T.Improved net forward flow agreement was measured across all vessels for slice select refocused gradient compared to flow compensated and flow encoded: aAo vs. PA (1.7% ± 1.9% vs. 5.8% ± 2.8%, P = 0.002), aAo vs. RPA + LPA (2.1% ± 1.7% vs. 6.0% ± 4.3%, P = 0.03), and PA vs. RPA + LPA (2.9% ± 2.1% vs. 6.1% ± 6.3%, P = 0.04), while increasing temporal resolution (35%) and signal-to-noise ratio (33%).Slice select refocused gradient phase-contrast MRI with a high receiver bandwidth and minimum in-phase TE provides more accurate and less variable flow measurements through the reduction of chemical shift-induced phase errors and a reduced TE/repetition time, which can be used to increase the temporal/spatial resolution and/or reduce breath hold durations.

  View details for DOI 10.1002/mrm.24861

  View details for Web of Science ID 000336260900009

  View details for PubMedID 23836543

• Modeling and incorporating cardiac-induced lung tissue motion in a breathing motion model MEDICAL PHYSICS White, B. M., Santhanam, A., Thomas, D., Min, Y., Lamb, J. M., Neylon, J., Jani, S., Gaudio, S., Srinivasan, S., Ennis, D., Low, D. A. 2014; 41 (4)

  Abstract

  The purpose of this work is to develop a cardiac-induced lung motion model to be integrated into an existing breathing motion model.The authors' proposed cardiac-induced lung motion model represents the lung tissue's specific response to the subject's cardiac cycle. The model is mathematically defined as a product of a converging polynomial function h of the cardiac phase (c) and the maximum displacement y(X0) of each voxel (X0) among all the cardiac phases. The function h(c) was estimated from cardiac-gated MR imaging of ten healthy volunteers using an Akaike Information Criteria optimization algorithm. For each volunteer, a total of 24 short-axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12-15 s breath-hold maneuvers. Each view contained 30 temporal frames of equal time-duration beginning with the end-diastolic cardiac phase. The frames in each of the planar views were resampled to create a set of three-dimensional (3D) anatomical volumes representing thoracic anatomy at different cardiac phases. A 3D multiresolution optical flow deformable image registration algorithm was used to quantify the difference in tissue position between the end-diastolic cardiac phase and the remaining cardiac phases. To account for image noise, voxel displacements whose maximum values were less than 0.3 mm, were excluded. In addition, the blood vessels were segmented and excluded in order to eliminate registration artifacts caused by blood-flow.The average cardiac-induced lung motions for displacements greater than 0.3 mm were found to be 0.86 ± 0.74 and 0.97 ± 0.93 mm in the left and right lungs, respectively. The average model residual error for the ten healthy volunteers was found to be 0.29 ± 0.08 mm in the left lung and 0.38 ± 0.14 mm in the right lung for tissue displacements greater than 0.3 mm. The relative error decreased with increasing cardiac-induced lung tissue motion. While the relative error was > 60% for submillimeter cardiac-induced lung tissue motion, the relative error decreased to < 5% for cardiac-induced lung tissue motion that exceeded 10 mm in displacement.The authors' studies implied that modeling and including cardiac-induced lung motion would improve breathing motion model accuracy for tissues with cardiac-induced motion greater than 0.3 mm.

  View details for DOI 10.1118/1.4866888

  View details for Web of Science ID 000334287000041

  View details for PubMedID 24694158

  View details for PubMedCentralID PMC3987767

• Accelerating Dynamic Magnetic Resonance Imaging (MRI) for Lung Tumor Tracking Based on Low-Rank Decomposition in the Spatial-Temporal Domain: A Feasibility Study Based on Simulation and Preliminary Prospective Undersampled MRI INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sarma, M., Hu, P., Rapacchi, S., Ennis, D., Thomas, A., Lee, P., Kupelian, P., Sheng, K. 2014; 88 (3): 723–31

  Abstract

  To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking.Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis of autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data.In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details.Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.

  View details for DOI 10.1016/j.ijrobp.2013.11.217

  View details for Web of Science ID 000331726300030

  View details for PubMedID 24412430

  View details for PubMedCentralID PMC3941205

• Intra- and Interscan Reproducibility Using Fourier Analysis of STimulated Echoes (FAST) for the Rapid and Robust Quantification of Left Ventricular Twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Kim, H. J., Brown, M. S., Ennis, D. B. 2014; 39 (2): 463–68

  Abstract

  To assess the intra- and interscan reproducibility of LV twist using FAST. Assessing the reproducibility of the measurement of new MRI biomarkers is an important part of validation. Fourier Analysis of STimulated Echoes (FAST) is a new MRI tissue tagging method that has recently been shown to compare favorably with conventional estimates of left ventricular (LV) twist from cardiac tagged images, but with significantly reduced user interaction time.Healthy volunteers (N = 10) were scanned twice using FAST over 1 week. On day 1, two measurements of LV twist were collected for intrascan comparisons. Measurements for LV twist were again collected on day 8 for interscan assessment. LV short-axis tagged images were acquired on a 3 Tesla (T) scanner to ensure detectability of tags during early and mid-diastole. Peak LV twist is reported as mean ± SD. Reproducibility was assessed using the concordance correlation coefficient (CCC) and the repeatability coefficient (RC) (95% confidence interval [CI] range).Mean peak twist measurements were 13.4 ± 4.3° (day 1, scan 1), 13.6 ± 3.7° (day 1, scan 2), and 13.0 ± 2.7° (day 8). Bland-Altman analysis resulted in intra- and interscan bias and 95% CI of -0.6° [-1.0°, 1.6°] and 1.4° (-1.0°, 3.0°), respectively. The Bland-Altman RC for peak LV twist was 2.6° and 4.0° for intra- and interscan, respectively. The CCC was 0.9 and 0.6 for peak LV twist for intra- and interscan, respectively.FAST is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist that demonstrates high intrascan and moderate interscan reproducibility in preliminary studies.

  View details for DOI 10.1002/jmri.24162

  View details for Web of Science ID 000329753400027

  View details for PubMedID 23633244

  View details for PubMedCentralID PMC3751999

• Device artifact reduction for magnetic resonance imaging of patients with implantable cardioverter-defibrillators and ventricular tachycardia: Late gadolinium enhancement correlation with electroanatomic mapping HEART RHYTHM Stevens, S. M., Tung, R., Rashid, S., Gima, J., Cote, S., Pavez, G., Khan, S., Ennis, D. B., Finn, J., Boyle, N., Shivkumar, K., Hu, P. 2014; 11 (2): 289–98

  Abstract

  Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) of ventricular scar has been shown to be accurate for detection and characterization of arrhythmia substrates. However, the majority of patients referred for ventricular tachycardia (VT) ablation have an implantable cardioverter-defibrillator (ICD), which obscures image integrity and the clinical utility of MRI.The purpose of this study was to develop and validate a wideband LGE MRI technique for device artifact removal.A novel wideband LGE MRI technique was developed to allow for improved scar evaluation on patients with ICDs. The wideband technique and the standard LGE MRI were tested on 18 patients with ICDs. VT ablation was performed in 13 of 18 patients with either endocardial and/or epicardial approach and the correlation between the scar identified on MRI and electroanatomic mapping (EAM) was analyzed.Hyperintensity artifact was present in 16 of 18 of patients using standard MRI, which was eliminated using the wideband LGE and allowed for MRI interpretation in 15 of 16 patients. All patients had ICD lead characteristics confirmed as unchanged post-MRI and had no adverse events. LGE scar was seen in 11 of 18 patients. Among the 15 patients in whom wideband LGE allowed visualization of myocardium, 10 had LGE scar and 5 had normal myocardium in the regions with image artifacts when using the standard LGE. The left ventricular scar size measurements using wideband MRI and EAM were correlated with R(2) = 0.83 and P = .00003.Wideband LGE MRI improves the ability to visualize myocardium for clinical interpretation, which correlated well with EAM findings during VT ablation.

  View details for DOI 10.1016/j.hrthm.2013.10.032

  View details for Web of Science ID 000330189700019

  View details for PubMedID 24140812

  View details for PubMedCentralID PMC3946910

• Off-Resonance Insensitive Complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) for Quantification of Left Ventricular Twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Natsuaki, Y., Ennis, D. B. 2014; 39 (2): 339–45

  Abstract

  To evaluate Off Resonance Insensitive Complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) and Fourier Analysis of STimulated echoes (FAST) for the quantification of left ventricular (LV) systolic and diastolic function and compare it with the previously validated FAST+SPAMM technique.LV short-axis tagged images were acquired with ORI-CSPAMM and SPAMM in healthy volunteers (n = 13). The FAST method was used to automatically estimate LV systolic and diastolic twist parameters from rotation of the stimulated echo and stimulated anti-echo about the middle of k-space subsequent to ∼3 min of user interaction.There was no significant difference between measures obtained for FAST+ORI-CSPAMM and FAST+SPAMM for mean peak twist (12.9 ± 3.4° versus 11.9 ± 4.0°; P = 0.4), torsion (3.3 ± 0.9°/cm versus 2.9 ± 1.0°/cm, P = 0.3), circumferential-longitudinal shear angle (9.1 ± 3.0° versus 8.2 ± 3.4°, P = 0.3), twisting rate (79.6 ± 20.2°/s versus 68.2 ± 23.4°/s, P = 0.1), untwisting rate (-117.5 ± 31.4°/s versus -106.6 ± 32.4°/s, P = 0.3), normalized untwisting rate (-9.3 ± 2.0/s versus -9.9 ± 4.4/s, P = 0.7), and time of peak twist (281 ± 18 ms versus 293 ± 25 ms, P = 0.04). FAST+ORI-CSPAMM also provided measures of duration of untwisting (148 ± 21 ms) and the ratio of rapid untwisting to peak twist (0.9 ± 0.3). Bland-Altman analysis of FAST+ORI-CSPAMM and FAST+SPAMM twist data demonstrates excellent agreement with a bias of -0.1° and 95% confidence intervals of (-1.0°, 3.2°).FAST+ORI-CSPAMM is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist and torsion. ORI-CSPAMM corrects off-resonance accrued during tagging preparation and readout and visibly removes chemical shift from the tagging pattern, which confers greater robustness to the derived quantitative measures.

  View details for DOI 10.1002/jmri.24154

  View details for Web of Science ID 000329753400012

  View details for PubMedID 23625854

  View details for PubMedCentralID PMC3732806

• Optimal flip angle for high contrast balanced SSFP cardiac cine imaging. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S., Ennis, D. B. 2014

  Abstract

  To determine the optimal flip angle (FA) for cardiac cine imaging that maximizes myocardial signal and blood-myocardium contrast.Bloch equation simulations of stationary myocardium and flowing blood with an imperfect slice profile were compared to in vivo measurements of blood and myocardium signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) in healthy subjects (N = 10) in the short-axis and four-chamber views and in patients (N = 7) in the three-chamber imaging plane.Left ventricular (LV) and right ventricular (RV) blood SNR and blood-myocardium CNR increases with increasing FA up to ≈105° in the short-axis view. A similar trend is seen in the RV four-chamber view, but a marked SNR difference between the LV and RV blood appears for FA>75°, especially during systole. Notable RV and LV SNR and CNR differences are also evident in the three-chamber view due to the predominant LV in-plane flow versus RV through-plane flow.Very high blood-myocardium CNR can be obtained with a FA of ≈105° in the short-axis plane and ≈75° in the three-chamber and four-chamber imaging planes. However, if through-plane flow is limited, as may occur for patients with low ejection fraction or low heart rates, then the FA may be limited to ≈ 75°. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25228

  View details for PubMedID 24700652

• The effects of noise over the complete space of diffusion tensor shape MEDICAL IMAGE ANALYSIS Gahm, J., Kindlmann, G., Ennis, D. B. 2014; 18 (1): 197–210

  Abstract

  Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique used to quantify the microstructural organization of biological tissues. Multiple images are necessary to reconstruct the tensor data and each acquisition is subject to complex thermal noise. As such, measures of tensor invariants, which characterize components of tensor shape, derived from the tensor data will be biased from their true values. Previous work has examined this bias, but over a narrow range of tensor shape. Herein, we define the mathematics for constructing a tensor from tensor invariants, which permits an intuitive and principled means for building tensors with a complete range of tensor shape and salient microstructural properties. Thereafter, we use this development to evaluate by simulation the effects of noise on characterizing tensor shape over the complete space of tensor shape for three encoding schemes with different SNR and gradient directions. We also define a new framework for determining the distribution of the true values of tensor invariants given their measures, which provides guidance about the confidence the observer should have in the measures. Finally, we present the statistics of tensor invariant estimates over the complete space of tensor shape to demonstrate how the noise sensitivity of tensor invariants varies across the space of tensor shape as well as how the imaging protocol impacts measures of tensor invariants.

  View details for DOI 10.1016/j.media.2013.10.009

  View details for Web of Science ID 000328802900014

  View details for PubMedID 24239734

• A framework for modeling and visualizing cardiovascular deformation under normal and altered circulatory conditions. Studies in health technology and informatics Santhanam, A., Benharash, P., Frank, P., White, B., Min, Y., Ennis, D., Kupelian, P., Dutson, E. 2014; 196: 378–83

  Abstract

  The aim of this paper is to model and visualize cardiovascular deformations in order to better understand vascular movements inside the lung and heart caused by abnormal cardiac conditions. The modeling was performed in two steps: first step involved modeling the cardiac output taking into account of the heart rate and preload blood volume, contractility and systematic vascular resistance. The second step involved deforming a 3D cine cardiac gated Magnetic Resonance Volume to the corresponding cardiac output. Cardiac-gated MR imaging of 4 healthy volunteers were acquired. For each volunteer, a total of 24 short-axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12-15 second breath-hold maneuvers. A 3D multi-resolution optical flow deformable image registration algorithm was used to quantify the volumetric cardiovascular displacements for known cardiac outputs. Results show that a real-time visualization of the vascular deformations inside both the lung as well as the heart can be seen for different cardiac outputs representing normal and abnormal cardiac conditions.

  View details for PubMedID 24732540

• In vivo Confirmation of Hydration Based Contrast Mechanisms for Terahertz Medical Imaging using MRI Bajwa, N., Sung, S., Garritano, J., Nowroozi, B., Tewari, P., Ennis, D. B., Alger, J., Grundfest, W., Taylor, Z., Razeghi, M., Baranov, A. N., Zavada, J. M., Pavlidis, D. SPIE-INT SOC OPTICAL ENGINEERING. 2014

  View details for DOI 10.1117/12.2060115

  View details for Web of Science ID 000348191300020

• Fast 3D T2 -weighted imaging using variable flip angle transition into driven equilibrium (3D T2 -TIDE) balanced SSFP for prostate imaging at 3T. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S., Wu, H. H., Sung, K., Margolis, D. J., Ennis, D. B. 2014

  Abstract

  Three-dimensional (3D) T2 -weighted fast spin echo (FSE) imaging of the prostate currently requires long acquisition times. Our objective was to develop a fast 3D T2 -weighted sequence for prostate imaging at 3T using a variable flip angle transition into driven equilibrium (T2 -TIDE) scheme.3D T2 -TIDE uses interleaved spiral-out phase encode ordering to efficiently sample the ky -kz phase encodes and also uses the transient balanced steady-state free precession signal to acquire the center of k-space for T2 -weighted imaging. Bloch simulations and images from 10 healthy subjects were acquired to evaluate the performance of 3D T2 -TIDE compared to 3D FSE.3D T2 -TIDE images were acquired in 2:54 minutes compared to 7:02 minutes for 3D FSE with identical imaging parameters. The signal-to-noise ratio (SNR) efficiency was significantly higher for 3D T2 -TIDE compared to 3D FSE in nearly all tissues, including periprostatic fat (45 ± 12 vs. 31 ± 7, P < 0.01), gluteal fat (48 ± 8 vs. 41 ± 10, P = 0.12), right peripheral zone (20 ± 4 vs. 16 ± 8, P = 0.12), left peripheral zone (17 ± 2 vs. 12 ± 3, P < 0.01), and anterior fibromuscular stroma (12 ± 4 vs. 4 ± 2, P < 0.01).3D T2 -TIDE images of the prostate can be acquired quickly with SNR efficiency that exceeds that of 3D FSE. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25430

  View details for PubMedID 25195659

• Complementary radial tagging for improved myocardial tagging contrast. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Wang, Z., Nasiraei-Moghaddam, A., Reyhan, M. L., Srinivasan, S., Finn, J. P., Ennis, D. B. 2014

  Abstract

  To develop and evaluate complementary radial tagging (CRT) for improved myocardial tagging contrast.We sought to develop and evaluate CRT, which aims to preserve the radial tag contrast throughout the cardiac cycle. Similar to complementary spatial modulation of magnetization, CRT acquires two sets of images with a phase shift in the tag pattern. The combination of a ramped imaging flip angle and image subtraction enhances tag contrast throughout the cardiac cycle. The proposed CRT technique uses a small table shift away from the isocenter to improve the uniformity of the radial tag pattern. We provide a mathematical solution for the optimal table shift and validate the solution in using a retrospective analysis of images from 500 patients in the Cardiac Atlas Project database.CRT simulations, phantom experiments, and in vivo images all demonstrate the improved tag contrast of CRT compared to RT. The retrospective evaluation demonstrated that acceptable CRT images could be acquired in over 98% of the clinical exams.The CRT technique improves radial tag contrast throughout the cardiac cycle and should produce high quality tag patterns in nearly all patients. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25259

  View details for PubMedID 24824305

• Effect of stellate ganglia stimulation on global and regional left ventricular function as assessed by speckle tracking echocardiography AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Zhou, W., Yamakawa, K., Benharash, P., Ajijola, O., Ennis, D., Hadaya, J., Vaseghi, M., Shivkumar, K., Mahajan, A. 2013; 304 (6): H840–H847

  Abstract

  Left ventricular (LV) twist mechanics and regional strain during cardiac sympathetic efferent activation are poorly understood. The purpose of this study was to compare the effects of left stellate ganglia (LSG) and right stellate ganglia (RSG) stimulation on cardiac twist/untiwst mechanics and regional strain. In nine pigs, echocardiographic imaging and LV pressure-volume measurements were performed before and during unilateral and bilateral stellate ganglion stimulation. LSG and RSG stimulation significantly augmented LV end-systolic pressure by 24% and 22% (P < 0.01), maximal rate of LV pressure change by 167% and 165% (P < 0.01), and time constant of LV relaxation by 20% and 12% (P < 0.01), respectively. RSG stimulation resulted in a greater chronotropic response than LSG stimulation (RSG: 68% vs. LSG: 12%, P < 0.01). Both LSG and RSG stimulation significantly increased global epicardial and endocardial LV rotation and diastolic untwisting rate and reduced the time to peak rotation (P < 0.05). However, LSG stimulation predominantly increased radial and circumferential strain in the LV inferoseptal, inferior, posterior, and lateral regions, whereas RSG stimulation primarily increased radial and circumferential strain in the anteroseptal, anterior, and lateral LV regions. Stimulation of both stellate ganglia led to a uniform increase in all LV segments. Our data suggest that LSG and RSG stimulation lead to a global increase in LV twist, driven by distinct regional strain heterogeneity that may result from myocardial innervation from the LSG and RSG. These findings provide a better understanding of the global and regional functional consequences of regional myocardial innervation from the LSG and RSG.

  View details for DOI 10.1152/ajpheart.00695.2012

  View details for Web of Science ID 000316206400008

  View details for PubMedID 23335795

  View details for PubMedCentralID PMC3602776

• Quantitative assessment of systolic and diastolic left ventricular twist using Fourier Analysis of Stimulated echoes (FAST) and CSPAMM JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Ennis, D. B. 2013; 37 (3): 678–83

  Abstract

  To evaluate Fourier Analysis of Stimulated echoes (FAST) and CSPAMM for the quantification of left ventricular (LV) systolic and diastolic function and compare it with the previously validated FAST+SPAMM technique.LV short-axis tagged images were acquired with CSPAMM and SPAMM in healthy volunteers (n = 13). The FAST method was used to automatically estimate LV systolic and diastolic twist parameters from rotation of the stimulated echo and stimulated anti-echo about the middle of k-space subsequent to ∼3 min of user interaction.There was no significant difference between measures obtained for FAST+CSPAMM and FAST+SPAMM for mean peak twist (13.5 ± 2.7° versus 11.9 ± 4.0°), torsion (3.4 ± 0.8°/cm versus 2.9 ± 1.0°/cm), twisting rate (76.8 ± 22.2°/s versus 68.2 ± 23.4°/s), untwisting rate (-102.7 ± 24.6°/s versus -106.6 ± 32.4°/s), normalized untwisting rate (-7.9 ± 2.2/s versus -9.9 ± 4.4/s), and time of peak twist (279 ± 23 ms versus 293 ± 25 ms) (all P > 0.01). FAST+CSPAMM also provided measures of duration of untwisting (148 ± 21 ms) and the ratio of rapid untwist to peak twist (0.8 ± 0.3). Bland-Altman analysis of FAST+CSPAMM and FAST+SPAMM twist data demonstrates excellent agreement with a bias of 1.1° and 95% confidence intervals of [-3.3°, 5.2°].FAST+CSPAMM is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist and torsion.

  View details for DOI 10.1002/jmri.23849

  View details for Web of Science ID 000315220000015

  View details for PubMedID 23371791

  View details for PubMedCentralID PMC3578174

• Chemical shift-induced phase errors in phase-contrast MRI MAGNETIC RESONANCE IN MEDICINE Middione, M. J., Ennis, D. B. 2013; 69 (2): 391–401

  Abstract

  Phase-contrast magnetic resonance imaging is subject to numerous sources of error, which decrease clinical confidence in the reported measures. This work outlines how stationary perivascular fat can impart a significant chemical shift induced phase-contrast magnetic resonance imaging measurement error using computational simulations, in vitro, and in vivo experiments. This chemical shift error does not subtract in phase difference processing, but can be minimized with proper parameter selection. The chemical shift induced phase errors largely depend on both the receiver bandwidth and the TE. Both theory and an in vivo comparison of the maximum difference in net forward flow between vessels with and without perivascular fat indicated that the effects of chemically shifted perivascular fat are minimized by the use of high bandwidth (814 Hz/px) and an in-phase TE (high BW-TE(IN)). In healthy volunteers (N = 10) high BW-TE(IN) significantly improves intrapatient net forward flow agreement compared with low bandwidth (401 Hz/px) and a mid-phase TE as indicated by significantly decreased measurement biases and limits of agreement for the ascending aorta (1.8 ± 0.5 mL vs. 6.4 ± 2.8 mL, P = 0.01), main pulmonary artery (2.0 ± 0.9 mL vs. 11.9 ± 5.8 mL, P = 0.04), the left pulmonary artery (1.3 ± 0.9 mL vs. 5.4 ± 2.5 mL, P = 0.003), and all vessels (1.7 ± 0.8 mL vs. 7.2 ± 4.4 mL, P = 0.001).

  View details for DOI 10.1002/mrm.24262

  View details for Web of Science ID 000314059500011

  View details for PubMedID 22488490

  View details for PubMedCentralID PMC3396715

• Variable flip angle balanced steady-state free precession for lower SAR or higher contrast cardiac cine imaging. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Srinivasan, S., Ennis, D. B. 2013

  Abstract

  PURPOSE: Cardiac cine balanced steady-state free precession (bSSFP) imaging uses a high flip angle (FA) to obtain high blood-myocardium signal-to-noise and contrast-to-noise ratios (CNR). Use of high FAs, however, results in substantially increased SAR. Our objective was to develop a variable FA bSSFP cardiac cine imaging technique with: (1) low SAR and blood-myocardium CNR similar to conventional constant FA bSSFP (CFA-bSSFP) or (2) increased blood-myocardium CNR compared to CFA-bSSFP with similar SAR. METHODS: Variable FA bSSFP cardiac cine imaging was achieved using an asynchronous k-space acquisition, which is asynchronous to the cardiac cycle (aVFA-bSSFP). Bloch simulations and phantom experiments were performed to compare the signal, resolution, and frequency response of the variable FA bSSFP and CFA-bSSFP schemes. Ten volunteers were imaged with different aVFA-bSSFP and asynchronous CFA-bSSFP schemes and compared to conventional segmented CFA-bSSFP. RESULTS: The SAR of aVFA-bSSFP is significantly decreased by 36% compared to asynchronous CFA-bSSFP (1.9 ± 0.2 vs. 3.0 ± 0.2 W/kg, P <  10(-10) ) for similar blood-myocardium CNR (34 ± 6 vs. 35 ± 9, P = 0.5). Alternately, the CNR of the aVFA-bSSFP is improved by 28% compared to asynchronous CFA-bSSFP (49 ± 9 vs. 38 ± 8, P <  10(-4) ) with similar SAR (3.2 ± 0.5 vs. 3.3 ± 0.5 W/kg, P = 0.6). CONCLUSION: aVFA-bSSFP can be used for lower SAR or higher contrast cardiac cine imaging compared to the conventional segmented CFA-bSSFP imaging. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24764

  View details for PubMedID 23629954

• Multi-scale, multi-modal image integration for image-guided clinical interventions in the head and neck anatomy. Studies in health technology and informatics Santhanam, A. P., Dou, T., Neylon, J., Min, Y., Kupelian, A., Sheng, K., Ennis, D., Rolland, J., Low, D., Kupelian, P. 2013; 184: 380–86

  Abstract

  The aim of this paper is to enable model guided multi-scale and multi-modal image integration for the head and neck anatomy. The image modality used for this purpose includes multi-pose Magnetic Resonance Imaging (MRI), Mega Voltage CT, and hand-held Optical Coherence Tomography. A biomechanical model that incorporates subject-specific young's modulus and shear modulus properties is developed from multi-pose MRI, positioned in the treatment setup using Mega Voltage CT (MVCT), and actuated using multiple kinect surface cameras to mimic patient postures during Optical Coherence Microscopy (OCM) imaging. Two different 3D tracking mechanisms were employed for aligning the patient surface and the probe position to the MRI data. The results show the accuracy of the two tracking algorithms and the 3D head and neck deformation representing the multiple poses, the subject will take during the OCM imaging.

  View details for PubMedID 23400188

• WEIGHTED COMPONENT-BASED TENSOR DISTANCE APPLIED TO GRAPH-BASED SEGMENTATION OF CARDIAC DT-MRI Gahm, J., Kung, G. L., Ennis, D. B., IEEE IEEE. 2013: 504–7

  View details for Web of Science ID 000326900100126

• Injection of gadolinium contrast through pediatric central venous catheters: a safety study PEDIATRIC RADIOLOGY Moriarty, J. M., Kung, G. L., Ramos, Y., Moghaddam, A. N., Ennis, D. B., Finn, J. 2012; 42 (9): 1064–69

  Abstract

  Catheter rupture during CT angiography has prompted policies prohibiting the use of electronic injectors with peripherally inserted central venous catheters (PICCs) not only for CT but also for MRI. Consequently, many institutions mandate hand injection for MR angiography, limiting precision of infusion rates and durations of delivery.To determine whether electronic injection of gadolinium-based contrast media through a range of small-caliber, single-lumen PICCs would be safe without risk of catheter rupture over the range of clinical protocols and determine whether programmed flow rates and volumes were realized when using PICCs for contrast delivery.Experiments were performed and recorded using the Medrad Spectris Solaris EP MR Injection System. PICC sizes, contrast media and flow rates were based on common institutional protocols.No catheters were damaged during any experiments. Mean difference between programmed and delivered volume was 0.07 ± 0.10 mL for all experiments. Reduced flow rates and prolonged injection durations were observed when the injector's pressure-limiting algorithm was triggered, only in protocols outside the clinical range.PICCs commonly used in children can withstand in vitro power injection of gadolinium-based contrast media at protocols significantly above clinical levels.

  View details for DOI 10.1007/s00247-012-2397-z

  View details for Web of Science ID 000307717800004

  View details for PubMedID 22526282

• The dependence of radiofrequency induced pacemaker lead tip heating on the electrical conductivity of the medium at the lead tip MAGNETIC RESONANCE IN MEDICINE Langman, D. A., Goldberg, I. B., Judy, J., Finn, J., Ennis, D. B. 2012; 68 (2): 606–13

  Abstract

  Radiofrequency induced pacemaker lead tip heating is one of the main reasons magnetic resonance imaging (MRI) is contraindicated for patients with pacemakers. The objective of this work was to evaluate the dependence of pacemaker lead tip heating during MRI scanning on the electrical conductivity of the medium surrounding the pacemaker lead tip. The effect of conductivity was measured using hydroxyethyl cellulose, polyacrylic acid, and saline with conductivities ranging from 0 to 3 S/m which spans the range of human tissue conductivity. The maximum lead tip heating observed in polyacrylic acid was 50.4 °C at 0.28 S/m, in hydroxyethyl cellulose the maximum was 36.8 °C at 0.52 S/m, and in saline the maximum was 12.5 °C at 0.51 S/m. The maximum power transfer theorem was used to calculate the relative power deposited in the solution based on the characteristic impedance of the pacemaker lead and test solution impedance. The results demonstrate a strong correlation between the relative power deposited and pacemaker lead tip heating for hydroxyethyl cellulose and saline solutions. Maximum power deposition occurred when the impedance of the solution matched the pacemaker lead impedance. Pacemaker lead tip heating is dependent upon the electrical conductivity of the solution at the lead tip and should be considered when planning in vitro gel or saline experiments.

  View details for DOI 10.1002/mrm.23235

  View details for Web of Science ID 000306318900034

  View details for PubMedID 22213610

• Fourier analysis of STimulated echoes (FAST) for the quantitative analysis of left ventricular twist JOURNAL OF MAGNETIC RESONANCE IMAGING Reyhan, M., Natsuaki, Y., Ennis, D. B. 2012; 35 (3): 587–93

  Abstract

  To validate a novel method for the rapid and facile quantification of left ventricular (LV) twist from tagged magnetic resonance images and demonstrate the potential clinical utility in a series of 20 healthy volunteers.Cardiac magnetic resonance imaging (MRI) short-axis images were acquired with tissue tagging in 20 healthy subjects and six canines. The tagged images were processed using a novel Fourier Analysis of the STimulated echoes (FAST) method, which uses a series of Fourier-space operations to measure LV twist with limited user interaction. A subset of eight healthy subjects and the canine data were compared to results from previously validated "gold standard" software (FindTags). Interobserver and intraobserver coefficients of variation (CV(INTER) and CV(INTRA) ), linear regression, and Bland-Altman analyses were used to assess agreement between observers and methods.CV(INTRA) for peak systolic twist (2.9% and 2.6%) and CV(INTER) (4.3% and 4.2%) were all small. Linear regression analysis of the FAST and FindTags twist values indicated very good agreement in healthy subjects (R = 0.91) and in canines (R = 0.95). Bland-Altman comparison of the FAST and FindTags twist results indicated excellent agreement in healthy subjects (bias of -0.5°, 95% confidence intervals (-4.3°, 4.3°)) and canines (bias of 0.2°, 95% confidence intervals (-2.7°, 3.1°)). Peak systolic twist in healthy subjects averaged 10.5 ± 1.9° degrees.The FAST method for quantifying LV twist produces results that are not significantly different from the current "gold standard" in a fraction of the user interaction time and has demonstrated feasibility in human subjects.

  View details for DOI 10.1002/jmri.22863

  View details for Web of Science ID 000300690400012

  View details for PubMedID 22069227

  View details for PubMedCentralID PMC3288273

• Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Itoh, A., Stephens, E. H., Ennis, D. B., Carlhall, C., Bothe, W., Nguyen, T. C., Swanson, J. C., Miller, D. C., Ingels, N. B. 2012; 302 (1): H180-H187

  Abstract

  Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.

  View details for DOI 10.1152/ajpheart.00687.2011

  View details for PubMedID 22037187

• 3D Reconstruction and Image Fusion using Transurethral Ultrasound Natarajan, S., Culjat, M., Singh, R., Ennis, D., Marks, L., Grundfest, W. S., IEEE IEEE. 2012: 138–41

  View details for DOI 10.1109/ULTSYM.2012.0034

  View details for Web of Science ID 000326960200030

• The Presence of Two Local Myocardial Sheet Populations Confirmed by Diffusion Tensor MRI and Histological Validation JOURNAL OF MAGNETIC RESONANCE IMAGING Kung, G. L., Tom C Nguyen, T. C., Itoh, A., Skare, S., Ingels, N. B., Miller, D. C., Ennis, D. B. 2011; 34 (5): 1080-1091

  Abstract

  To establish the correspondence between the two histologically observable and diffusion tensor MRI (DTMRI) measurements of myolaminae orientation for the first time and show that single myolaminar orientations observed in local histology may result from histological artifact.DTMRI was performed on six sheep left ventricles (LV), then corresponding direct histological transmural measurements were made within the anterobasal and lateral-equatorial LV. Secondary and tertiary eigenvectors of the diffusion tensor were compared with each of the two locally observable sheet orientations from histology. Diffusion tensor invariants were calculated to compare differences in microstructural diffusive properties between histological locations with one observable sheet population and two observable sheet populations.Mean difference ± 1SD between DTMRI and histology measured sheet angles was 8° ± 27°. Diffusion tensor invariants showed no significant differences between histological locations with one observable sheet population and locations with two observable sheet populations.DTMRI measurements of myolaminae orientations derived from the secondary and tertiary eigenvectors correspond to each of the two local myolaminae orientations observed in histology. Two local sheet populations may exist throughout LV myocardium, and one local sheet population observed in histology may be a result of preparation artifact.

  View details for DOI 10.1002/jmri.22725

  View details for Web of Science ID 000296206900011

  View details for PubMedID 21932362

  View details for PubMedCentralID PMC3195899

• Pacemaker Lead Tip Heating in Abandoned and Pacemaker-Attached Leads at 1.5 Tesla MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Langman, D. A., Goldberg, I. B., Finn, J., Ennis, D. B. 2011; 33 (2): 426–31

  Abstract

  To assess the risk of RF-induced heating in pacemaker-attached and abandoned leads using in vitro temperature measurements at 1.5 Tesla as a function of lead length.Five custom lead lengths, 20-60 cm, were exposed to a uniform magnitude and phase radiofrequency electric field to examine the effect of lead length on pacemaker lead tip heating for pacemaker-attached and abandoned pacemaker leads.Abandoned and pacemaker-attached leads show resonant heating behavior and maximum heating occurs at different lead lengths due to the differences in termination conditions. For clinical lead lengths (40-60 cm) abandoned leads exhibited greater lead tip heating compared with pacemaker-attached leads.Current recommendations for MRI pacemaker safety should highlight the possible increased risk for patients with abandoned leads as compared to pacemaker-attached leads.

  View details for DOI 10.1002/jmri.22463

  View details for Web of Science ID 000286953300019

  View details for PubMedID 21274985

• Analytical method to measure three-dimensional strain patterns in the left ventricle from single slice displacement data JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE Moghaddam, A., Saber, N. R., Wen, H., Finn, J., Ennis, D. B., Gharib, M. 2010; 12: 33

  Abstract

  Displacement encoded Cardiovascular MR (CMR) can provide high spatial resolution measurements of three-dimensional (3D) Lagrangian displacement. Spatial gradients of the Lagrangian displacement field are used to measure regional myocardial strain. In general, adjacent parallel slices are needed in order to calculate the spatial gradient in the through-slice direction. This necessitates the acquisition of additional data and prolongs the scan time. The goal of this study is to define an analytic solution that supports the reconstruction of the out-of-plane components of the Lagrangian strain tensor in addition to the in-plane components from a single-slice displacement CMR dataset with high spatio-temporal resolution. The technique assumes incompressibility of the myocardium as a physical constraint.The feasibility of the method is demonstrated in a healthy human subject and the results are compared to those of other studies. The proposed method was validated with simulated data and strain estimates from experimentally measured DENSE data, which were compared to the strain calculation from a conventional two-slice acquisition.This analytical method reduces the need to acquire data from adjacent slices when calculating regional Lagrangian strains and can effectively reduce the long scan time by a factor of two.

  View details for DOI 10.1186/1532-429X-12-33

  View details for Web of Science ID 000280092400001

  View details for PubMedID 20515489

  View details for PubMedCentralID PMC2903580

• Cardiac Active Contraction Parameters Estimated from Magnetic Resonance Imaging Wang, V. Y., Lam, H. I., Ennis, D. B., Cowan, B. R., Young, A. A., Nash, M. P., Camara, O., Pop, M., Rhode, K., Sermesant, M., Smith, N., Young, A. SPRINGER-VERLAG BERLIN. 2010: 194-+

  View details for Web of Science ID 000288721700020

• Mitral annular hinge motion contribution to changes in mitral septal-lateral dimension and annular area 88th Annual Meeting of the American-Association-for-Thoracic-Surgery Itoh, A., Ennis, D. B., Bothe, W., Swanson, J. C., Krishnamurthy, G., Nguyen, T. C., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2009: 1090–99

  Abstract

  The mitral annulus is a dynamic, saddle-shaped structure consisting of fibrous and muscular regions. Normal physiologic mechanisms of annular motion are incompletely understood, and more complete characterization is needed to provide rational basis for annuloplasty ring design and to enhance clinical outcomes.Seventeen sheep had radiopaque markers implanted; 16 around the annulus and 2 on middle anterior and posterior leaflet edges. Four-dimensional marker coordinates were acquired with biplanar videofluoroscopy at 60 Hz. Hinge angle was quantified between fibrous and muscular annular planes, with 0 degrees defined at end diastole, to characterize its contribution to alterations in mitral septal-lateral dimension and 2-dimensional total annular area throughout the cardiac cycle.During isovolumic contraction (pre-ejection), hinge angle abruptly increased, reaching maximum (steepest saddle shape, change 18 degrees +/- 13 degrees ) at peak left ventricular pressure. During ejection, hinge angle did not change; it then decreased during early filling (change 2 degrees +/- 2 degrees ). Septal-lateral dimension and total area paralleled hinge angle dynamics and leaflet distance (anterior to posterior marker). Pre-ejection septal-lateral reduction was 13% +/- 7% (3.3 +/- 1.5 mm) from 9% muscular dimension fall and 18 degrees +/- 13 degrees hinge angle increase.Pre-ejection increase in hinge angle contributes substantially to septal-lateral and total area reduction, facilitating leaflet coaptation. Semirigid annuloplasty rings or partial bands may preserve hinge motion, but possible recurrent annular dilatation could result in recurrent mitral regurgitation. Long-term clinical studies are required to determine who might benefit most from preserving intrinsic hinge motion without compromising repair durability.

  View details for DOI 10.1016/j.jtcvs.2009.03.067

  View details for PubMedID 19747697

• Regional Mitral Leaflet Opening During Acute Ischemic Mitral Regurgitation 4th Biennial Meeting of the Society-for-Heart-Valve-Disease Bothe, W., Ennis, D. B., Carlhall, C. J., Nguyen, T. C., Timek, T. A., Lai, D. T., Itoh, A., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2009: 586–96

  Abstract

  Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics were quantified along the entire valvular coaptation line in an ovine model of acute IMR.Ten radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 +/- 0.3 versus 2.3 +/- 0.7, p < 0.05), decreased contractility (dP/dt(max): 1,948 +/- 598 versus 1,119 +/- 293 mmHg/s, p < 0.05), and slower left ventricular relaxation rate (dP/dt(min): -1,079 +/- 188 versus -538 +/- 147 mmHg/s, p < 0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 +/- 28 versus 83 +/- 43 ms, B1/B2: 105 +/- 32 versus 68 +/- 35 ms, C1/C2: 126 +/- 25 versus 74 +/- 37 ms, D1/D2: 114 +/- 28 versus 71 +/- 34 ms, E1/E2: 125 +/- 29 versus 105 +/- 33 ms; all p < 0.05) and was slower (A1/A2: 16.8 +/- 9.6 versus 14.2 +/- 9.4 cm/s, B1/B2: 40.4 +/- 9.9 versus 32.2 +/- 10.0 cm/s, C1/C2: 59.0 +/- 14.9 versus 50.4 +/- 18.1 cm/s, D1/D2: 34.4 +/- 10.4 versus 25.5 +/- 10.9 cm/s; all p < 0.05), except at the posterior edge (E1/E2: 13.3 +/- 8.7 versus 10.6 +/- 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

  View details for PubMedID 20099707

• Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function Wang, V. Y., Lam, H. I., Ennis, D. B., Cowan, B. R., Young, A. A., Nash, M. P. ELSEVIER SCIENCE BV. 2009: 773–84

  Abstract

  The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

  View details for DOI 10.1016/j.media.2009.07.006

  View details for Web of Science ID 000270264200008

  View details for PubMedID 19664952

• Active stiffening of mitral valve leaflets in the beating heart AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Itoh, A., Krishnamurthy, G., Swanson, J. C., Ennis, D. B., Bothe, W., Kuhl, E., Karlsson, M., Davis, L. R., Miller, D. C., Ingels, N. B. 2009; 296 (6): H1766-H1773

  Abstract

  The anterior leaflet of the mitral valve (MV), viewed traditionally as a passive membrane, is shown to be a highly active structure in the beating heart. Two types of leaflet contractile activity are demonstrated: 1) a brief twitch at the beginning of each beat (reflecting contraction of myocytes in the leaflet in communication with and excited by left atrial muscle) that is relaxed by midsystole and whose contractile activity is eliminated with beta-receptor blockade and 2) sustained tone during isovolumic relaxation, insensitive to beta-blockade, but doubled by stimulation of the neurally rich region of aortic-mitral continuity. These findings raise the possibility that these leaflets are neurally controlled tissues, with potentially adaptive capabilities to meet the changing physiological demands on the heart. They also provide a basis for a permanent paradigm shift from one viewing the leaflets as passive flaps to one viewing them as active tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to MV disease, but even the definitions of MV disease itself.

  View details for DOI 10.1152/ajpheart.00120.2009

  View details for PubMedID 19363135

• Reduced Systolic Torsion in Chronic "Pure" Mitral Regurgitation CIRCULATION-CARDIOVASCULAR IMAGING Ennis, D. B., Nguyen, T. C., Itoh, A., Bothe, W., Liang, D. H., Ingels, N. B., Miller, D. C. 2009; 2 (2): 85-92

  Abstract

  Global left ventricular (LV) torsion declines with chronic ischemic mitral regurgitation (MR), which may accelerate the LV remodeling spiral toward global cardiomyopathy; however, it has not been definitively established whether this torsional decline is attributable to the infarct, the MR, or their combined effect. We tested the hypothesis that chronic "pure" MR alone reduces global LV torsion.Chronic "pure" MR was created in 13 sheep by surgically punching a 3.5- to 4.8-mm hole (HOLE) in the mitral valve posterior leaflet. Nine control (CNTL) sheep were operated on concurrently. At 1 (WK-01) and 12 weeks (WK-12) postoperatively, the 4D motion of implanted radiopaque markers was used to calculate global LV torsion. MR-grade in HOLE was greater than CNTL at WK-01 and WK-12 (2.5+/-1.1 versus 0.6+/-0.5, P<0.001 at WK-12). HOLE LV mass index was larger at WK-12 compared with CNTL (195+/-14 versus 170+/-17 g/m(2), P<0.01), indicating LV remodeling. Global LV systolic torsion decreased in HOLE from WK-01 to WK-12 (4.1+/-2.8 degrees versus 1.7+/-1.7 degrees , P<0.01), but did not change in CNTL (5.5+/-1.8 degrees versus 4.2+/-2.7 degrees , P=NS). Global LV torsion was lower in HOLE relative to CNTL at WK-12 (P<0.05) but not at WK-01 (P=NS).Twelve weeks of chronic "pure" MR resulting in mild global LV remodeling is associated with significantly increased LV mass index and reduced global LV systolic torsion, but no other significant changes in hemodynamics. MR alone is a major component of torsional deterioration in "pure" MR and may be an important factor in chronic ischemic mitral regurgitation.

  View details for DOI 10.1161/CIRCIMAGING.108.785923

  View details for PubMedID 19808573

• QUANTIFICATION OF IN VIVO STRESSES IN THE OVINE ANTERIOR MITRAL VALVE LEAFLET ASME Summer Bioengineering Conference Krishnamurthy, G., Ltoh, A., Bothe, W., Ennis, D. B., Swanson, J. C., Kuhl, E., Miller, D. C., Ingels, N. B. AMER SOC MECHANICAL ENGINEERS. 2009: 131–132

  View details for Web of Science ID 000263364700066

• Myofiber angle distributions in the ovine left Ventricle do not conform to computationally optimized predictions JOURNAL OF BIOMECHANICS Ennis, D. B., Nguyen, T. C., Riboh, J. C., Wigstroem, L., Harrington, K. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2008; 41 (15): 3219-3224

  Abstract

  Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.

  View details for DOI 10.1016/j.jbiomech.2008.08.007

  View details for PubMedID 18805536

• Alterations in transmural myocardial strain - An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Carlhaell, C. J., Nguyen, T. C., Itoh, A., Ennis, D. B., Bothe, W., Liang, D., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2008: S256–S262

  Abstract

  In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model.Sheep were randomized to control (CTRL, n=8) or experimental (EXP, n=12) groups. In EXP, a 3.5- or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2]; 3.0 [1-4] versus 0.5 [0-1], respectively, both P<0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201+/-18 versus 173+/-17 g/m(2); P<0.01). LVEDVI increased in EXP from 1 to 12 weeks (P=0.015). Between the 1 and 12 week values, the change in BNP (-4.5+/-4.4 versus -3.0+/-3.6 pmol/L), PRSW (9+/-13 versus 23+/-18 mm Hg), tau (-3+/-11 versus -4+/-7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral: -0.08+/-0.05 versus 0.02+/-0.14; anterior: -0.10+/-0.05 versus -0.02+/-0.07, both P<0.01).Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.

  View details for DOI 10.1161/CIRCULATIONAHA.107.753525

  View details for PubMedID 18824764

• The effect of pure mitral regurgitation on mitral annular geometry and three-dimensional saddle shape 87th Annual Meeting of the American-Association-for-Thoracic-Surgery Nguyen, T. C., Itoh, A., Carlhall, C. J., Bothe, W., Timek, T. A., Ennis, D. B., Oakes, R. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2008: 557–65

  Abstract

  Chronic ischemic mitral regurgitation is associated with mitral annular dilatation in the septal-lateral dimension and flattening of the annular 3-dimensional saddle shape. To examine whether these perturbations are caused by the ischemic insult, mitral regurgitation, or both, we investigated the effects of pure mitral regurgitation (low pressure volume overload) on annular geometry and shape.Eight radiopaque markers were sutured evenly around the mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral annular area, annular septal-lateral and commissure-commissure dimensions, and annular height were calculated every 16.7 ms.Mitral regurgitation grade was 0.4 +/- 0.4 in CTRL and 3.0 +/- 0.8 in HOLE (P < .001) at 12 weeks. End-diastolic left ventricular volume index was greater in HOLE at both 1 and 12 weeks; end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular area increased in HOLE predominantly in the commissure-commissure dimension, with no difference in annular height between HOLE versus CTRL at 1 or 12 weeks, respectively.In contrast with annular septal-lateral dilatation and flattening of the annular saddle shape observed with chronic ischemic mitral regurgitation, pure mitral regurgitation was associated with commissure-commissure dimension annular dilatation and no change in annular shape. Thus, infarction is a more important determinant of septal-lateral dilatation and annular shape than mitral regurgitation, which reinforces the need for disease-specific designs of annuloplasty rings.

  View details for DOI 10.1016/j.jtcvs.2007.12.087

  View details for PubMedID 18805251

• Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Krishnamurthy, G., Ennis, D. B., Itoh, A., Bothe, W., Swanson, J. C., Karlsson, M., Kuhl, E., Miller, D. C., Ingels, N. B. 2008; 295 (3): H1141-H1149

  Abstract

  We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR; when the pressure difference across the valve is approximately 0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure-commisure (E(circ)) and radial (E(rad)) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/- 18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves.

  View details for DOI 10.1152/ajpheart.00284.2008

  View details for PubMedID 18621858

• Non-uniform transmural remodeling in ovine chronic mitral regurgitation Ennis, D. B., Nguyen, T. C., Itoh, A., Carlhaell, C. J., Oakes, R. A., Bothe, W., Liang, D., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2008

  View details for Web of Science ID 000208467801528

• Effects of acute ischemic mitral regurgitation on three-dimensional mitral leaflet edge geometry 21st Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Bothe, W., Nguyen, T. C., Ennis, D. B., Itoh, A., Carlhall, C. J., Lai, D. T., Ingels, N. B., Miller, D. C. OXFORD UNIV PRESS INC. 2008: 191–97

  Abstract

  Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction.Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A(1)-E(1)) and posterior (A(2)-E(2)) mitral leaflet free edges from the anterior commissure (A(1)-A(2)) to the posterior commissure (E(1)-E(2)). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS.Acute ischemia increased echocardiographic MR grade (0.5+/-0.3 vs 2.3+/-0.7, p<0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7+/-10 vs 22+/-19 mm(2), 1+/-2 vs 18+/-16 mm(2), 0 vs 17+/-15 mm(2)); Mid-MOA (9+/-13 vs 25+/-17 mm(2), 3+/-6 vs 21+/-19 mm(2), 0 vs 25+/-17 mm(2)); and Post-MOA (8+/-10 vs 25+/-16, 2+/-4 vs 22+/-13 mm(2), 0 vs 23+/-13 mm(2)), all p<0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B(1)-B(2): 7.1+/-1.8mm vs 7.9+/-1.7 mm, C(1)-C(2): 6.9+/-1.3mm vs 8.0+/-1.5mm, both p<0.05).MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.

  View details for DOI 10.1016/j.ejcts.2007.10.024

  View details for PubMedID 18321461

• Diffusion tensor analysis with invariant gradients and rotation tangents IEEE TRANSACTIONS ON MEDICAL IMAGING Kindlmann, G., Ennis, D. B., Whitaker, R. T., Westin, C. 2007; 26 (11): 1483-1499

  Abstract

  Guided by empirically established connections between clinically important tissue properties and diffusion tensor parameters, we introduce a framework for decomposing variations in diffusion tensors into changes in shape and orientation. Tensor shape and orientation both have three degrees-of-freedom, spanned by invariant gradients and rotation tangents, respectively. As an initial demonstration of the framework, we create a tunable measure of tensor difference that can selectively respond to shape and orientation. Second, to analyze the spatial gradient in a tensor volume (a third-order tensor), our framework generates edge strength measures that can discriminate between different neuroanatomical boundaries, as well as creating a novel detector of white matter tracts that are adjacent yet distinctly oriented. Finally, we apply the framework to decompose the fourth-order diffusion covariance tensor into individual and aggregate measures of shape and orientation covariance, including a direct approximation for the variance of tensor invariants such as fractional anisotropy.

  View details for DOI 10.1109/TMI.2007.907277

  View details for Web of Science ID 000250897700008

  View details for PubMedID 18041264

• Alterations in transmural myocardial strain: An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Nguyen, T. C., Carlhall, C. J., Itoh, A., Oakes, R. A., Ennis, D. B., Bothe, W., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2007: 368–68

  View details for Web of Science ID 000250394301667

• Altered myocardial shear strains are associated with chronic ischemic mitral regurgitation 42nd Annual Meeting of the Society-of-Thoracic-Surgeons Nguyen, T. C., Cheng, A., Langer, F., Rodriguez, F., Oakes, R. A., Itoh, A., Ennis, D. B., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2007: 47–54

  Abstract

  Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains.Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening.Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+).An equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with unchanged ED and end-systolic remodeling strains as well as systolic circumferential, longitudinal, and radial strains, argue against a global LV or regional myocardial geometric basis for the cardiomyopathy associated with IMR. Further, similar systolic fiber shortening in both groups militates against an intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton and extracellular-matrix) interactions.

  View details for DOI 10.1016/j.athoracsur.2006.08.039

  View details for PubMedID 17184629

• Dobutamine myocardial strain rate response is transmurally inhomogeneous 79th Annual Scientific Session of the American-Heart-Association Itoh, A., Nguyen, T. C., Cheng, A., Oakes, R. A., Ennis, D. B., Kameda, Y., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: 570–70

  View details for Web of Science ID 000241792803565

• Detection of myocardial capillary orientation with intravascular iron-oxide nanoparticles in spin-echo MRI MAGNETIC RESONANCE IN MEDICINE Vignaud, A., Rodriguez, Ennis, D. B., DeSilva, R., Kellman, P., Taylor, J., Bennett, E., Wen, H. 2006; 55 (4): 725–30

  Abstract

  In mammalian hearts the capillaries are closely aligned with the muscle fibers. We report our observation of a main-field direction-dependent contrast in MR spin-echo (SE) images of the heart in the presence of Ferumoxtran-10, an intravascular iron-oxide nanoparticle contrast agent (CA). We describe a novel MRI method for mapping the preferential orientation of capillaries in the myocardial wall. The eigenvector corresponding to the minimum eigen value of the R2 relaxation rate tensor is consistent with the expected orientation of the capillary network. Preliminary results also demonstrate the feasibility of this method for in vivo application to rodent imaging.

  View details for DOI 10.1002/mrm.20827

  View details for Web of Science ID 000236602700003

  View details for PubMedID 16506158

  View details for PubMedCentralID PMC2881601

• The visible heart - Analysis of myocardial fiber structure using three-dimensional histology Experimental Biology 2006 Annual Meeting Wigstrom, L., Ennis, D. B., Nguyen, T. C., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1198–A1198

  View details for Web of Science ID 000236326203229

• Regional heterogeneity of myofiber orientation in the ovine left ventricle Nquyen, T. C., Ennis, D. B., Riboh, J. C., Harrington, K. B., Wigstrom, L., Daughter, G. T., Miller, C. D., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1195

  View details for Web of Science ID 000236326203216

• Transmural left ventricular shear strain alterations adjacent to and remote from infarcted myocardium JOURNAL OF HEART VALVE DISEASE Cheng, A., Langer, F., Nguyen, T. C., Malinowski, M., Ennis, D. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2006; 15 (2): 209-218

  Abstract

  In some patients, dysfunction in a localized infarct region spreads throughout the left ventricle to aggravate mitral regurgitation and produce deleterious global left ventricular (LV) remodeling. Alterations in transmural strains could be a trigger for this process, as these changes can produce apoptosis and extracellular matrix disruption. The hypothesis was tested that localized infarction perturbs transmural strain patterns not only in adjacent regions but also at remote sites.Transmural radiopaque beadsets were inserted surgically into the anterior basal and lateral equatorial LV walls of 25 sheep; additional markers were used to silhouette the left ventricle. One week thereafter, 10 sheep had posterior wall infarction from (obtuse marginal occlusion, INFARCT) and 15 had no infarction (SHAM). Four-dimensional marker dynamics were studied with biplane videofluoroscopy eight weeks later. Fractional area shrinkage, LV volumes and transmural circumferential, longitudinal and radial systolic strains were analyzed.Compared to SHAM, INFARCT greatly increased longitudinal-radial shear (mid-wall: 0.07 +/- 0.07 versus 0.14 +/- 0.06; subendocardium: 0.03 +/- 0.07 versus 0.20 +/- 0.08) in the inner half of the lateral LV wall and increased circumferential-radial shear (mid-wall: 0.03 +/- 0.05 versus 0.10 +/- 0.04; subepicardium: 0.02 +/- 0.05 versus 0.12 +/- 0.10) increased in the outer half of the LATERAL wall. In the ANTERIOR wall, INFARCT also increased longitudinal-radial shear (midwall: 0.01 +/- 0.05 versus 0.12 +/- 0.04; subendocardium: 0.04 +/- 0.09 versus 0.25 +/- 0.20) in the inner layers.Increased transmural shear strains were found not only in an adjacent region, but also at a site remote from a localized infarction. This perturbation could trigger remodeling processes that promote the progression of ischemic cardiomyopathy. A better understanding of this process is important for the future development of surgical therapies to reverse destructive LV remodeling.

  View details for PubMedID 16607903

• Noninvasive measurement of myocardial tissue volume change during systolic contraction and diastolic relaxation in the canine left ventricle MAGNETIC RESONANCE IN MEDICINE Rodriguez, Ennis, D. B., Wen, H. 2006; 55 (3): 484–90

  Abstract

  In coronary circulation the flow in epicardial arteries and veins is observed to be pulsatile and out of phase with each other. Theoretical considerations predict that this phenomenon extends to all levels of the vascular tree and leads to a cyclic fluctuation of regional tissue volume. Intramyocardial tissue volume change between end-systole and end-diastole was measured noninvasively with MRI in 10 closed-chest beagles. The displacement encoding with stimulated-echo technique was used to obtain pixel-by-pixel tissue displacement field between end-diastole and end-systole and vice versa in the midlevel left ventricle, from which the 3D strain matrix and volume changes were calculated. The volume change was between 0.8+/-0.5% (mean+/-STD) in the epicardial layer and 1.5+/-0.6% in the subendocardial layer of the left ventricle. Tissue volume fluctuation reflects the amount of arterial inflow in a heartbeat under the assumption that regional arterial inflow and venous outflow have little time overlap. The corresponding perfusion level was estimated to be from (1.0+/-0.6) ml/min/g in the epicardial layer to (1.7+/-0.6) ml/min/g in the subendocardial layer, in good agreement with microsphere measurements in the same dog model. The result supports the notion of high arterial resistance at the microvascular level from intramyocardial pressure during systole.

  View details for DOI 10.1002/mrm.20786

  View details for Web of Science ID 000235858400004

  View details for PubMedID 16408273

  View details for PubMedCentralID PMC2887312

• Evidence of structural remodeling in the dyssynchronous failing heart CIRCULATION RESEARCH Helm, P. A., Younes, L., Beg, M. F., Ennis, D. B., Leclercq, C., Faris, O. P., McVeigh, E., Kass, D., Miller, M. I., Winslow, R. L. 2006; 98 (1): 125–32

  Abstract

  Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state. We apply novel computational methods to identify statistically significant changes of cardiac anatomic structure in the failing and control heart populations. The results demonstrate significant regional differences in geometric remodeling in the dyssynchronous failing heart versus control. Ventricular chamber dilatation and reduction in wall thickness in septal and some posterior and anterior regions are observed. Primary fiber orientation showed no significant change. However, this result coupled with the local wall thinning in the septum implies an altered transmural fiber gradient. Further, we observe that orientation of laminar sheets become more vertical in the early-activated septum, with no significant change of sheet orientation in the late-activated lateral wall. Measured changes in both fiber gradient and sheet structure will affect both the heterogeneity of passive myocardial properties as well as electrical activation of the ventricles.

  View details for PubMedID 16339482

• Orthogonal tensor invariants and the analysis of diffusion tensor magnetic resonance images MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Kindlmann, G. 2006; 55 (1): 136–46

  Abstract

  This paper outlines the mathematical development and application of two analytically orthogonal tensor invariants sets. Diffusion tensors can be mathematically decomposed into shape and orientation information, determined by the eigenvalues and eigenvectors, respectively. The developments herein orthogonally decompose the tensor shape using a set of three orthogonal invariants that characterize the magnitude of isotropy, the magnitude of anisotropy, and the mode of anisotropy. The mode of anisotropy is useful for resolving whether a region of anisotropy is linear anisotropic, orthotropic, or planar anisotropic. Both tensor trace and fractional anisotropy are members of an orthogonal invariant set, but they do not belong to the same set. It is proven that tensor trace and fractional anisotropy are not mutually orthogonal measures of the diffusive process. The results are applied to the analysis and visualization of diffusion tensor magnetic resonance images of the brain in a healthy volunteer. The theoretical developments provide a method for generating scalar maps of the diffusion tensor data, including novel fractional anisotropy maps that are color encoded for the mode of anisotropy and directionally encoded colormaps of only linearly anisotropic structures, rather than of high fractional anisotropy structures.

  View details for PubMedID 16342267

• Visualization of tensor fields using superquadric glyphs MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Kindlman, G., Rodriguez, Helm, P. A., McVeigh, E. R. 2005; 53 (1): 169–76

  Abstract

  The spatially varying tensor fields that arise in magnetic resonance imaging are difficult to visualize due to the multivariate nature of the data. To improve the understanding of myocardial structure and function a family of objects called glyphs, derived from superquadric parametric functions, are used to create informative and intuitive visualizations of the tensor fields. The superquadric glyphs are used to visualize both diffusion and strain tensors obtained in canine myocardium. The eigensystem of each tensor defines the glyph shape and orientation. Superquadric functions provide a continuum of shapes across four distinct eigensystems (lambda(i), sorted eigenvalues), lambda(1) = lambda(2) = lambda(3) (spherical), lambda(1) < lambda(2) = lambda(3) (oblate), lambda(1) > lambda(2) = lambda(3) (prolate), and lambda(1) > lambda(2) > lambda(3) (cuboid). The superquadric glyphs are especially useful for identifying regions of anisotropic structure and function. Diffusion tensor renderings exhibit fiber angle trends and orthotropy (three distinct eigenvalues). Visualization of strain tensors with superquadric glyphs compactly exhibits radial thickening gradients, circumferential and longitudinal shortening, and torsion combined. The orthotropic nature of many biologic tissues and their DTMRI and strain data require visualization strategies that clearly exhibit the anisotropy of the data if it is to be interpreted properly. Superquadric glyphs improve the ability to distinguish fiber orientation and tissue orthotropy compared to ellipsoids.

  View details for DOI 10.1002/mrm.20318

  View details for Web of Science ID 000226380700023

  View details for PubMedID 15690516

  View details for PubMedCentralID PMC2169197

• 3D breath-held cardiac function with projection reconstruction in steady state free precession validated using 2D cine MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Peters, D. C., Ennis, D. B., Rohatgi, P., Syed, M. A., McVeigh, E. R., Arai, A. E. 2004; 20 (3): 411–16

  Abstract

  To develop and validate a three-dimensional (3D) single breath-hold, projection reconstruction (PR), balanced steady state free precession (SSFP) method for cardiac function evaluation against a two-dimensional (2D) multislice Fourier (Cartesian) transform (FT) SSFP method.The 3D PR SSFP sequence used projections in the x-y plane and partitions in z, providing 70-80 msec temporal resolution and 1.7 x 1.7 x 8-10 mm in a 24-heartbeat breath hold. A total of 10 volunteers were imaged with both methods, and the measurements of global cardiac function were compared.Mean signal-to-noise ratios (SNRs) for the blood and myocardium were 114 and 42 (2D) and 59 and 21 (3D). Bland-Altman analysis comparing the 2D and 3D ejection fraction (EF), left ventricular end diastolic volume (LVEDV) and end systolic volume (LVESV), and end diastolic myocardial mass (LVEDM) provided values of bias +/-2 SD of 0.6% +/- 7.7 % for LVEF, 5.9 mL +/- 20 mL for LVEDV, -2.8 mL +/- 12 mL for LVESV, and -0.61 g +/- 13 g for LVEDM. 3D interobserver variability was greater than 2D for LVEDM and LVESV.In a single breath hold, the 3D PR method provides comparable information to the standard 2D FT method, which employs 10-12 breath holds.

  View details for DOI 10.1002/jmri.20145

  View details for Web of Science ID 000223522200009

  View details for PubMedID 15332248

  View details for PubMedCentralID PMC2396304

• Endocardial versus epicardial electrical synchrony during LV free-wall pacing AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Faris, O. P., Evans, F. J., Dick, A. J., Raman, V. K., Ennis, D. B., Kass, D. A., McVeigh, E. R. 2003; 285 (5): H1864–H1870

  Abstract

  Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays (AV delay 0-150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo- and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AVt). AVt was variable among experiments, in the range of 44-93 ms on the epicardium and 47-105 ms on the endocardium. Differences in endo- and epicardial AVt were smaller (-17 to +12 ms) and not significant on average (-5.0 +/- 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well.

  View details for DOI 10.1152/ajpheart.00282.2003

  View details for Web of Science ID 000185951800008

  View details for PubMedID 12855422

  View details for PubMedCentralID PMC2396262

• Assessment of regional systolic and diastolic dysfunction in familial hypertrophic cardiomyopathy using MR tagging MAGNETIC RESONANCE IN MEDICINE Ennis, D. B., Epstein, F. H., Kellman, P., Fananapazir, L., McVeigh, E. R., Arai, A. E. 2003; 50 (3): 638–42

  Abstract

  Diastolic and systolic left ventricular (LV) dysfunction often significantly contribute to disabling symptoms in familial hypertrophic cardiomyopathy (FHC). This study compares regional LV function (midwall circumferential strain) during systole and diastole in eight FHC patients and six normal volunteers (NVs) using MR tagging. A prospectively-gated fast gradient-echo sequence with an echo-train readout was modified to support complementary spatial modulation of magnetization (CSPAMM) tagging and full cardiac cycle data acquisition using the cardiac phase to order reconstruction (CAPTOR), thus providing tag persistence and data acquisition during the entire cardiac cycle. Total systolic strains in FHC patients were significantly reduced in septal and inferior regions (both P < 0.01). Early-diastolic strain rates were reduced in all regions of the FHC group (all P < 0.03). The combination of CSPAMM and CAPTOR allows regional indices of myocardial function to be quantified throughout the cardiac cycle. This technique reveals regional differences in systolic and diastolic impairment in FHC patients.

  View details for PubMedID 12939774

• High-resolution MRI of cardiac function with projection reconstruction and steady-state free precession MAGNETIC RESONANCE IN MEDICINE Peters, D. C., Ennis, D. B., McVeigh, E. R. 2002; 48 (1): 82–88

  Abstract

  The purpose of this study was to investigate the trabecular structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 x 0.8 x 8 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall.

  View details for DOI 10.1002/mrm.10193

  View details for Web of Science ID 000176648900010

  View details for PubMedID 12111934

  View details for PubMedCentralID PMC2396263

• Measurement of F-actin mechanics with laser tracking microrheology: Role of particle surface chemistry. McGrath, J. L., Ennis, D. B., Kuo, S. C. AMER SOC CELL BIOLOGY. 1999: 21A

  View details for Web of Science ID 000083673500122