CAP Profiles

Bio

Bio

My laboratory develops and implements ultrasonic beamforming methods, ultrasonic imaging modalities, and ultrasonic devices. Our current focus is on beamforming methods that are capable of generating high-quality images in the difficult-to-image patient population. These methods include general B-mode and Doppler imaging techniques that utilize additional information from the ultrasonic wavefields. We attempt to build these imaging methods into real-time imaging systems in order to apply them to clinical applications. Other projects in our laboratory include the development of novel ultrasonic imaging devices, such as small, intravascular ultrasound arrays that are capable of generating high acoustic output. These arrays are capable of generating radiation force in order to push on tissue to elucidate the mechanical properties and structure of vascular plaques.

Academic Appointments

Honors & Awards

  • Distinguished Investigator Award, The Academy for Radiology & Biomedical Imaging Research (2018)
  • Outstanding Paper Award, Transactions on Ultrasonics, Ferroelectrics, and Frequency Control (2011)

Boards, Advisory Committees, Professional Organizations

  • Secretary, Basic Science & Instrumentation Community, American Institute of Ultrasound in Medicine (2018 - Present)
  • Associate Editor, IEEE Transactions on Medical Imaging (2017 - Present)
  • Associate Editor, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control (2013 - Present)
  • Associate Editor, Ultrasonic Imaging (2013 - Present)

Professional Education

  • B.S., University of Cincinnati, Electrical Engineering (1999)
  • Ph.D., Duke University, Biomedical Engineering (2004)

Community and International Work

  • Aberration Correction in the Minimum Variance Distortionless Response Beamformer, Lima, Perú

    Topic

    Adaptive Beamforming in Medical Ultrasound

    Partnering Organization(s)

    Pontificia Universidad Católica del Perú

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Patents

  • J. J. Dahl, Y. L. Li. "United States Patent 10,111,644 A Method of Coherent Flow Imaging Using Synthetic Transmit Focusing and Acoustic Reciprocity", Leland Stanford Junior University, Oct 30, 2018
  • J. Doherty, J. J. Dahl, K. R. Nightingale, and G. E. Trahey. "United States Patent 9,883,852 Ultrasound systems, methods and computer program products for estimating tissue deformation with harmonic signals", Duke University, Feb 6, 2018
  • J. J. Dahl, M. A. Lediju Bell, and G. E. Trahey. "United States Patent 9,254,116 Methods, systems and apparatuses for Van-Cittert Zernike imaging", Duke University, Feb 9, 2016

Contact

Links

Research & Scholarship

Current Research and Scholarly Interests

Our laboratory is an ultrasound engineering laboratory that develops and implements ultrasonic beamforming methods, ultrasonic imaging modalities, and ultrasonic devices for diagnostic imaging applications. Our current focus is on beamforming methods that are capable of generating high-quality images in difficult-to-image patients and imaging conditions. These methods include general B-mode and Doppler imaging techniques that utilize additional information from the ultrasonic wavefields to improve image quality. We attempt to build these imaging methods into real-time imaging systems in order to apply them to clinical applications, such as cardiac, liver, and fetal imaging. In addition, our laboratory develops ultrasonic imaging devices, such as small, intravascular ultrasound (IVUS) arrays that are capable of generating high acoustic output. These arrays are capable of generating radiation force in order to push on tissue to elucidate the mechanical properties and structure of vascular plaques, but can be utilized for therapeutic applications of ultrasound as well.

Current projects in our laboratory involve the simulation of nonlinear, acoustic wave propagation under complex models of human anatomy and the impact of anatomy and acoustic parameters on the resulting images. Often, the anatomy and acoustic parameters are the source of aberration and diffuse reverberation of the wavefronts, both of which contribute to image clutter. In addition to modeling and understanding these sources of clutter, we have developed imaging methods that utilize the spatial coherence of the ultrasonic wavefields in order to mitigate the impact of reverberation noise (called short-lag spatial coherence [SLSC], short-lag angular coherence [SLAC], and coherent flow power Doppler [CFPD] imaging) and the estimation of local sound speed in order to mitigate wavefront distortion. These methods demonstrate significant improvement in image quality and the ability to detect slow flow under difficult-to-image scenarios. We have developed a prototype imaging system capable of implementing some of these techniques at up to 30-35 frames per second. We are currently developing methods and approximations to the spatial coherence functions in order to increase the real-time display and image quality. This system will be utilized in clinical studies of cardiac function and placental imaging.

We have recently integrated machine learning techniques to construct neural-network beamformers for a variety of imaging tasks. For example, we recently constructed a neural-network beamformer to output ultrasound images with speckle reduction. These images maintained the resolution of conventional ultrasound images while improving the visualization of tissue structures in human imaging. We have also demonstrated that this neural-network beamformer can be implemented in real-time imaging.

Other projects in our laboratory include development of IVUS and catheter-based arrays to implement radiation-force based imaging techniques (such as Acoustic Radiation Force Impulse [ARFI] imaging and Shear Wave Elastography Imaging [SWEI]), molecular imaging techniques and B7-H3 targeted microbubbles, passive cavitation mapping, and therapeutic ultrasound systems for drug delivery.

Teaching

2019-20 Courses

Stanford Advisees

Publications

All Publications

  • Efficacy of affibody-based ultrasound molecular imaging of vascular B7-H3 for breast cancer detection. Clinical cancer research : an official journal of the American Association for Cancer Research Bam, R., Lown, P. S., Stern, L. A., Sharma, K., Wilson, K. E., Bean, G. R., Lutz, A. M., Paulmurugan, R., Hackel, B. J., Dahl, J., Abou-Elkacem, L. 2020

    Abstract

    Human B7-H3 (hB7-H3) is a promising molecular imaging target differentially expressed on the neovasculature of breast cancer and has been validated for pre-clinical ultrasound (US) imaging with anti-B7-H3-antibody functionalized microbubbles (MB). However, smaller ligands such as affibodies (ABY) are more suitable for the design of clinical-grade targeted-MB.Binding of ABYB7-H3 was confirmed with soluble and cell-surface B7-H3 by flow-cytometry. MB were functionalized with ABYB7-H3 or anti-B7-H3-antibody (AbB7-H3). Control and targeted-MB were tested for binding to hB7-H3-expressing cells (MS1hB7-H3) under shear stress conditions. US imaging was performed with MBABY-B7-H3 in an orthotopic mouse model of human MDA-MB-231 co-implanted with MS1hB7-H3 or control MS1WT cells and a transgenic mouse model of breast cancer development.ABYB7-H3 specifically binds to MS1hB7-H3 and murine-B7-H3-expressing monocytes. MBABY-B7-H3 (8.5 ± 1.4 MB/cell) and MBAb-B7-H3 (9.8 ± 1.3 MB/cell) showed significantly higher (p<0.0001) binding to the MS1hB7-H3 cells compared to control MBNon-targeted (0.5 ± 0.1 MB/cell) under shear stress conditions. In vivo, MBABY-B7-H3 produced significantly higher (p<0.04) imaging signal in orthotopic tumors co-engrafted with MS1hB7-H3 (8.4 ± 3.3 a.u.) compared to tumors with MS1WT cells (1.4 ± 1.0 a.u.). In the transgenic mouse tumors, MBABY-B7-H3 (9.6 ± 2.0 a.u.) produced higher (p<0.0002) imaging signal compared to MBNon-targeted (1.3 ± 0.3 a.u.), while MBABY-B7-H3 signal in normal mammary glands and tumors with B7-H3-blocking significantly reduced (p<0.02) imaging signal.MBABY-B7-H3 enhances B7-H3 molecular signal in breast tumors, improving cancer detection, while offering the advantages of a small size ligand and easier production for clinical imaging.

    View details for DOI 10.1158/1078-0432.CCR-19-1655

    View details for PubMedID 31924738

  • Beamforming and Speckle Reduction Using Neural Networks. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Hyun, D., Brickson, L. L., Looby, K. T., Dahl, J. J. 2019; 66 (5): 898–910

    Abstract

    With traditional beamforming methods, ultrasound B-mode images contain speckle noise caused by the random interference of subresolution scatterers. In this paper, we present a framework for using neural networks to beamform ultrasound channel signals into speckle-reduced B-mode images. We introduce log-domain normalization-independent loss functions that are appropriate for ultrasound imaging. A fully convolutional neural network was trained with the simulated channel signals that were coregistered spatially to ground-truth maps of echogenicity. Networks were designed to accept 16 beamformed subaperture radio frequency (RF) signals. Training performance was compared as a function of training objective, network depth, and network width. The networks were then evaluated on the simulation, phantom, and in vivo data and compared against the existing speckle reduction techniques. The most effective configuration was found to be the deepest (16 layer) and widest (32 filter) networks, trained to minimize a normalization-independent mixture of the l1 and multiscale structural similarity (MS-SSIM) losses. The neural network significantly outperformed delay-and-sum (DAS) and receive-only spatial compounding in speckle reduction while preserving resolution and exhibited improved detail preservation over a nonlocal means method. This work demonstrates that ultrasound B-mode image reconstruction using machine-learned neural networks is feasible and establishes that networks trained solely in silico can be generalized to real-world imaging in vivo to produce images with significantly reduced speckle.

    View details for DOI 10.1109/TUFFC.2019.2903795

    View details for PubMedID 30869612

  • Improved Visualization in Difficult-to-Image Stress Echocardiography Patients Using Real-Time Harmonic Spatial Coherence Imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Hyun, D., Crowley, A. C., LeFevre, M., Cleve, J., Rosenberg, J., Dahl, J. J. 2019; 66 (3): 433–41

    Abstract

    Stress echocardiography is used to detect myocardial ischemia by evaluating cardiovascular function both at rest and at elevated heart rates. Stress echocardiography requires excellent visualization of the left ventricle (LV) throughout the cardiac cycle. However, LV endocardial border visualization is often negatively impacted by high levels of clutter associated with patient obesity, which has risen dramatically worldwide in recent decades. Short-lag spatial coherence (SLSC) imaging has demonstrated reduced clutter in several applications. In this work, a computationally efficient formulation of SLSC was implemented into an object-oriented graphics processing unit-based software beamformer, enabling real-time (>30 frames per second) SLSC echocardiography on a research ultrasound scanner. The system was then used to image 15 difficult-to-image stress echocardiography patients in a comparison study of tissue harmonic imaging (THI) and harmonic spatial coherence imaging (HSCI). Video clips of four standard stress echocardiography views acquired with either THI or HSCI were provided in random shuffled order to three experienced readers. Each reader rated the visibility of 17 LV segments as "invisible," "suboptimally visualized," or "well visualized," with the first two categories indicating a need for contrast agent. In a symmetry test unadjusted for patientwise clustering, HSCI demonstrated a clear superiority over THI ( ). When measured on a per-patient basis, the median total score significantly favored HSCI with . When collapsing the ratings to a two-level scale ("needs contrast" versus "well visualized"), HSCI once again showed an overall superiority over THI, with by McNemar test adjusted for clustering.

    View details for DOI 10.1109/TUFFC.2018.2885777

    View details for Web of Science ID 000461335000003

    View details for PubMedID 30530322

  • Local speed of sound estimation in tissue using pulse-echo ultrasound: Model-based approach. The Journal of the Acoustical Society of America Jakovljevic, M., Hsieh, S., Ali, R., Chau Loo Kung, G., Hyun, D., Dahl, J. J. 2018; 144 (1): 254

    Abstract

    A model and method to accurately estimate the local speed of sound in tissue from pulse-echo ultrasound data is presented. The model relates the local speeds of sound along a wave propagation path to the average speed of sound over the path, and allows one to avoid bias in the sound-speed estimates that can result from overlying layers of subcutaneous fat and muscle tissue. Herein, the average speed of sound using the approach by Anderson and Trahey is measured, and then the authors solve the proposed model for the local sound-speed via gradient descent. The sound-speed estimator was tested in a series of simulation and ex vivo phantom experiments using two-layer media as a simple model of abdominal tissue. The bias of the local sound-speed estimates from the bottom layers is less than 6.2m/s, while the bias of the matched Anderson's estimates is as high as 66m/s. The local speed-of-sound estimates have higher standard deviation than the Anderson's estimates. When the mean local estimate is computed over a 5-by-5mm region of interest, its standard deviation is reduced to less than 7m/s.

    View details for PubMedID 30075660

  • Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma. Journal of controlled release : official journal of the Controlled Release Society Chowdhury, S. M., Lee, T., Bachawal, S. V., Devulapally, R., Abou-Elkacem, L., Yeung, T. A., Wischhusen, J., Tian, L., Dahl, J., Paulmurugan, R., Willmann, J. K. 2018

    Abstract

    Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9-16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed lowering the dose of doxorubicin needed to induce apoptosis. In conclusion, the results of this study suggest that ultrasound-guided and MB-mediated delivery of miRNA-122 and antimiR-21, when combined with doxorubicin, is a highly effective approach to treat resistant HCC while reducing doxorubicin doses needed for treating non-resistant HCC in longitudinal treatment experiments. Further refinement of this strategy could potentially lead to better treatment outcomes for patients with HCC.

    View details for PubMedID 29758233

  • Visualization of Small-Diameter Vessels by Reduction of Incoherent Reverberation With Coherent Flow Power Doppler. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Li, Y. L., Hyun, D., Abou-Elkacem, L., Willmann, J. K., Dahl, J. J. 2016; 63 (11): 1878-1889

    Abstract

    Power Doppler (PD) imaging is a widely used technique for flow detection. Despite the wide use of Doppler ultrasound, limitations exist in the ability of Doppler ultrasound to assess slow flow in the small-diameter vasculature, such as the maternal spiral arteries and fetal villous arteries of the placenta and focal liver lesions. The sensitivity of PD in small vessel detection is limited by the low signal produced by slow flow and the noise associated with small vessels. The noise sources include electronic noise, stationary or slowly moving tissue clutter, reverberation clutter, and off-axis scattering from tissue, among others. In order to provide more sensitive detection of slow flow in small diameter vessels, a coherent flow imaging technique, termed coherent flow PD (CFPD), is characterized and evaluated with simulation, flow phantom experiment studies, and an in vivo animal small vessel detection study. CFPD imaging was introduced as a technique to detect slow blood flow. It has been demonstrated to detect slow flow below the detection threshold of conventional PD imaging using identical pulse sequences and filter parameters. In this paper, we compare CFPD with PD in the detection of blood flow in small-diameter vessels. The results from the study suggest that CFPD is able to provide a 7.5-12.5-dB increase in the signal-to-noise ratio (SNR) over PD images for the same physiological conditions and is less susceptible to reverberation clutter and thermal noise. Due to the increase in SNR, CFPD is able to detect small vessels in high channel noise cases, for which PD was unable to generate enough contrast to observe the vessel.

    View details for PubMedID 27824565

    View details for PubMedCentralID PMC5154731

  • Coherent Flow Power Doppler (CFPD): Flow Detection Using Spatial Coherence Beamforming IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Li, Y. L., Dahl, J. J. 2015; 62 (6): 1022-1035

    Abstract

    Power Doppler imaging is a widely used method of flow detection for tissue perfusion monitoring, inflammatory hyperemia detection, deep vein thrombosis diagnosis, and other clinical applications. However, thermal noise and clutter limit its sensitivity and ability to detect slow flow. In addition, large ensembles are required to obtain sufficient sensitivity, which limits frame rate and yields flash artifacts during moderate tissue motion. We propose an alternative method of flow detection using the spatial coherence of backscattered ultrasound echoes. The method enhances slow flow detection and frame rate, while maintaining or improving the signal quality of conventional power Doppler techniques. The feasibility of this method is demonstrated with simulations, flow-phantom experiments, and an in vivo human thyroid study. In comparison with conventional power Doppler imaging, the proposed method can produce Doppler images with 15- to 30-dB SNR improvement. Therefore, the method is able to detect flow with velocities approximately 50% lower than conventional power Doppler, or improve the frame rate by a factor of 3 with comparable image quality. The results show promise for clinical applications of the method.

    View details for DOI 10.1109/TUFFC.2014.006793

    View details for Web of Science ID 000356162000005

    View details for PubMedID 26067037

    View details for PubMedCentralID PMC4467462

  • Sources of Image Degradation in Fundamental and Harmonic Ultrasound Imaging: A Nonlinear, Full-Wave, Simulation Study (vol 58, pg 754, 2011) IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Pinton, G. F., Trahey, G. E., Dahl, J. J. 2011; 58 (6): 1272-1283

    Abstract

    A full-wave equation that describes nonlinear propagation in a heterogeneous attenuating medium is solved numerically with finite differences in the time domain. This numerical method is used to simulate propagation of a diagnostic ultrasound pulse through a measured representation of the human abdomen with heterogeneities in speed of sound, attenuation, density, and nonlinearity. Conventional delay-and-sum beamforming is used to generate point spread functions (PSFs) that display the effects of these heterogeneities. For the particular imaging configuration that is modeled, these PSFs reveal that the primary source of degradation in fundamental imaging is due to reverberation from near-field structures. Compared with fundamental imaging, reverberation clutter in harmonic imaging is 27.1 dB lower. Simulated tissue with uniform velocity but unchanged impedance characteristics indicates that for harmonic imaging, the primary source of degradation is phase aberration.

    View details for DOI 10.1109/TUFFC.2011.1938

    View details for Web of Science ID 000291880200021

    View details for PubMedID 21693410

  • The role of ultrasound in enhancing mesenchymal stromal cell-based therapies. Stem cells translational medicine Liu, D. D., Ullah, M., Concepcion, W., Dahl, J. J., Thakor, A. S. 2020

    Abstract

    Mesenchymal stromal cells (MSCs) have been a popular platform for cell-based therapy in regenerative medicine due to their propensity to home to damaged tissue and act as a repository of regenerative molecules that can promote tissue repair and exert immunomodulatory effects. Accordingly, a great deal of research has gone into optimizing MSC homing and increasing their secretion of therapeutic molecules. A variety of methods have been used to these ends, but one emerging technique gaining significant interest is the use of ultrasound. Sound waves exert mechanical pressure on cells, activating mechano-transduction pathways and altering gene expression. Ultrasound has been applied both to cultured MSCs to modulate self-renewal and differentiation, and to tissues-of-interest to make them a more attractive target for MSC homing. Here, we review the various applications of ultrasound to MSC-based therapies, including low-intensity pulsed ultrasound, pulsed focused ultrasound, and extracorporeal shockwave therapy, as well as the use of adjunctive therapies such as microbubbles. At a molecular level, it seems that ultrasound transiently generates a local gradient of cytokines, growth factors, and adhesion molecules that facilitate MSC homing. However, the molecular mechanisms underlying these methods are far from fully elucidated and may differ depending on the ultrasound parameters. We thus put forth minimal criteria for ultrasound parameter reporting, in order to ensure reproducibility of studies in the field. A deeper understanding of these mechanisms will enhance our ability to optimize this promising therapy to assist MSC-based approaches in regenerative medicine.

    View details for DOI 10.1002/sctm.19-0391

    View details for PubMedID 32157802

  • Effects of motion on correlations of pulse-echo ultrasound signals: Applications in delay estimation and aperture coherence JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA Hyun, D., Dahl, J. J. 2020; 147 (3): 1323–32

    View details for DOI 10.1121/10.0000809

    View details for Web of Science ID 000519550900001

  • Effects of motion on correlations of pulse-echo ultrasound signals: Applications in delay estimation and aperture coherence. The Journal of the Acoustical Society of America Hyun, D., Dahl, J. J. 2020; 147 (3): 1323

    Abstract

    The correlation between two pulse-echo ultrasound signals is used to achieve a wide range of ultrasound techniques, such as Doppler imaging and elastography. Prior theoretical descriptions of pulse-echo correlations were restricted to stationary scatterers. Here, a theory for the correlation of moving scatterers is presented. An expression is derived for the correlation of two pulse-echo signals with arbitrary transmit and receive apertures acquired from a medium undergoing bulk motion using the Fresnel approximation. The derivation is shown to coincide with prior derivations in the absence of scatterer motion. The theory was compared against simulations in applications of phase-shift estimation and aperture coherence measurements. The phase-shift estimate and jitter were accurately predicted under axial and transverse motion for focused transmit apertures and for sequential and interleaved synthetic transmit apertures. The theory also accurately predicted how motion affects the correlation coefficient between receive aperture elements for a synthetic transmit aperture. The presented theory provides a framework for analyzing the correlations of arbitrary pulse-echo configurations for applications in which scatterer motion is expected.

    View details for DOI 10.1121/10.0000809

    View details for PubMedID 32237854

    View details for PubMedCentralID PMC7051867

  • Improving the Function and Engraftment of Transplanted Pancreatic Islets Using Pulsed Focused Ultrasound Therapy. Scientific reports Razavi, M., Zheng, F., Telichko, A., Wang, J., Ren, G., Dahl, J., Thakor, A. S. 2019; 9 (1): 13416

    Abstract

    This study demonstrates that pulsed focused ultrasound (pFUS) therapy can non-invasively enhance the function and engraftment of pancreatic islets following transplantation. In vitro, we show that islets treated with pFUS at low (peak negative pressure (PNP): 106kPa, spatial peak temporal peak intensity (Isptp): 0.71W/cm2), medium (PNP: 150kPa, Isptp: 1.43W/cm2) or high (PNP: 212kPa, Isptp: 2.86W/cm2) acoustic intensities were stimulated resulting in an increase in their function (i.e. insulin secretion at low-intensity: 1.15±0.17, medium-intensity: 2.02±0.25, and high-intensity: 2.54±0.38 fold increase when compared to control untreated islets; P<0.05). Furthermore, we have shown that this improvement in islet function is a result of pFUS increasing the intracellular concentration of calcium (Ca2+) within islets which was also linked to pFUS increasing the resting membrane potential (Vm) of islets. Following syngeneic renal sub-capsule islet transplantation in C57/B6 mice, pFUS (PNP: 2.9MPa, Isptp: 895W/cm2) improved the function of transplanted islets with diabetic animals rapidly re-establishing glycemic control. In addition, pFUS was able to enhance the engraftment by facilitating islet revascularization and reducing inflammation. Given a significant number of islets are lost immediately following transplantation, pFUS has the potential to be used in humans as a novel non-invasive therapy to facilitate islet function and engraftment, thereby improving the outcome of diabetic patients undergoing islet transplantation.

    View details for DOI 10.1038/s41598-019-49933-0

    View details for PubMedID 31527773

  • Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs. Journal of controlled release : official journal of the Controlled Release Society Di Ianni, T., Bose, R. J., Sukumar, U. K., Bachawal, S., Wang, H., Telichko, A., Herickhoff, C., Robinson, E., Baker, S., Vilches-Moure, J. G., Felt, S. A., Gambhir, S. S., Paulmurugan, R., Dahl, J. D. 2019

    Abstract

    In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.

    View details for DOI 10.1016/j.jconrel.2019.07.024

    View details for PubMedID 31326463

  • Special Issue on Pilot Clinical Translation of New Medical Ultrasound Methodologies IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Gallippi, C. M., Dahl, J. J. 2019; 66 (3): 423–24

    View details for DOI 10.1109/TUFFC.2019.2902085

    View details for Web of Science ID 000461335000001

  • Unsupervised clustering method to convert high-resolution magnetic resonance volumes to three-dimensional acoustic models for full-wave ultrasound simulations. Journal of medical imaging (Bellingham, Wash.) Looby, K., Herickhoff, C. D., Sandino, C., Zhang, T., Vasanawala, S., Dahl, J. J. 2019; 6 (3): 037001

    Abstract

    Simulations of acoustic wave propagation, including both the forward and the backward propagations of the wave (also known as full-wave simulations), are increasingly utilized in ultrasound imaging due to their ability to more accurately model important acoustic phenomena. Realistic anatomic models, particularly those of the abdominal wall, are needed to take full advantage of the capabilities of these simulation tools. We describe a method for converting fat-water-separated magnetic resonance imaging (MRI) volumes to anatomical models for ultrasound simulations. These acoustic models are used to map acoustic imaging parameters, such as speed of sound and density, to grid points in an ultrasound simulation. The tissues of these models are segmented from the MRI volumes into five primary classes of tissue in the human abdominal wall (skin, fat, muscle, connective tissue, and nontissue). This segmentation is achieved using an unsupervised machine learning algorithm, fuzzy c-means clustering (FCM), on a multiscale feature representation of the MRI volumes. We describe an automated method for utilizing FCM weights to produce a model that achieves ∼ 90 % agreement with manual segmentation. Two-dimensional (2-D) and three-dimensional (3-D) full-wave nonlinear ultrasound simulations are conducted, demonstrating the utility of realistic 3-D abdominal wall models over previously available 2-D abdominal wall models.

    View details for DOI 10.1117/1.JMI.6.3.037001

    View details for PubMedID 31338389

    View details for PubMedCentralID PMC6643101

  • Effect of Pulsed Focused Ultrasound on the Native Pancreas. Ultrasound in medicine & biology Razavi, M., Zheng, F., Telichko, A., Ullah, M., Dahl, J., Thakor, A. S. 2019

    Abstract

    Pulsed focused ultrasound (pFUS) utilizes short cycles of sound waves to mechanically shake cells within tissues which, in turn, causes transient local increases in cytokines, growth factors and cell adhesion molecules. Although the effect of pFUS has been investigated in several different organs including the kidney, muscle and heart, its effect on the pancreas has not been investigated. In the present work, we applied pFUS to the rodent pancreas with the following parameters: 1.1-MHz frequency, 5-Hz pulse repetition frequency, 5% duty cycle, 10-ms pulse length, 160-s duration. Low-intensity pFUS had a spatial average temporal average intensity of 11.5 W/cm2 and a negative peak pressure of 3 MPa; high-intensity pFUS had a spatial average temporal average intensity of 18.5 W/cm2 and negative peak pressure of 4 MPa. Here we found that pFUS changed the expression of several cytokines while having no effect on the underlying tissue histology or health of pancreatic cells (as reflected by no significant change in plasma levels of amylase and lipase). Furthermore, we found that this effect on cytokine expression in the pancreas was acoustic intensity dependent; while pFUS at low intensities turned off the expression of several cytokines, at high intensities it had the opposite effect and turned on the expression of these cytokines. The ability to non-invasively manipulate the microenvironment of the pancreas using sound waves could have profound implications for priming and modulating this organ for the application of cellular therapies in the context of both regenerative medicine (i.e., diabetes and pancreatitis) and oncology (i.e., pancreatic cancer).

    View details for DOI 10.1016/j.ultrasmedbio.2019.11.016

    View details for PubMedID 31882169

  • A Locally Adaptive Phase Aberration Correction (LAPAC) Method for Synthetic Aperture Sequences ULTRASONIC IMAGING Chau, G., Jakovljevic, M., Lavarello, R., Dahl, J. 2019; 41 (1): 3–16

    View details for DOI 10.1177/0161734618796556

    View details for Web of Science ID 000453084900001

  • Vector Flow Velocity Estimation from Beamsummed Data Using Deep Neural Networks Li, Y., Hyun, D., Dahl, J. J., IEEE IEEE. 2019: 860–63

    View details for Web of Science ID 000510220100220

  • Travel-Time Tomography for Local Sound Speed Reconstruction Using Average Sound Speeds Ali, R., Dahl, J. J., IEEE IEEE. 2019: 2007–10

    View details for Web of Science ID 000510220100515

  • An Open Source GPU-Based Beamformer for Real-Time Ultrasound Imaging and Applications Hyun, D., Li, Y., Steinberg, I., Jakovljevic, M., Klap, T., Dahl, J. J., IEEE IEEE. 2019: 20–23

    View details for Web of Science ID 000510220100006

  • Iterative Retrospective Recovery of Full Synthetic Aperture Data from Focused Transmissions Ali, R., Dahl, J. J., Bottenus, N., IEEE IEEE. 2019: 1005–8

    View details for Web of Science ID 000510220100256

  • Low-cost Sensor-enabled Freehand 3D Ultrasound Herickhoff, C., Lin, J., Dahl, J., IEEE IEEE. 2019: 498–501

    View details for Web of Science ID 000510220100128

  • Axially-segmented cylindrical array for intravascular shear wave imaging Telichko, A., Herickhoff, C. D., Dahl, J. J., Byram, B. C., Ruiter, N. V. SPIE-INT SOC OPTICAL ENGINEERING. 2019

    View details for DOI 10.1117/12.2512582

    View details for Web of Science ID 000471826100012

  • Estimating Signal and Structured Noise in Ultrasound Data using Prediction-Error Filters Jennings, J., Jakovljevic, M., Biondi, E., Dahl, J., Biondi, B., Byram, B. C., Ruiter, N. V. SPIE-INT SOC OPTICAL ENGINEERING. 2019

    View details for DOI 10.1117/12.2513514

    View details for Web of Science ID 000471826100024

  • Open-Source Gauss-Newton-Based Methods for Refraction-Corrected Ultrasound Computed Tomography Ali, R., Hsieh, S., Dahl, J., Byram, B. C., Ruiter, N. V. SPIE-INT SOC OPTICAL ENGINEERING. 2019

    View details for DOI 10.1117/12.2511319

    View details for Web of Science ID 000471826100006

  • Tracking Blood Flow Changes in the Brains of Neonates using Angular-coherence-based Power Doppler Jakovljevic, M., Yoon, B., Abou-Elkacem, L., Rubesova, E., Dahl, J., Byram, B. C., Ruiter, N. V. SPIE-INT SOC OPTICAL ENGINEERING. 2019

    View details for DOI 10.1117/12.2513554

    View details for Web of Science ID 000471826100014

  • Versatile Low-Cost Volumetric 3-D Ultrasound Platform for Existing Clinical 2-D Systems IEEE TRANSACTIONS ON MEDICAL IMAGING Morgan, M. R., Broder, J. S., Dahl, J. J., Herickhoff, C. D. 2018; 37 (10): 2248–56

    Abstract

    Ultrasound imaging has indications across many areas of medicine, but the need for training and the variability in skill and acquired image quality among 2-D ultrasound users have limited its wider adoption and utilization. Low-cost volumetric ultrasound with a known frame of reference has the potential to lower these operator-dependent barriers and enhance the clinical utility of ultrasound imaging. In this paper, we improve upon our previous research-scanner-based prototype to implement a versatile volumetric imaging platform for existing clinical 2-D ultrasound systems. We present improved data acquisition and image reconstruction schemes to increase quality, streamline workflow, and provide real-time visual feedback. We present initial results using the platform on a Vimedix simulator, as well as on phantom and in vivo targets using a variety of clinical ultrasound systems and probes.

    View details for DOI 10.1109/TMI.2018.2821901

    View details for Web of Science ID 000446342100008

    View details for PubMedID 29993653

  • Measurements of the Relationship Between CT Hounsfield Units and Acoustic Velocity and How It Changes With Photon Energy and Reconstruction Method IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Webb, T. D., Leung, S. A., Rosenberg, J., Ghanouni, P., Dahl, J. J., Pelc, N. J., Pauly, K. 2018; 65 (7): 1111–24

    Abstract

    Transcranial magnetic resonance-guided focused ultrasound continues to gain traction as a noninvasive treatment option for a variety of pathologies. Focusing ultrasound through the skull can be accomplished by adding a phase correction to each element of a hemispherical transducer array. The phase corrections are determined with acoustic simulations that rely on speed of sound estimates derived from CT scans. While several studies have investigated the relationship between acoustic velocity and CT Hounsfield units (HUs), these studies have largely ignored the impact of X-ray energy, reconstruction method, and reconstruction kernel on the measured HU, and therefore the estimated velocity, and none have measured the relationship directly. In this paper, 91 ex vivo human skull fragments from two skulls are imaged by 80 CT scans with a variety of energies and reconstruction methods. The average HU from each fragment is found for each scan and correlated with the speed of sound measured using a through transmission technique in that fragment. As measured by the -squared value, the results show that CT is able to account for 23%-53% of the variation in velocity in the human skull. Both the X-ray energy and the reconstruction technique significantly alter the -squared value and the linear relationship between HU and speed of sound in bone. Accounting for these variations will lead to more accurate phase corrections and more efficient transmission of acoustic energy through the skull.

    View details for DOI 10.1109/TUFFC.2018.2827899

    View details for Web of Science ID 000436933000004

    View details for PubMedID 29993366

  • Improved Sensitivity in Ultrasound Molecular Imaging With Coherence-Based Beamforming. IEEE transactions on medical imaging Hyun, D., Abou-Elkacem, L., Perez, V. A., Chowdhury, S. M., Willmann, J. K., Dahl, J. J. 2018; 37 (1): 241–50

    Abstract

    Ultrasound molecular imaging (USMI) is accomplished by detecting microbubble (MB) contrast agents that have bound to specific biomarkers, and can be used for a variety of imaging applications, such as the early detection of cancer. USMI has been widely utilized in preclinical imaging in mice; however, USMI in humans can be challenging because of the low concentration of bound MBs and the signal degradation caused by the presence of heterogenous soft tissue between the transducer and the lesion. Short-lag spatial coherence (SLSC) beamforming has been proposed as a robust technique that is less affected by poor signal quality than standard delay-and-sum (DAS) beamforming. In this paper, USMI performance was assessed using contrast-enhanced ultrasound imaging combined with DAS (conventional CEUS) and with SLSC (SLSC-CEUS). Each method was characterized by flow channel phantom experiments. In a USMI-mimicking phantom, SLSC-CEUS was found to be more robust to high levels of additive thermal noise than DAS, with a 6dB SNR improvement when the thermal noise level was +6dB or higher. However, SLSC-CEUS was also found to be insensitive to increases in MB concentration, making it a poor choice for perfusion imaging. USMI performance was also measured in vivo using VEGFR2-targeted MBs in mice with subcutaneous human hepatocellular carcinoma tumors, with clinical imaging conditions mimicked using a porcine tissue layer between the tumor and the transducer. SLSC-CEUS improved the SNR in each of ten tumors by an average of 41%, corresponding to 3.0dB SNR. These results indicate that the SLSC beamformer is well-suited for USMI applications because of its high sensitivity and robust properties under challenging imaging conditions.

    View details for DOI 10.1109/TMI.2017.2774814

    View details for PubMedID 29293430

    View details for PubMedCentralID PMC5764183

  • Reverberation Noise Suppression in the Aperture Domain Using 3D Fully Convolutional Neural Networks Brickson, L. L., Hyun, D., Dahl, J. J., IEEE IEEE. 2018

    View details for Web of Science ID 000458693001046

  • Distributed Phase Aberration Correction Techniques Based on Local Sound Speed Estimates Ali, R., Dahl, J. J., IEEE IEEE. 2018

    View details for Web of Science ID 000458693001161

  • Regularized Inversion Method for Frequency-Domain Recovery of the Full Synthetic Aperture Dataset From Focused Transmissions Ali, R., Dahl, J. J., Bottenus, N., IEEE IEEE. 2018

    View details for Web of Science ID 000458693001220

  • High Sensitivity Liver Vasculature Visualization Using a Real-time Coherent Flow Power Doppler (CFPD) Imaging System: A Pilot Clinical Study Li, Y., Hyun, D., Durot, I., Willmann, J. K., Dahl, J. J., IEEE IEEE. 2018

    View details for Web of Science ID 000458693000074

  • Adaptive Grayscale Mapping to Improve Molecular Ultrasound Difference Images Shu, J., Hyun, D., Abou-Elkacem, L., Willmann, J., Dahl, J., IEEE IEEE. 2018

    View details for Web of Science ID 000458693001138

  • Effects of Phase Aberration and Phase Aberration Correction on the Minimum Variance Beamformer. Ultrasonic imaging Chau, G., Dahl, J., Lavarello, R. 2018; 40 (1): 15–34

    Abstract

    The minimum variance (MV) beamformer has the potential to enhance the resolution and contrast of ultrasound images but is sensitive to steering vector errors. Robust MV beamformers have been proposed but mainly evaluated in the presence of gross sound speed mismatches, and the impact of phase aberration correction (PAC) methods in mitigating the effects of phase aberration in MV beamformed images has not been explored. In this study, an analysis of the effects of aberration on conventional MV and eigenspace MV (ESMV) beamformers is carried out. In addition, the impact of three PAC algorithms on the performance of MV beamforming is analyzed. The different beamformers were tested on simulated data and on experimental data corrupted with electronic and tissue-based aberration. It is shown that all gains in performance of the MV beamformer with respect to delay-and-sum (DAS) are lost at high aberration strengths. For instance, with an electronic aberration of 60 ns, the lateral resolution of DAS degrades by 17% while MV degrades by 73% with respect to the images with no aberration. Moreover, although ESMV shows robustness at low aberration levels, its degradation at higher aberrations is approximately the same as that of regular MV. It is also shown that basic PAC methods improve the aberrated MV beamformer. For example, in the case of electronic aberration, multi-lag reduces degradation in lateral resolution from 73% to 28% and contrast loss from 85% to 25%. These enhancements allow the combination of MV and PAC to outperform DAS and PAC and ESMV in moderate and strong aberrations. We conclude that the effect of aberration on the MV beamformer is stronger than previously reported in the literature and that PAC is needed to improve its clinical potential.

    View details for PubMedID 28703644

  • B-line detection using amplitude modulation-frequency modulation (AM-FM) features SPIE MEDICAL IMAGING Chau, G., Mamani, G., Fortunić, E., Serpa, S., Zenteno, O., Ramos, D., Peña, G., Fredes, G., Chura, E., Ticona, E., Manella, H., Lobo, V., Dahl, J., Castañeda, B., Lavarello, R. 2018; 10580

    View details for DOI 10.1117/12.2285224

  • K-Means Clustering for High-Resolution, Realistic Acoustic Maps Looby, K., Sandino, C., Zhang, T., Vasanawala, S., Dahl, J., Duric, N., Byram, B. C. SPIE-INT SOC OPTICAL ENGINEERING. 2018

    View details for DOI 10.1117/12.2293990

    View details for Web of Science ID 000450861900027

  • Effects of Phase Aberration and Phase Aberration Correction on the Minimum Variance Beamformer ULTRASONIC IMAGING Chau, G., Dahl, J., Lavarello, R. 2018; 40 (1): 15–34

    View details for DOI 10.1177/0161734617717768

    View details for Web of Science ID 000416381400002

  • Low-cost Volumetric Ultrasound by Augmentation of 2D Systems: Design and Prototype. Ultrasonic imaging Herickhoff, C. D., Morgan, M. R., Broder, J. S., Dahl, J. J. 2017: 161734617718528

    Abstract

    Conventional two-dimensional (2D) ultrasound imaging is a powerful diagnostic tool in the hands of an experienced user, yet 2D ultrasound remains clinically underutilized and inherently incomplete, with output being very operator dependent. Volumetric ultrasound systems can more fully capture a three-dimensional (3D) region of interest, but current 3D systems require specialized transducers, are prohibitively expensive for many clinical departments, and do not register image orientation with respect to the patient; these systems are designed to provide improved workflow rather than operator independence. This work investigates whether it is possible to add volumetric 3D imaging capability to existing 2D ultrasound systems at minimal cost, providing a practical means of reducing operator dependence in ultrasound. In this paper, we present a low-cost method to make 2D ultrasound systems capable of quality volumetric image acquisition: we present the general system design and image acquisition method, including the use of a probe-mounted orientation sensor, a simple probe fixture prototype, and an offline volume reconstruction technique. We demonstrate initial results of the method, implemented using a Verasonics Vantage research scanner.

    View details for PubMedID 28691586

  • Angular coherence in ultrasound imaging: Theory and applications JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA Li, Y. L., Dahl, J. J. 2017; 141 (3): 1582-1594

    Abstract

    The popularity of plane-wave transmits at multiple transmit angles for synthetic transmit aperture (or coherent compounding) has spawned a number of adaptations and new developments of ultrasonic imaging. However, the coherence properties of backscattered signals with plane-wave transmits at different angles are unknown and may impact a subset of these techniques. To provide a framework for the analysis of the coherence properties of such signals, this article introduces the angular coherence theory in medical ultrasound imaging. The theory indicates that the correlation function of such signals forms a Fourier transform pair with autocorrelation function of the receive aperture function. This conclusion can be considered as an extended form of the van Cittert Zernike theorem. The theory is validated with simulation and experimental results obtained on speckle targets. On the basis of the angular coherence of the backscattered wave, a new short-lag angular coherence beamformer is proposed and compared with an existing spatial-coherence-based beamformer. An application of the theory in phase shift estimation and speed of sound estimation is also presented.

    View details for DOI 10.1121/1.4976960

    View details for Web of Science ID 000398962500043

    View details for PubMedID 28372139

  • Efficient Strategies for Estimating the Spatial Coherence of Backscatter IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Hyun, D., Crowley, A. L., Dahl, J. J. 2017; 64 (3): 500-513

    Abstract

    The spatial coherence of ultrasound backscatter has been proposed to reduce clutter in medical imaging, to measure the anisotropy of the scattering source, and to improve the detection of blood flow. These techniques rely on correlation estimates that are obtained using computationally expensive strategies. In this paper, we assess the existing spatial coherence estimation methods and propose three computationally efficient modifications: a reduced kernel, a downsampled receive aperture, and the use of an ensemble correlation coefficient. The proposed methods are implemented in simulation and in vivo studies. Reducing the kernel to a single sample improved computational throughput and improved axial resolution. Downsampling the receive aperture was found to have negligible effect on estimator variance, and improved computational throughput by an order of magnitude for a downsample factor of 4. The ensemble correlation estimator demonstrated lower variance than the currently used average correlation. Combining the three methods, the throughput was improved 105-fold in simulation with a downsample factor of 4- and 20-fold in vivo with a downsample factor of 2.

    View details for DOI 10.1109/TUFFC.2016.2634004

    View details for Web of Science ID 000396399400002

    View details for PubMedCentralID PMC5453518

  • Coherence Beamforming and its Applications to the Difficult-to-Image Patient Dahl, J. J., Hyun, D., Li, Y., Jakovljevic, M., Bell, M. L., Long, W. J., Bottenus, N., Kakkad, V., Trahey, G. E., IEEE IEEE. 2017

    View details for Web of Science ID 000416948400035

  • Advances in Ultrasonic Imaging Technology Advances in Medical Physics – 2016 Herickhoff, C. D., Dahl, J. J. Medical Physics Publishing. 2016: 71–96
  • Effects of Phase Aberration Correction Methods on the Minimum Variance Beamformer 2016 IEEE 38th Annual International Conference of the Engineering in Medicine and Biology Society (EMBC) Chau, G. R., Dahl, J. J., Lavarello, R. J. 2016: 3231–34

    View details for DOI 10.1109/EMBC.2016.7591417

  • Comparison of Acoustic Radiation Force Impulse Imaging Derived Carotid Plaque Stiffness With Spatially Registered MRI Determined Composition IEEE TRANSACTIONS ON MEDICAL IMAGING Doherty, J. R., Dahl, J. J., Kranz, P. G., El Husseini, N., Chang, H., Chen, N., Allen, J. D., Ham, K. L., Trahey, G. E. 2015; 34 (11): 2354-2365

    Abstract

    Measurements of plaque stiffness may provide important prognostic and diagnostic information to help clinicians distinguish vulnerable plaques containing soft lipid pools from more stable, stiffer plaques. In this preliminary study, we compare in vivo ultrasonic Acoustic Radiation Force Impulse (ARFI) imaging derived measures of carotid plaque stiffness with composition determined by spatially registered Magnetic Resonance Imaging (MRI) in five human subjects with stenosis > 50%. Ultrasound imaging was implemented on a commercial diagnostic scanner with custom pulse sequences to collect spatially registered 2D longitudinal B-mode and ARFI images. A standardized, multi-contrast weighted MRI sequence was used to obtain 3D Time of Flight (TOF), T1 weighted (T1W), T2 weighted (T2W), and Proton Density Weighted (PDW) transverse image stacks of volumetric data. The MRI data was segmented to identify lipid, calcium, and normal loose matrix components using commercially available software. 3D MRI segmented plaque models were rendered and spatially registered with 2D B-mode images to create fused ultrasound and MRI volumetric images for each subject. ARFI imaging displacements in regions of interest (ROIs) derived from MRI segmented contours of varying composition were compared. Regions of calcium and normal loose matrix components identified by MRI presented as homogeneously stiff regions of similarly low (typically ≈ 1 μm) displacement in ARFI imaging. MRI identified lipid pools > 2 mm(2), found in three out of five subjects, presented as softer regions of increased displacement that were on average 1.8 times greater than the displacements in adjacent regions of loose matrix components in spatially registered ARFI images. This work provides early evidence supporting the use of ARFI imaging to noninvasively identify lipid regions in carotid artery plaques in vivo that are believed to increase the propensity of a plaque to rupture. Additionally, the results provide early training data for future studies and aid in the interpretation and possible clinical utility of ARFI imaging for identifying the elusive vulnerable plaque.

    View details for DOI 10.1109/TMI.2015.2432797

    View details for Web of Science ID 000364461000013

    View details for PubMedID 25974933

    View details for PubMedCentralID PMC4678151

  • Resolution and Brightness Characteristics of Short-Lag Spatial Coherence (SLSC) Images IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Bell, M. A., Dahl, J. J., Trahey, G. E. 2015; 62 (7): 1265-1276

    Abstract

    We previously described a novel beamforming method that images the spatial correlation of an echo wave field with demonstrated applications to clutter reduction in high-noise environments. In this paper, several characteristics of the resolution and brightness of short-lag spatial coherence (SLSC) images formed by this method are compared with B-mode images formed by conventional delay-and-sum beamforming methods. Point target widths were measured to estimate resolution, the autocorrelation of image texture was measured to estimate texture size, and the contrast (i.e., brightness ratio) of clinically relevant targets was assessed. SLSC images demonstrate improved resolution and contrast with increasing values of channel noise and clutter, whereas B-mode resolution was degraded in the presence of high noise (i.e., > -12 dB channel noise-to-signal ratios) and high clutter magnitudes (i.e., > -21 dB relative to point target magnitude). Lateral resolution in SLSC images was improved with increasing lag value, whereas axial resolution was degraded with increasing correlation kernel length. The texture size of SLSC images was smaller than that of matched B-mode images. Results demonstrate that the resolution and contrast of coherence-based images depend on a range of parameters, but are generally superior to those of matched B-mode images under challenging imaging conditions.

    View details for DOI 10.1109/TUFFC.2014.006909

    View details for Web of Science ID 000357960000004

    View details for PubMedID 26168173

  • In Vivo Application of Short-Lag Spatial Coherence and Harmonic Spatial Coherence Imaging in Fetal Ultrasound ULTRASONIC IMAGING Kakkad, V., Dahl, J., Ellestad, S., Trahey, G. 2015; 37 (2): 101-116

    Abstract

    Fetal scanning is one of the most common applications of ultrasound imaging and serves as a source of vital information about maternal and fetal health. Visualization of clinically relevant structures, however, can be severely compromised in difficult-to-image patients due to poor resolution and the presence of high levels of acoustical noise or clutter. We have developed novel coherence-based beamforming methods called Short-Lag Spatial Coherence (SLSC) imaging and Harmonic Spatial Coherence imaging (HSCI), and applied them to suppress the effects of clutter in fetal imaging. This method is used to create images of the spatial coherence of the backscattered ultrasound as opposed to images of echo magnitude. We present the results of a patient study to assess the benefits of coherence-based beamforming in the context of first trimester fetal exams. Matched fundamental B-mode, SLSC, harmonic B-mode, and HSCI images were generated using raw radio frequency data collected on 11 volunteers in the first trimester of pregnancy. The images were compared for qualitative differences in image texture and target conspicuity as well as using quantitative imaging metrics such as signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast. SLSC and HSCI showed statistically significant improvements across all imaging metrics compared with B-mode and harmonic B-mode, respectively. These improvements were greatest for poor quality B-mode images where contrast of anechoic targets was improved from 15 dB in fundamental B-mode to 27 dB in SLSC and 17 dB in harmonic B-mode to 30 dB in HSCI. CNR improved from 1.4 to 2.5 in the fundamental images and 1.4 to 3.1 in the harmonic case. These results exhibit the potential of coherence-based beamforming to improve image quality and target detectability, especially in high noise environments.

    View details for DOI 10.1177/0161734614547281

    View details for Web of Science ID 000350487500002

    View details for PubMedID 25116292

  • Intravascular acoustic radiation force imaging: Feasibility study IEEE International Ultrasonics Symposium (IUS) Herickhoff, C. D., Dahl, J. J. 2015

    View details for DOI 10.1109/ULTSYM.2015.0118

  • Coherence Beamforming Applied to Velocity Estimation and Partially Coherent Signals IEEE International Ultrasonics Symposium (IUS) Dahl, J. J., You, L., Hyun, D., Doherty, J. R. 2015

    View details for DOI 10.1109/ULTSYM.2015.0013

  • Small-diameter Vasculature Detection with Coherent Flow Power Doppler Imaging IEEE International Ultrasonics Symposium (IUS) You, L., Dahl, J. J. 2015

    View details for DOI 10.1109/ULTSYM.2015.0012

  • Real-Time High-Framerate In Vivo Cardiac SLSC Imaging with a GPU-Based Beamformer IEEE International Ultrasonics Symposium (IUS) Hyun, D., Trahey, G. E., Dahl, J. J. 2015

    View details for DOI 10.1109/ULTSYM.2015.0077

  • Spatial Coherence in Human Tissue: Implications for Imaging and Measurement IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Pinton, G. F., Trahey, G. E., Dahl, J. J. 2014; 61 (12): 1976-1987

    Abstract

    The spatial coherence properties of the signal backscattered by human tissue and measured by an ultrasound transducer array are investigated. Fourier acoustics are used to describe the propagation of ultrasound through a model of tissue that includes reverberation and random scattering in the imaging plane. The theoretical development describes how the near-field tissue layer, transducer aperture properties, and reflectivity function at the focus reduce the spatial coherence of the imaging wave measured at the transducer surface. Simulations are used to propagate the acoustic field through a histologically characterized sample of the human abdomen and to validate the theoretical predictions. In vivo measurements performed with a diagnostic ultrasound scanner demonstrate that simulations and theory closely match the measured spatial coherence characteristics in the human body across the transducer array's entire spatial extent. The theoretical framework and simulations are then used to describe the physics of spatial coherence imaging, a type of ultrasound imaging that measures coherence properties instead of echo brightness. The same echo data from an F/2 transducer was used to generate B-mode and short lag spatial coherence images. For an anechoic lesion at the focus, the contrast-to-noise ratio is 1.21 for conventional B-mode imaging and 1.95 for spatial coherence imaging. It is shown that the contrast in spatial coherence imaging depends on the properties of the near-field tissue layer and the backscattering function in the focal plane.

    View details for DOI 10.1109/TUFFC.2014.006362

    View details for Web of Science ID 000345944300006

    View details for PubMedID 25474774

    View details for PubMedCentralID PMC4261956

  • Short-Lag Spatial Coherence Imaging on Matrix Arrays, Part II: Phantom and In Vivo Experiments IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Jakovljevic, M., Byram, B. C., Hyun, D., Dahl, J. J., Trahey, G. E. 2014; 61 (7): 1113-1122

    Abstract

    In Part I of the paper, we demonstrated through simulation the potential of volumetric short-lag spatial coherence (SLSC) imaging to improve visualization of hypoechoic targets in three dimensions. Here, we demonstrate the application of volumetric SLSC imaging in phantom and in vivo experiments using a clinical 3-D ultrasound scanner and matrix array. Using a custom single-channel acquisition tool, we collected partially beamformed channel data from the fully sampled matrix array at high speeds and created matched Bmode and SLSC volumes of a vessel phantom and in vivo liver vasculature. 2-D and 3-D images rendered from the SLSC volumes display reduced clutter and improved visibility of the vessels when compared with their B-mode counterparts. We use concurrently acquired color Doppler volumes to confirm the presence of the vessels of interest and to define the regions inside the vessels used in contrast and contrast-to-noise ratio (CNR) calculations. SLSC volumes show higher CNR values than their matched B-mode volumes, while the contrast values appear to be similar between the two imaging methods.

    View details for DOI 10.1109/TUFFC.2014.3011

    View details for Web of Science ID 000338665500005

    View details for PubMedID 24960701

    View details for PubMedCentralID PMC4234201

  • Short-Lag Spatial Coherence Imaging on Matrix Arrays, Part I: Beamforming Methods and Simulation Studies IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Hyun, D., Trahey, G. E., Jakovljevic, M., Dahl, J. J. 2014; 61 (7): 1101-1112

    Abstract

    Short-lag spatial coherence (SLSC) imaging is a beamforming technique that has demonstrated improved imaging performance compared with conventional B-mode imaging in previous studies. Thus far, the use of 1-D arrays has limited coherence measurements and SLSC imaging to a single dimension. Here, the SLSC algorithm is extended for use on 2-D matrix array transducers and applied in a simulation study examining imaging performance as a function of subaperture configuration and of incoherent channel noise. SLSC images generated with a 2-D array yielded superior contrast-to-noise ratio (CNR) and texture SNR measurements over SLSC images made on a corresponding 1-D array and over B-mode imaging. SLSC images generated with square subapertures were found to be superior to SLSC images generated with subapertures of equal surface area that spanned the whole array in one dimension. Subaperture beamforming was found to have little effect on SLSC imaging performance for subapertures up to 8 x 8 elements in size on a 64 × 64 element transducer. Additionally, the use of 8 x 8, 4 x 4, and 2 x 2 element subapertures provided 8, 4, and 2 times improvement in channel SNR along with 2640-, 328-, and 25-fold reduction in computation time, respectively. These results indicate that volumetric SLSC imaging is readily applicable to existing 2-D arrays that employ subaperture beamforming.

    View details for DOI 10.1109/TUFFC.2014.3010

    View details for Web of Science ID 000338665500004

    View details for PubMedID 24960700

    View details for PubMedCentralID PMC4235772

  • Estimation of shear wave speed in the human uterine cervix ULTRASOUND IN OBSTETRICS & GYNECOLOGY Carlson, L. C., Feltovich, H., Palmeri, M. L., Dahl, J. J., Munoz Del Rio, A., Hall, T. J. 2014; 43 (4): 452-458

    Abstract

    To explore spatial variability within the cervix and the sensitivity of shear wave speed (SWS) to assess softness/stiffness differences in ripened (softened) vs unripened tissue.We obtained SWS estimates from hysterectomy specimens (n = 22), a subset of which were ripened (n = 13). Multiple measurements were made longitudinally along the cervical canal on both the anterior and posterior sides of the cervix. Statistical tests of differences in the proximal vs distal, anterior vs posterior and ripened vs unripened cervix were performed with individual two-sample t-tests and a linear mixed model.Estimates of SWS increase monotonically from distal to proximal longitudinally along the cervix, they vary in the anterior compared to the posterior cervix and they are significantly different in ripened vs unripened cervical tissue. Specifically, the mid position SWS estimates for the unripened group were 3.45 ± 0.95 m/s (anterior; mean ± SD) and 3.56 ± 0.92 m/s (posterior), and 2.11 ± 0.45 m/s (anterior) and 2.68 ± 0.57 m/s (posterior) for the ripened group (P < 0.001).We propose that SWS estimation may be a valuable research and, ultimately, diagnostic tool for objective quantification of cervical stiffness/softness.

    View details for DOI 10.1002/uog.12555

    View details for Web of Science ID 000333696800013

    View details for PubMedID 23836486

  • Acoustic Radiation Force Impulse Imaging (ARFI) on an IVUS Circular Array ULTRASONIC IMAGING Patel, V., Dahl, J. J., Bradway, D. P., Doherty, J. R., Lee, S. Y., Smith, S. W. 2014; 36 (2): 98-111

    Abstract

    Our long-term goal is the detection and characterization of vulnerable plaque in the coronary arteries of the heart using intravascular ultrasound (IVUS) catheters. Vulnerable plaque, characterized by a thin fibrous cap and a soft, lipid-rich necrotic core is a precursor to heart attack and stroke. Early detection of such plaques may potentially alter the course of treatment of the patient to prevent ischemic events. We have previously described the characterization of carotid plaques using external linear arrays operating at 9 MHz. In addition, we previously modified circular array IVUS catheters by short-circuiting several neighboring elements to produce fixed beamwidths for intravascular hyperthermia applications. In this paper, we modified Volcano Visions 8.2 French, 9 MHz catheters and Volcano Platinum 3.5 French, 20 MHz catheters by short-circuiting portions of the array for acoustic radiation force impulse imaging (ARFI) applications. The catheters had an effective transmit aperture size of 2 mm and 1.5 mm, respectively. The catheters were connected to a Verasonics scanner and driven with pushing pulses of 180 V p-p to acquire ARFI data from a soft gel phantom with a Young's modulus of 2.9 kPa. The dynamic response of the tissue-mimicking material demonstrates a typical ARFI motion of 1 to 2 microns as the gel phantom displaces away and recovers back to its normal position. The hardware modifications applied to our IVUS catheters mimic potential beamforming modifications that could be implemented on IVUS scanners. Our results demonstrate that the generation of radiation force from IVUS catheters and the development of intravascular ARFI may be feasible.

    View details for DOI 10.1177/0161734613511595

    View details for Web of Science ID 000331541600002

    View details for PubMedID 24554291

    View details for PubMedCentralID PMC4176895

  • REVERBERATION CLUTTER FROM SUBCUTANEOUS TISSUE LAYERS: SIMULATION AND IN VIVO DEMONSTRATIONS ULTRASOUND IN MEDICINE AND BIOLOGY Dahl, J. J., Sheth, N. M. 2014; 40 (4): 714-726

    Abstract

    The degradation of ultrasonic image quality is typically attributed to aberration and reverberation. Although the sources and impact of aberration are well understood, very little is known about the source and impact of image degradation caused by reverberation. Reverberation is typically associated with multiple reflections at two interfaces along the same propagation path, as with the arterial wall or a metal sphere. However, the reverberation that results in image degradation includes more complex interaction between the propagating wave and the tissue. Simulations of wave propagation in realistic and simplified models of the abdominal wall are used to illustrate the characteristics of coherent and diffuse clutter generated by reverberation. In the realistic models, diffuse reverberation clutter is divided into that originating from the tissue interfaces and that originating from sub-resolution diffuse scatterers. In the simplified models, the magnitude of the reverberation clutter is observed as angle and density of the connective tissue are altered. The results suggest that multi-path scattering from the connective tissue/fat interfaces is a dominant component of reverberation clutter. Diffuse reverberation clutter is maximal when the connective tissue is near normal to the beam direction and increases with the density of connective tissue layers at these large angles. The presence of a thick fascial or fibrous layer at the distal boundary of the abdominal wall magnifies the amount of reverberation clutter. The simulations also illustrate that compression of the abdominal layer, a technique often used to mitigate clutter in overweight and obese patients, increases the decay of reverberation clutter with depth. In addition, rotation of the transducer or steering of the beam with respect to highly reflecting boundaries can reduce coherent clutter and transform it to diffuse clutter, which can be further reduced using coherence-based beamforming techniques. In vivo images of the human bladder illustrate some of the reverberation effects observed in simulation.

    View details for DOI 10.1016/j.ultrasmedbio.2013.11.029

    View details for Web of Science ID 000332027300007

    View details for PubMedID 24530261

    View details for PubMedCentralID PMC3942094

  • Accuracy of backscatter coefficient estimation in aberrating media using different phase aberration correction strategies – a simulation study IEEE International Ultrasonics Symposium (IUS) Gonzalez, E., Sheth, N., Castaneda, B., Dahl, J. J., Lavarello, R. 2014: 2438–41
  • Flow detection based on the spatial coherence of backscattered echoes IEEE International Ultrasonics Symposium (IUS) Li, Y., Dahl, J. J. 2014: 428–31
  • Sparse sampling methods for efficient spatial coherence estimation IEEE International Ultrasonics Symposium (IUS) Hyun, D., Trahey, G. E., Dahl, J. J. 2014: 535–38
  • Harmonic Tracking of Acoustic Radiation Force-Induced Displacements IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Doherty, J. R., Dahl, J. J., Trahey, G. E. 2013; 60 (11): 2347-2358

    Abstract

    Ultrasound-based elasticity imaging methods rely upon accurate estimates of tissue deformation to characterize the mechanical properties of soft tissues. These methods are corrupted by clutter, which can bias and/or increase variance in displacement estimates. Harmonic imaging methods are routinely used for clutter suppression and improved image quality in conventional B-mode ultrasound, but have not been utilized in ultrasound-based elasticity imaging methods. We introduce a novel, fully-sampled pulse-inversion harmonic method for tracking tissue displacements that corrects the loss in temporal sampling frequency associated with conventional pulse-inversion techniques. The method is implemented with acoustic radiation force impulse (ARFI) imaging to monitor the displacements induced by an impulsive acoustic radiation force excitation. Custom pulse sequences were implemented on a diagnostic ultrasound scanner to collect spatially-matched fundamental and harmonic information within a single acquisition. B-mode and ARFI images created from fundamental data collected at 4 MHz and 8 MHz are compared with 8-MHz harmonic images created using a band-pass filter approach and the fully sampled pulse-inversion method. In homogeneous, tissue-mimicking phantoms, where no visible clutter was observed, there was little difference in the axial displacements, estimated jitter, and normalized cross-correlation among the fundamental and harmonic tracking methods. The similarity of the lower- and higher-frequency methods suggests that any improvement resulting from the increased frequency of the harmonic components is negligible. The harmonic tracking methods demonstrated a marked improvement in B-mode and ARFI image quality of in vivo carotid arteries. Improved feature detection and decreased variance in estimated displacements were observed in the arterial walls of harmonic ARFI images, especially in the pulse-inversion harmonic ARFI images. Within the lumen, the harmonic tracking methods improved the discrimination of the blood–vessel interface, making it easier to visualize plaque boundaries. Improvements in harmonic ARFI images in vivo were consistent with suppressed clutter supported by improved contrast and contrast-to-noise ratio (CNR) in the matched harmonic B-mode images compared with the fundamental B-mode images. These results suggest that harmonic tracking methods can improve the clinical utility and diagnostic accuracy of ultrasound-based elasticity imaging methods.

    View details for DOI 10.1109/TUFFC.2013.2831

    View details for Web of Science ID 000327729700011

    View details for PubMedID 24158290

  • SHORT-LAG SPATIAL COHERENCE IMAGING OF CARDIAC ULTRASOUND DATA: INITIAL CLINICAL RESULTS ULTRASOUND IN MEDICINE AND BIOLOGY Bell, M. A., Goswami, R., Kisslo, J. A., Dahl, J. J., Trahey, G. E. 2013; 39 (10): 1861-1874

    Abstract

    Short-lag spatial coherence (SLSC) imaging is a novel beamforming technique that reduces acoustic clutter in ultrasound images. A clinical study was conducted to investigate clutter reduction and endocardial border detection in cardiac SLSC images. Individual channel echo data were acquired from the left ventricle of 14 volunteers, after informed consent and institutional review board approval. Paired B-mode and SLSC images were created from these data. Contrast, contrast-to-noise, and signal-to-noise ratios were measured in paired images, and these metrics were improved with SLSC imaging in most cases. Three cardiology fellows rated the visibility of endocardial segments in randomly ordered B-mode and SLSC cine loops. SLSC imaging offered 22%-33% improvement (p < 0.05) in endocardial border visibility when B-mode image quality was poor (i.e., 80% or more of the endocardial segments could not be visualized by the three reviewers). The percentage of volunteers with poor-quality images was decreased from 21% to 7% with the SLSC beamformer. Results suggest that SLSC imaging has the potential to improve clinical cardiac assessments that are challenged by clutter.

    View details for DOI 10.1016/j.ultrasmedbio.2013.03.029

    View details for Web of Science ID 000324053800014

    View details for PubMedID 23932276

    View details for PubMedCentralID PMC3966558

  • Synthetic Aperture Focusing for Short-Lag Spatial Coherence Imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Bottenus, N., Byram, B. C., Dahl, J. J., Trahey, G. E. 2013; 60 (9): 1816-1826

    Abstract

    It has been demonstrated that short-lag spatial coherence (SLSC) ultrasound imaging can provide improved speckle SNR and lesion CNR compared with conventional Bmode images, especially in the presence of noise and clutter. Application of the van Cittert-Zernike theorem predicts that coherence among the ultrasound echoes received across an array is reduced significantly away from the transmit focal depth, leading to a limited axial depth of field in SLSC images. Transmit focus throughout the field of view can be achieved using synthetic aperture methods to combine multiple transmit events into a single final image. A synthetic aperture can be formed with either focused or diverging transmit beams. We explore the application of these methods to form synthetically focused channel data to create SLSC images with an extended axial depth of field. An analytical expression of SLSC image brightness through depth is derived for the dynamic receive focus case. Experimental results in a phantom and in vivo are presented and compared with dynamic receive focused SLSC images, demonstrating improved SNR and CNR away from the transmit focus and an axial depth of field four to five times longer.

    View details for DOI 10.1109/TUFFC.2013.2768

    View details for Web of Science ID 000324334900005

    View details for PubMedID 24658715

  • IN VIVO APPLICATION OF SHORT-LAG SPATIAL COHERENCE IMAGING IN HUMAN LIVER ULTRASOUND IN MEDICINE AND BIOLOGY Jakovljevic, M., Trahey, G. E., Nelson, R. C., Dahl, J. J. 2013; 39 (3): 534-542

    Abstract

    We present the results of a patient study conducted to assess the performance of two novel imaging methods, namely short-lag spatial coherence (SLSC) and harmonic spatial coherence imaging (HSCI), in an in vivo liver environment. Similar in appearance to the B-mode images, SLSC and HSCI images are based solely on the spatial coherence of fundamental and harmonic echo data, respectively, and do not depend on the echo magnitude. SLSC and HSCI suppress incoherent echo signals and thus tend to reduce clutter. The SLSC and HSCI images of 17 patients demonstrated sharper delineation of blood vessel walls, suppressed clutter inside the vessel lumen, and showed reduced speckle in surrounding tissue compared to matched B-modes. Target contrast and contrast-to-noise ratio (CNR) show statistically significant improvements between fundamental B-mode and SLSC imaging and between harmonic B-mode and HSCI imaging (in all cases p < 0.001). The magnitude of improvement in contrast and CNR increases as the overall quality of B-mode images decreases. Poor-quality fundamental B-mode images (where image quality classification is based on both contrast and CNR) exhibit the highest improvements in both contrast and CNR (288% improvement in contrast and 533% improvement in CNR).

    View details for DOI 10.1016/j.ultrasmedbio.2012.09.022

    View details for Web of Science ID 000314872200015

    View details for PubMedID 23347642

    View details for PubMedCentralID PMC3638043

  • Acoustic Radiation Force Imaging Emerging Imaging Technologies in Medicine Dahl, J. J. Taylor & Francis Group. 2013: 201–207
  • Coherent flow imaging: A power Doppler imaging technique based on backscatter spatial coherence Joint UFFC, EFTF, and PFM Symposium Dahl, J. J., Bottenus, N., Lediju Bell, M. A., Cook, M. 2013: 639–642
  • Apodization schemes for SLSC imaging: Simula- tion, phantom and in vivo demonstrations of image quality Joint UFFC, EFTF, and PFM Symposium Bottenus, N., Dahl, J. J., Trahey, G. E. 2013: 1276–1279
  • Acoustic radiation force impulse imaging (ARFI) on an IVUS circular array Joint UFFC, EFTF, and PFM Symposium Patel, V., Dahl, J., Bradway, D., Doherty, J., Lee, S. Y., Smith, S. 2013: 773–776
  • In Vivo Performance Evaluation of Short-Lag Spatial Coherence and Harmonic Spatial Coherence Imaging in Fetal Ultrasound IEEE International Ultrasonics Symposium (IUS) Kakkad, V., Dahl, J., Ellestad, S., Trahey, G. 2013: 600–603
  • Spatial coherence and its relationship to human tissue: An analytical description of imaging methods Joint UFFC, EFTF, and PFM Symposium Pinton, G., Trahey, G., Dahl, J. 2013: 569–599
  • Volumetric SLSC imaging of vasculature on a clincal matrix array Joint UFFC, EFTF, and PFM Symposium Jakovljevic, M., Byram, B. C., Dahl, J. J., Trahey, G. E. 2013: 1240–43
  • Identification and impact of blocked elements in 1-D and 2-D arrays Joint UFFC, EFTF, and PFM Symposium Jakovljevic, M., Dahl, J. J., Trahey, G. E. 2013: 1296–99
  • In vivo performance evaluation of short- lag spatial coherence (SLSC) and harmonic spatial coherence (HSC) imaging in fetal ultrasound Joint UFFC, EFTF, and PFM Symposium Kakkad, V., Dahl, J., Ellestad, S., Trahey, G. 2013: 600–603
  • In Vivo demonstration of a real-time simultaneous B-mode/spatial coherence GPU-based beamformer Joint UFFC, EFTF, and PFM Symposium Hyun, D., Trahey, G. E., Dahl, J. J. 2013: 1280–83
  • A harmonic tracking method for improved visualization of arterial structures with acoustic radiation force impulse imaging Joint UFFC, EFTF, and PFM Symposium Doherty, J., Dahl, J., Allen, J., Ham, K., Trahey, G. 2013: 1769–72
  • Harmonic Spatial Coherence Imaging: An Ultrasonic Imaging Method Based on Backscatter Coherence IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dahl, J. J., Jakovljevic, M., Pinton, G. F., Trahey, G. E. 2012; 59 (4): 648-659

    Abstract

    We introduce a harmonic version of the short-lag spatial coherence (SLSC) imaging technique, called harmonic spatial coherence imaging (HSCI). The method is based on the coherence of the second-harmonic backscatter. Because the same signals that are used to construct harmonic B-mode images are also used to construct HSCI images, the benefits obtained with harmonic imaging are also obtained with HSCI. Harmonic imaging has been the primary tool for suppressing clutter in diagnostic ultrasound imaging, however secondharmonic echoes are not necessarily immune to the effects of clutter. HSCI and SLSC imaging are less sensitive to clutter because clutter has low spatial coherence. HSCI shows favorable imaging characteristics such as improved contrast-to-noise ratio (CNR), improved speckle SNR, and better delineation of borders and other structures compared with fundamental and harmonic B-mode imaging. CNRs of up to 1.9 were obtained from in vivo imaging of human cardiac tissue with HSCI, compared with 0.6, 0.9, and 1.5 in fundamental B-mode, harmonic B-mode, and SLSC imaging, respectively. In vivo experiments in human liver tissue demonstrated SNRs of up to 3.4 for HSCI compared with 1.9 for harmonic B-mode. Nonlinear simulations of a heart chamber model were consistent with the in vivo experiments.

    View details for DOI 10.1109/TUFFC.2012.2243

    View details for Web of Science ID 000303405500004

    View details for PubMedID 22547276

    View details for PubMedCentralID PMC3342045

  • Recent Advances in Ultrasonic Imaging and Ultrasonic Imaging Technology Advances in Medical Physics – 2012 Dahl, J. J., Trahey, G. E. Medical Physics Publishing. 2012: 219–234
  • Comparative evaluation of wavefront coherence imaging methods in the presence of clutter IEEE International Ultrasonics Symposium (IUS) Dahl, J. J., Trahey, G. E. 2012: 1977–1981
  • Clinical realization of SLSC imaging on 2D arrays IEEE International Ultrasonics Symposium Jakovljevic, M., Hyun, D., Byram, B. C., Trahey, G. E., Dahl, J. J. 2012: 2266–2269
  • A harmonic tracking method for acoustic radiation force impulse (ARFI) imaging EEE International Ultrasonics Symposium (IUS) Doherty, J., Dahl, J. J., Trahey, G. E. 2012: 208–211
  • Efficient strategies for estimating spatial coherence on matrix probes IEEE International Ultrasonics Symposium Hyun, D., Trahey, G. E., Dahl, J. J. 2012: 117–120
  • Application of synthetic aperture focusing to short-lag spatial coherence IEEE International Ultrasonics Symposium (IUS) Bottenus, N., Hyun, D., Dahl, J. J., Trahey, G. E., Byram, B. C. 2012: 2262–2265
  • Improved visualization of endocardial borders with short-lag spatial coherence imaging of fundamental and harmonic ultrasound data EEE International Ultrasonics Symposium (IUS) Lediju Bell, M. A., Goswami, R., Dahl, J. J., Trahey, G. E. 2012: 2129–2132
  • The development and potential of acoustic radiation force impulse (ARFI) imaging for carotid artery plaque characterization VASCULAR MEDICINE Allen, J. D., Ham, K. L., Dumont, D. M., Sileshi, B., Trahey, G. E., Dahl, J. J. 2011; 16 (4): 302-311

    Abstract

    Stroke is the third leading cause of death and long-term disability in the USA. Currently, surgical intervention decisions in asymptomatic patients are based upon the degree of carotid artery stenosis. While there is a clear benefit of endarterectomy for patients with severe (> 70%) stenosis, in those with high/moderate (50-69%) stenosis the evidence is less clear. Evidence suggests ischemic stroke is associated less with calcified and fibrous plaques than with those containing softer tissue, especially when accompanied by a thin fibrous cap. A reliable mechanism for the identification of individuals with atherosclerotic plaques which confer the highest risk for stroke is fundamental to the selection of patients for vascular interventions. Acoustic radiation force impulse (ARFI) imaging is a new ultrasonic-based imaging method that characterizes the mechanical properties of tissue by measuring displacement resulting from the application of acoustic radiation force. These displacements provide information about the local stiffness of tissue and can differentiate between soft and hard areas. Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in their stiffness properties, they represent excellent candidates for ARFI imaging. We present information from early phantom experiments and excised human limb studies to in vivo carotid artery scans and provide evidence for the ability of ARFI to provide high-quality images which highlight mechanical differences in tissue stiffness not readily apparent in matched B-mode images. This allows ARFI to identify soft from hard plaques and differentiate characteristics associated with plaque vulnerability or stability.

    View details for DOI 10.1177/1358863X11400936

    View details for Web of Science ID 000293699400009

    View details for PubMedID 21447606

    View details for PubMedCentralID PMC3265036

  • Short-Lag Spatial Coherence of Backscattered Echoes: Imaging Characteristics IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Lediju, M. A., Trahey, G. E., Byram, B. C., Dahl, J. J. 2011; 58 (7): 1377-1388

    Abstract

    Conventional ultrasound images are formed by delay-and-sum beamforming of the backscattered echoes received by individual elements of the transducer aperture. Although the delay-and-sum beamformer is well suited for ultrasound image formation, it is corrupted by speckle noise and challenged by acoustic clutter and phase aberration. We propose an alternative method of imaging utilizing the short-lag spatial coherence (SLSC) of the backscattered echoes. Compared with matched B-mode images, SLSC images demonstrate superior SNR and contrast-to-noise ratio in simulated and experimental speckle-generating phantom targets, but are shown to be challenged by limited point target conspicuity. Matched B-mode and SLSC images of a human thyroid are presented. The challenges and opportunities of real-time implementation of SLSC imaging are discussed.

    View details for DOI 10.1109/TUFFC.2011.1957

    View details for Web of Science ID 000293688700009

    View details for PubMedID 21768022

    View details for PubMedCentralID PMC3172134

  • Lesion Detectability in Diagnostic Ultrasound with Short-Lag Spatial Coherence Imaging ULTRASONIC IMAGING Dahl, J. J., Hyun, D., Lediju, M., Trahey, G. E. 2011; 33 (2): 119-133

    Abstract

    We demonstrate a novel imaging technique, named short-lag spatial coherence (SLSC) imaging, which uses short distance (or lag) values of the coherence function of backscattered ultrasound to create images. Simulations using Field II are used to demonstrate the detection of lesions of varying sizes and contrasts with and without acoustical clutter in the backscattered data. B-mode and SLSC imaging are shown to be nearly equivalent in lesion detection, based on the contrast-to-noise ratio (CNR) of the lesion, in noise-free conditions. The CNR of the SLSC image, however, can be adjusted to achieve an optimal value at the expense of image smoothness and resolution. In the presence of acoustic clutter, SLSC imaging yields significantly higher CNR than B-mode imaging and maintains higher image quality than B-mode with increasing noise. Compression of SLSC images is shown to be required under high-noise conditions but is unnecessary under no- and low-noise conditions. SLSC imaging is applied to in vivo imaging of the carotid sheath and demonstrates significant gains in CNR as well as visualization of arterioles in the carotid sheath. SLSC imaging has a potential application to clutter rejection in ultrasonic imaging.

    View details for Web of Science ID 000291961800003

    View details for PubMedID 21710827

  • Improved detectability of hypoechoic regions with short-lag spatial coherence imaging SPIE Medical Imaging Jakovljevic, M., Dahl, J. J., Trahey, G. E. 2011
  • A novel imaging technique based on the spatial coherence of backscattered waves: Demonstration in the presence of acoustical clutter SPIE Medical Imaging Dahl, J. J., Pinton, G. F., Lediju, M., Trahey, G. E. 2011
  • Development and evaluation of pulse sequences for freehand ARFI imaging IEEE International Ultrasonics Symposium Doherty, J. R., Dumont, D. M., Hyun, D., Dahl, J. J., Trahey, G. E. 2011: 1281–1284
  • Resolution, apodization, and noise considerations in short-lag spatial coherence (SLSC) images compared to B-mode images IEEE International Ultrasonics Symposium (IUS) Lediju Bell, M. A., Dahl, J. J., Trahey, G. E. 2011
  • Characteristics of the spatial coherence function from backscattered ultrasound with phase aberration and reverberation clutter IEEE International Ultrasonics Symposium Pinton, G. F., Trahey, G. E., Dahl, J. J. 2011: 684–687
  • Comparison of ultrasonic measurements of nulliparous versus multiparous cervices IEEE International Ultrasonics Symposium (IUS) Reush, L. M., Carlson, L., Palmeri, M. L., Dahl, J. J., Feltovich, H., Hall, T. J. 2011: 1349–1352
  • In Vivo application of SLSC imaging in human liver IEEE International Ultrasonics Symposium (IUS) Jakovljevic, M., Trahey, G. E., Dahl, J. J. 2011: 2130–2133
  • Ultrasound imaging utilizing the short-lag spatial coherence of backscattered echoes IEEE International Ultrasonics Symposium Lediju, M., Byram, B. C., Trahey, G. E., Dahl, J. J. 2010: 987–990
  • The effects of image degradation on ultrasound-guided HIFU IEEE International Ultrasonics Symposium (IUS) Dahl, J. J., Pinton, G. F., Trahey, G. E. 2010: 809–812
  • Impact of the structure of subcutaneous tissue on ultrasonic clutter IEEE International Ultrasonics Symposium Dahl, J. J. 2010: 2167–2170
  • Impact of clutter levels on spatial covariance: Implications for imaging IEEE International Ultrasonics Symposium (IUS) Pinton, G. F., Dahl, J. J., Trahey, G. E. 2010: 2171–2174
  • A Motion-Based Approach to Abdominal Clutter Reduction IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Lediju, M. A., Pihl, M. J., Hsu, S. J., Dahl, J. J., Gallippi, C. M., Trahey, G. E. 2009; 56 (11): 2437-2449

    Abstract

    In ultrasound images, clutter is a noise artifact most easily observed in anechoic or hypoechoic regions. It appears as diffuse echoes overlying anatomical structures of diagnostic importance, obscuring tissue borders and reducing image contrast. A novel clutter reduction method for abdominal images is proposed, wherein the abdominal wall is displaced during successive-frame image acquisitions. A region of clutter distal to the abdominal wall was observed to move with the abdominal wall, and finite impulse response (FIR) and blind source separation (BSS) motion filters were implemented to reduce this clutter. The proposed clutter reduction method was tested in simulated and phantom data and applied to fundamental and harmonic in vivo bladder and liver images from 2 volunteers. Results show clutter reductions ranging from 0 to 18 dB in FIR-filtered images and 9 to 27 dB in BSS-filtered images. The contrast-to-noise ratio was improved by 21 to 68% and 44 to 108% in FIR- and BSS-filtered images, respectively. Improvements in contrast ranged from 4 to 12 dB. The method shows promise for reducing clutter in other abdominal images.

    View details for DOI 10.1109/TUFFC.2009.1331

    View details for Web of Science ID 000271478600012

    View details for PubMedID 19942530

    View details for PubMedCentralID PMC2835155

  • Comparison of 3-D Multi-Lag Cross-Correlation and Speckle Brightness Aberration Correction Algorithms on Static and Moving Targets IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Ivancevich, N. A., Dahl, J. J., Smith, S. W. 2009; 56 (10): 2157-2166

    Abstract

    Phase correction has the potential to increase the image quality of 3-D ultrasound, especially transcranial ultrasound. We implemented and compared 2 algorithms for aberration correction, multi-lag cross-correlation and speckle brightness, using static and moving targets. We corrected three 75-ns rms electronic aberrators with full-width at half-maximum (FWHM) auto-correlation lengths of 1.35, 2.7, and 5.4 mm. Cross-correlation proved the better algorithm at 2.7 and 5.4 mm correlation lengths (P < 0.05). Static cross-correlation performed better than moving-target cross-correlation at the 2.7 mm correlation length (P < 0.05). Finally, we compared the static and moving-target cross-correlation on a flow phantom with a skull casting aberrator. Using signal from static targets, the correction resulted in an average contrast increase of 22.2%, compared with 13.2% using signal from moving targets. The contrast-to-noise ratio (CNR) increased by 20.5% and 12.8% using static and moving targets, respectively. Doppler signal strength increased by 5.6% and 4.9% for the static and moving-targets methods, respectively.

    View details for DOI 10.1109/TUFFC.2009.1298

    View details for Web of Science ID 000270592000012

    View details for PubMedID 19942503

  • On the Feasibility of Imaging Peripheral Nerves Using Acoustic Radiation Force Impulse Imaging ULTRASONIC IMAGING Palmeri, M. L., Dahl, J. J., Macleod, D. B., Grant, S. A., Nightingale, K. R. 2009; 31 (3): 172-182

    Abstract

    Regional anesthesia is preferred over general anesthesia for many surgical procedures; however, challenges associated with poor image guidance limit its widespread acceptance as a viable alternative. In B-mode ultrasound images, the current standard for guidance, nerves can be difficult to visualize due to their similar acoustic impedance with surrounding tissues and needles must be aligned within the imaging plane at limited angles of approach that can impede successful peripheral nerve anesthesia. These challenges lead to inadequate regional anesthesia, necessitating intraoperative interventions, and can cause complications, including hemorrhage, intraneural injections and even nerve paralysis. ARFI imaging utilizes acoustic radiation force to generate images that portray relative tissue stiffness differences. Peripheral nerves are typically surrounded by many different tissue types (e.g., muscle, fat and fascia) that provide a mechanical basis for improved image contrast using ARFI imaging over conventional B-mode images. ARFI images of peripheral nerves and needles have been generated in cadaveric specimens and in humans in vivo. Contrast improvements of >600% have been achieved for distal sciatic nerve structures. The brachial plexus has been visualized with improved contrast over B-mode images in vivo during saline injection and ARFI images can delineate nerve bundle substructures to aid injection guidance. Physiologic motion during ARFI imaging of nerves near arterial structures has been successfully suppressed using ECG-triggered image acquisition and motion filters. This work demonstrates the feasibility of using ARFI imaging to improve the visualization of peripheral nerves during regional anesthesia procedures.

    View details for Web of Science ID 000269642100003

    View details for PubMedID 19771960

  • Lower-Limb Vascular Imaging with Acoustic Radiation Force Elastography: Demonstration of In Vivo Feasibility IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dumont, D., Dahl, J., Miller, E., Allen, J., Fahey, B., Trahey, G. 2009; 56 (5): 931-944

    Abstract

    Acoustic radiation force impulse (ARFI) imaging characterizes the mechanical properties of tissue by measuring displacement resulting from applied ultrasonic radiation force. In this paper, we describe the current status of ARFI imaging for lower-limb vascular applications and present results from both tissue-mimicking phantoms and in vivo experiments. Initial experiments were performed on vascular phantoms constructed with polyvinyl alcohol for basic evaluation of the modality. Multilayer vessels and vessels with compliant occlusions of varying plaque load were evaluated with ARFI imaging techniques. Phantom layers and plaque are well resolved in the ARFI images, with higher contrast than B-mode, demonstrating the ability of ARFI imaging to identify regions of different mechanical properties. Healthy human subjects and those with diagnosed lower-limb peripheral arterial disease were imaged. Proximal and distal vascular walls are well visualized in ARFI images, with higher mean contrast than corresponding B-mode images. ARFI images reveal information not observed by conventional ultrasound and lend confidence to the feasibility of using ARFI imaging during lower-limb vascular workup.

    View details for DOI 10.1109/TUFFC.2009.1126

    View details for Web of Science ID 000265371600007

    View details for PubMedID 19473912

    View details for PubMedCentralID PMC2813206

  • ACOUSTIC RADIATION FORCE IMPULSE IMAGING FOR NONINVASIVE CHARACTERIZATION OF CAROTID ARTERY ATHEROSCLEROTIC PLAQUES: A FEASIBILITY STUDY ULTRASOUND IN MEDICINE AND BIOLOGY Dahl, J. J., Dumont, D. M., Allen, J. D., Miller, E. M., Trahey, G. E. 2009; 35 (5): 707-716

    Abstract

    Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A stiff cap was observed covering the large soft tissue region, with the cap thickness ranging from 0.7-1.3 mm.

    View details for DOI 10.1016/j.ultrasmedbio.2008.11.001

    View details for Web of Science ID 000265990500001

    View details for PubMedID 19243877

    View details for PubMedCentralID PMC2813205

  • A Heterogeneous Nonlinear Attenuating Full-Wave Model of Ultrasound IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Pinton, G. F., Dahl, J., Rosenzweig, S., Trahey, G. E. 2009; 56 (3): 474-488

    Abstract

    A full-wave equation that describes nonlinear propagation in a heterogeneous attenuating medium is solved numerically with finite differences in the time domain (FDTD). Three-dimensional solutions of the equation are verified with water tank measurements of a commercial diagnostic ultrasound transducer and are shown to be in excellent agreement in terms of the fundamental and harmonic acoustic fields and the power spectrum at the focus. The linear and nonlinear components of the algorithm are also verified independently. In the linear nonattenuating regime solutions match results from Field II, a well established software package used in transducer modeling, to within 0.3 dB. Nonlinear plane wave propagation is shown to closely match results from the Galerkin method up to 4 times the fundamental frequency. In addition to thermoviscous attenuation we present a numerical solution of the relaxation attenuation laws that allows modeling of arbitrary frequency dependent attenuation, such as that observed in tissue. A perfectly matched layer (PML) is implemented at the boundaries with a numerical implementation that allows the PML to be used with high-order discretizations. A -78 dB reduction in the reflected amplitude is demonstrated. The numerical algorithm is used to simulate a diagnostic ultrasound pulse propagating through a histologically measured representation of human abdominal wall with spatial variation in the speed of sound, attenuation, nonlinearity, and density. An ultrasound image is created in silico using the same physical and algorithmic process used in an ultrasound scanner: a series of pulses are transmitted through heterogeneous scattering tissue and the received echoes are used in a delay-and-sum beam-forming algorithm to generate a images. The resulting harmonic image exhibits characteristic improvement in lesion boundary definition and contrast when compared with the fundamental image. We demonstrate a mechanism of harmonic image quality improvement by showing that the harmonic point spread function is less sensitive to reverberation clutter.

    View details for DOI 10.1109/TUFFC.2009.1066

    View details for Web of Science ID 000263479600008

    View details for PubMedID 19411208

  • Image Quality, Tissue Heating, and Frame Rate Trade-offs in Acoustic Radiation Force Impulse Imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Bouchard, R. R., Dahl, J. J., Hsu, S. J., Palmeri, M. L., Trahey, G. E. 2009; 56 (1): 63-76

    Abstract

    The real-time application of acoustic radiation force impulse (ARFI) imaging requires both short acquisition times for a single ARFI image and repeated acquisition of these frames. Due to the high energy of pulses required to generate appreciable radiation force, however, repeated acquisitions could result in substantial transducer face and tissue heating. We describe and evaluate several novel beam sequencing schemes which, along with parallel-receive acquisition, are designed to reduce acquisition time and heating. These techniques reduce the total number of radiation force impulses needed to generate an image and minimize the time between successive impulses. We present qualitative and quantitative analyses of the trade-offs in image quality resulting from the acquisition schemes. Results indicate that these techniques yield a significant improvement in frame rate with only moderate decreases in image quality. Tissue and transducer face heating resulting from these schemes is assessed through finite element method modeling and thermocouple measurements. Results indicate that heating issues can be mitigated by employing ARFI acquisition sequences that utilize the highest track-to-excitation ratio possible.

    View details for DOI 10.1109/TUFFC.2009.1006

    View details for Web of Science ID 000262561600009

    View details for PubMedID 19213633

    View details for PubMedCentralID PMC3764610

  • Acoustic radiation force impulse imaging of cardiac tissue IEEE International Ultrasonics Symposium (IUS) Trahey, G. E., Dahl, J. J., Hsu, S. J., Dumont, D. M., Bouchard, R. R., Allen, J. D., Wolf, P. D. 2009: 163–168
  • Clutter and sources of image degradation in fun- damental and harmonic ultrasound imaging IEEE International Ultrasonics Symposium (IUS) Pinton, G. F., Dahl, J. J., Trahey, G. E. 2009: 2300–2303
  • Simulation and experimental analysis of ultrasonic clutter in fundamental and harmonic imaging SPIE Medical Imaging Dahl, J. J., Pinton, G. F., Lediju, M., Trahey, G. E. 2009
  • Quantitative Assessment of the Magnitude, Impact and Spatial Extent of Ultrasonic Clutter ULTRASONIC IMAGING Lediju, M. A., Pihl, M. J., Dahl, J. J., Trahey, G. E. 2008; 30 (3): 151-168

    Abstract

    Clutter is anoise artifact in ultrasound images that appears as diffuse echoes overlying signals of interest. It is most easily observed in anechoic or hypoechoic regions, such as in cysts, blood vessels, amniotic fluid, and urine-filled bladders. Clutter often obscures targets of interest and complicates anatomical measurements. An analytical expression that characterizes the extent to which clutter degrades lesion contrast was derived and compared to the measured contrast loss due to clutter in a bladder phantom. Simulation and phantom studies were performed to determine ideal and achievable signal-to-clutter ratios. In vivo clutter magnitudes were quantified in simultaneously-acquired fundamental and harmonic bladder images from five volunteers. Clutter magnitudes ranged from -30 dB to 0 dB, relative to the mean signal of the bladder wall. For this range of clutter magnitudes, the analytical expression predicts a contrast loss of 0-45 dB for lesions with clutter-free contrasts of 6-48 dB. A pixel-wise comparison of simultaneously-acquired fundamental and harmonic bladder images from each volunteer revealed an overall signal reduction in harmonic images, with average reductions ranging from 11-18 dB in the bladder interior and 9-11 dB in the tissue surrounding the bladder. Harmonic imaging did not reduce clutter in all volunteers.

    View details for Web of Science ID 000262274000002

    View details for PubMedID 19149461

  • Quantifying hepatic shear modulus in vivo using acoustic radiation force ULTRASOUND IN MEDICINE AND BIOLOGY Palmeri, M. L., Wang, M. H., Dahl, J. J., Frinkley, K. D., Nightingale, K. R. 2008; 34 (4): 546-558

    Abstract

    The speed at which shear waves propagate in tissue can be used to quantify the shear modulus of the tissue. As many groups have shown, shear waves can be generated within tissues using focused, impulsive, acoustic radiation force excitations, and the resulting displacement response can be ultrasonically tracked through time. The goals of the work herein are twofold: (i) to develop and validate an algorithm to quantify shear wave speed from radiation force-induced, ultrasonically-detected displacement data that is robust in the presence of poor displacement signal-to-noise ratio and (ii) to apply this algorithm to in vivo datasets acquired in human volunteers to demonstrate the clinical feasibility of using this method to quantify the shear modulus of liver tissue in longitudinal studies. The ultimate clinical application of this work is noninvasive quantification of liver stiffness in the setting of fibrosis and steatosis. In the proposed algorithm, time-to-peak displacement data in response to impulsive acoustic radiation force outside the region of excitation are used to characterize the shear wave speed of a material, which is used to reconstruct the material's shear modulus. The algorithm is developed and validated using finite element method simulations. By using this algorithm on simulated displacement fields, reconstructions for materials with shear moduli (mu) ranging from 1.3-5 kPa are accurate to within 0.3 kPa, whereas stiffer shear moduli ranging from 10-16 kPa are accurate to within 1.0 kPa. Ultrasonically tracking the displacement data, which introduces jitter in the displacement estimates, does not impede the use of this algorithm to reconstruct accurate shear moduli. By using in vivo data acquired intercostally in 20 volunteers with body mass indices ranging from normal to obese, liver shear moduli have been reconstructed between 0.9 and 3.0 kPa, with an average precision of +/-0.4 kPa. These reconstructed liver moduli are consistent with those reported in the literature (mu = 0.75-2.5 kPa) with a similar precision (+/-0.3 kPa). Repeated intercostal liver shear modulus reconstructions were performed on nine different days in two volunteers over a 105-day period, yielding an average shear modulus of 1.9 +/- 0.50 kPa (1.3-2.5 kPa) in the first volunteer and 1.8 +/- 0.4 kPa (1.1-3.0 kPa) in the second volunteer. The simulation and in vivo data to date demonstrate that this method is capable of generating accurate and repeatable liver stiffness measurements and appears promising as a clinical tool for quantifying liver stiffness.

    View details for DOI 10.1016/j.ultrasmedbio.2007.10.009

    View details for Web of Science ID 000254766500005

    View details for PubMedID 18222031

    View details for PubMedCentralID PMC2362504

  • The next wave Enterprise Imaging & Therapeutic Radiology Management Dahl, J. 2008; 18 (7): 53-54
  • Magnitude, Origins, and Reduction of Abdominal Ultrasonic Clutter 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX Lediju, M. A., Pihl, M. J., Hsu, S. J., Dahl, J. J., Gallippi, C. M., Trahey, G. E. 2008: 50-53

    View details for Web of Science ID 000268845800013

  • Three-Dimensional Acoustic Radiation Force Impulse (ARFI) Imaging of Human Prostates in vivo 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX Zhai, L., Dahl, J., Madden, J., Mouraviev, V., Polascik, T., Palmeri, M., Nightingale, K. 2008: 540-543

    View details for Web of Science ID 000268845800131

  • Direction of arrival filters for improved aberration estimation ULTRASONIC IMAGING Dahl, J. J., Feehan, T. J. 2008; 30 (1): 1-20

    Abstract

    Successful adaptive imaging requires accurate measurements of the aberration profile across the array surface. Two-dimensional spatial filters are used to obtain more accurate estimates of aberrating layers by suppressing wavefronts emanating from off-axis scatterers. Application of these filters to the rf signals of the individual elements rejects wavefronts arriving from angles other than the look direction of the array and results in an increase in element-to-element correlation. Spatial filtering reduced the amount of error in the measured aberration profiles and adaptive spatial filtering further improved the estimates. The improvements in aberration estimation obtained with these methods are verified using simulations and experiments in tissue-mimicking phantoms. The technique is applied to signals obtained from in vivo human thyroid.

    View details for Web of Science ID 000256552700001

    View details for PubMedID 18564593

  • A parallel tracking method for acoustic radiation force impulse imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dahl, J. J., Pinton, G. F., Palmeri, M. L., Agrawal, V., Nightingale, K. R., Trahey, G. E. 2007; 54 (2): 301-312

    Abstract

    Radiation force-based techniques have been developed by several groups for imaging the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one such method that uses commercially available scanners to generate localized radiation forces in tissue. The response of the tissue to the radiation force is determined using conventional B-mode imaging pulses to track micron-scale displacements in tissue. Current research in ARFI imaging is focused on producing real-time images of tissue displacements and related mechanical properties. Obstacles to producing a real-time ARFI imaging modality include data acquisition, processing power, data transfer rates, heating of the transducer, and patient safety concerns. We propose a parallel receive beamforming technique to reduce transducer heating and patient acoustic exposure, and to facilitate data acquisition for real-time ARFI imaging. Custom beam sequencing was used with a commercially available scanner to track tissue displacements with parallel-receive beamforming in tissue-mimicking phantoms. Using simulations, the effects of material properties on parallel tracking are observed. Transducer and tissue heating for parallel tracking are compared to standard ARFI beam sequencing. The effects of tracking beam position and size of the tracked region are also discussed in relation to the size and temporal response of the region of applied force, and the impact on ARFI image contrast and signal-to-noise ratio are quantified.

    View details for DOI 10.1109/TUFFC.2007.244

    View details for Web of Science ID 000243920900010

    View details for PubMedID 17328327

    View details for PubMedCentralID PMC1810393

  • An ultrasound research interface for a clinical system (vol 53, pg 1759, 2006) IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Brunke, S. S., Insana, M. F., Dahl, J. J., Hansen, C., Ashfaq, M., Ermert, H. 2007; 54 (1): 198-210

    Abstract

    Under a contract with the National Cancer Institute, we have developed a research interface to an ultrasound system. This ultrasound research interface (URI) is an optional feature providing several basic capabilities not normally available on a clinical scanner. The URI can store high-quality beamformed radio-frequency data to file for off-line processing. Also, through an integrated user interface, the user is provided additional control over the B-mode receive aperture and color flow ensemble size. A third major capability is the ability to record and playback macro files. In this paper, we describe the URI and illustrate its use on three research examples: elastography, computed tomography, and spatial compounding.

    View details for DOI 10.1109/TUFFC.2007.226

    View details for Web of Science ID 000243042700021

    View details for PubMedID 17225815

  • Radiation force imaging: Challenges and opportunities MEDICAL IMAGING 2007: ULTRASONIC IMAGING AND SIGNAL PROCESSING Trahey, G. E., Palmeri, M., Nightingale, K., Dahl, J. 2007; 6513

    View details for DOI 10.1117/12.719470

    View details for Web of Science ID 000247373000012

  • Transthoracic cardiac acoustic radiation force impulse imaging: A feasibility study 2007 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1-6 Bradway, D. P., Hsu, S. J., Fahey, B. J., Dahl, J. J., Nichols, T. C., Trahey, G. E. 2007: 448-451

    View details for Web of Science ID 000254281800106

  • Clutter from multiple scattering and aberration in a nonlinear medium 2007 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1-6 Pinton, G., Dahl, J., Trahey, G. 2007: 1736-1739

    View details for Web of Science ID 000254281801185

  • On the potential for guidance of ablation therapy using acoustic radiation force impulse imaging 2007 4TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING : MACRO TO NANO, VOLS 1-3 Nightingale, K., Fahey, B., Hsu, S., Frinkley, K., Dahl, J., Palmeri, M., Zhai, L., Pinton, G., Trahey, G. 2007: 1116-1119

    View details for Web of Science ID 000252957300280

  • Clinical applications of acoustic radiation force impulse imaging 19th International Congress on Acoustics Nightingale, K., Palmeri, M., Zhai, L., Frinkley, K., Wang, M., Dahl, J., Pinton, G., Hsu, S., Fahey, B., Dumont, D., Trahey, G. 2007: 5940–5945
  • Magnitude, origins, and reduction of abdominal ultrasonic clutter IEEE Ultrasonics Symposium (IUS) Lediju, M., Pihl, M., Hsu, S., Dahl, J., Gallippi, C., Trahey, G. 2007: 50–53
  • Adaptive imaging on a diagnostic ultrasound scanner at quasi real-time rates IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dahl, J. J., McAleavey, S. A., Pinton, G. F., Soo, M. S., Trahey, G. E. 2006; 53 (10): 1832-1843

    Abstract

    Constructing an ultrasonic imaging system capable of compensating for phase errors in real-time is a significant challenge in adaptive imaging. We present a versatile adaptive imaging system capable of updating arrival time profiles at frame rates of approximately 2 frames per second (fps) with 1-D arrays and up to 0.81 fps for 1.75-D arrays, depending on the desired near-field phase correction algorithm. A novel feature included in this system is the ability to update the aberration profile at multiple beam locations for 1-D arrays. The features of this real-time adaptive imaging system are illustrated in tissue-mimicking phantoms with physical near-field phase screens and evaluated in clinical breast tissue with a 1.75-D array. The contrast-to-noise ratio (CNR) of anechoic cysts was shown to improve dramatically in the tissue-mimicking phantoms. In breast tissue, the width of point-like targets showed significant improvement: a reduction of 26.2% on average. Brightness of these targets, however, marginally decreased by 3.9%. For larger structures such as cysts, little improvement in features and CNR were observed, which is likely a result of the system assuming an infinite isoplanatic patch size for the 1.75-D arrays. The necessary requirements for constructing a real-time adaptive imaging system are also discussed.

    View details for DOI 10.1109/TUFFC.2006.115

    View details for Web of Science ID 000240860200013

    View details for PubMedID 17036791

  • Phase-aberration correction with a 3-D ultrasound scanner: Feasibility study IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Ivancevich, N. M., Dahl, J. J., Trahey, G. E., Smith, S. W. 2006; 53 (8): 1432-1439

    Abstract

    We tested the feasibility of using adaptive imaging, namely phase-aberration correction, with two-dimensional (2-D) arrays and real-time, 3-D ultrasound. Because of the high spatial frequency content of aberrators, 2-D arrays, which generally have smaller pitch and thus higher spatial sampling frequency, and 3-D imaging show potential to improve the performance of adaptive imaging. Phase-correction algorithms improve image quality by compensating for tissue-induced errors in beamforming. Using the illustrative example of transcranial ultrasound, we have evaluated our ability to perform adaptive imaging with a real-time, 3-D scanner. We have used a polymer casting of a human temporal bone, root-mean-square (RMS) phase variation of 45.0 ns, full-width-half-maximum (FWHM) correlation length of 3.35 mm, and an electronic aberrator, 100 ns RMS, 3.76 mm correlation, with tissue phantoms as illustrative examples of near-field, phase-screen aberrators. Using the multilag, least-squares, cross-correlation method, we have shown the ability of 3-D adaptive imaging to increase anechoic cyst identification, image brightness, contrast-to-speckle ratio (CSR), and, in 3-D color Doppler experiments, the ability to visualize flow. For a physical aberrator skull casting we saw CSR increase by 13% from 1.01 to 1.14, while the number of detectable cysts increased from 4.3 to 7.7.

    View details for Web of Science ID 000239405700006

    View details for PubMedID 16921895

  • Rapid tracking of small displacements with ultrasound IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Pinton, G. F., Dahl, J. J., Trahey, G. E. 2006; 53 (6): 1103-1117

    Abstract

    Time-delay estimators, such as normalized cross correlation and phase-shift estimation, form the computational basis for elastography, blood flow measurements, and acoustic radiation force impulse (ARFI) imaging. This paper examines the performance of these algorithms for small displacements (less than half the ultrasound pulse wavelength). The effects of noise, bandwidth, stationary echoes, kernel size, downsampling, interpolation, and quadrature demodulation on the accuracy of the time delay estimates are measured in terms of bias and jitter. Particular attention is given to the accuracy and resolution of the displacement measurements and to the computational efficiency of the algorithms. In most cases, Loupas' two-dimensional (2-D) autocorrelator performs as well as the gold standard, normalized cross correlation. However, Loupas' algorithm's calculation time is significantly faster, and it is particularly suited to operate on the signal data format most commonly used in ultrasound scanners. These results are used to implement a real-time ARFI imaging system using a commercial ultrasound scanner and a computer cluster. Images processed with the algorithms are examined in an ex vivo liver ablation study.

    View details for Web of Science ID 000238493000003

    View details for PubMedID 16846143

  • Phase aberration correction on a 3D ultrasound scanner using RF speckle from moving targets IEEE Ultrasonics Symposium (IUS) Ivancevich, N., Dahl, J. J., Trahey, G. E., Smith, S. W. 2006: 120–123
  • Parallel Tracking and Other Methods for Real-Time ARFI Imaging Systems 2006 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-5, PROCEEDINGS Dahl, J. J., Bouchard, R. R., Palmeri, M. L., Agrawal, V., Trahey, G. E. 2006: 1005-1008

    View details for Web of Science ID 000260407800240

  • 3D Acoustic Radiation Force Impulse (ARFI) Imaging using a 2D Matrix Array: Feasibility Study 2006 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-5, PROCEEDINGS Fronheiser, M. P., Dahl, J. J., Pinton, G. F., Chao, Z., Smith, S. W. 2006: 1144-1147

    View details for Web of Science ID 000260407800272

  • Characterization of In Vivo Atherosclerotic Plaques in the Carotid Artery with Acoustic Radiation Force Impulse Imaging 2006 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-5, PROCEEDINGS Dahl, J. J., Dumont, D. M., Miller, E. M., Schwark, E., Allen, J. D., Trahey, G. E. 2006: 706-709

    View details for Web of Science ID 000260407800169

  • Shear Wave Velocity Estimation Using Acoustic Radiation Force Impulsive Excitation in Liver In Vivo 2006 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-5, PROCEEDINGS Nightingale, K. R., Zhai, L., Dahl, J. J., Frinkley, K. D., Palmeri, M. L. 2006: 1156-1160

    View details for Web of Science ID 000260407800275

  • Spatial and temporal aberrator stability for real-time adaptive imaging IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dahl, J. J., Soo, M. S., Trahey, G. E. 2005; 52 (9): 1504-1517

    Abstract

    Reported real-time adaptive imaging systems use near-field phase correction techniques, which are desired because of their simple implementation and their compatibility with current system architectures. Aberrator stability is important to adaptive imaging because it defines the spatial and temporal limits for which the near-field phase estimates are valid. Spatial aberrator stability determines the required spatial sampling of the aberrator, and temporal aberrator stability determines the length of time for which the aberration profile can be used. In this study, the spatial and temporal stability of clinically measured aberrations is reported for breast, liver, and thyroid tissue. Cross correlations between aberration estimates revealed aberrators to have azimuthal isoplanatic patch sizes of 0.44, 0.28, and 0.20 mm for breast, liver, and thyroid tissue, respectively, at 80% correlation. Axial isoplanatic patch sizes were 1.26, 0.76, and 1.80 mm for the same tissue, respectively, at 80% correlation. Temporal stability at 80% correlation was determined to be greater than 1.5 seconds for breast and thyroid tissue, and 0.65 seconds for the liver. The effects of noise, motion, and target nonuniformity on aberrator stability are characterized by simulations and experiments in tissue mimicking phantoms.

    View details for Web of Science ID 000232420000010

    View details for PubMedID 16285449

  • Adaptive imaging and spatial compounding in the presence of aberration IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Dahl, J. J., Guenther, D. A., Trahey, G. E. 2005; 52 (7): 1131-1144

    Abstract

    Spatial compounding reduces speckle and increases image contrast by incoherently averaging images acquired at different viewing angles. Adaptive imaging improves contrast and resolution by compensating for tissue-induced phase errors. Aberrator strength and spatial frequency content markedly impact the desirable operating characteristics and performance of these methods for improving image quality. Adaptive imaging, receive-spatial compounding, and a combination of these two methods are presented in contrast and resolution tasks under various aberration characteristics. All three imaging methods yield increases in the contrast-to-noise ratio (CNR) of anechoic cysts; however, the improvements vary depending on the properties of the aberrating layer. Phase correction restores image spatial frequencies, and the addition of compounding opposes the restoration of image spatial frequencies. Lesion signal-to-noise ratio (SNR), an image quality metric for predicting lesion detectability, shows that combining spatial compounding with phase correction yields the maximum detectability when the aberrator strength or spatial frequency content is high. Examples of these modes are presented in thyroid tissue.

    View details for Web of Science ID 000231186900008

    View details for PubMedID 16212252

  • Ultrasonic beamforming and image formation Categorical Course in Diagnostic Radiology Physics: Multidimensional Image Processing, Analysis, and Display Dahl, J. 2005: 63-71
  • Real-time acoustic radiation force impulse imaging MEDICAL IMAGING 2005: ULTRASONIC IMAGING AND SIGNAL PROCESSING Pinton, G. F., McAleavey, S. A., Dahl, J. J., Nightingale, K. R., Trahey, G. E. 2005; 5750: 226-235

    View details for DOI 10.1117/12.595846

    View details for Web of Science ID 000229069500025

  • Phase correction of skull aberration with 1.75-D and 2-D Arrays using speckle targets 2005 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 Dahl, J. J., Ivancevich, N. A., Keen, C. G., Trahey, G. E., Smith, S. W. 2005: 1323-1326

    View details for Web of Science ID 000236090701147

  • Rapid tracking of small displacements using ultrasound 2005 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 Pinton, G. F., Dahl, J. J., Trahey, G. E. 2005: 2062-2065

    View details for Web of Science ID 000236090703049

  • Clinical evaluation of combined spatial compounding and adaptive imaging in breast tissue ULTRASONIC IMAGING Dahl, J. J., Soo, M. S., Trahey, G. E. 2004; 26 (4): 203-216

    Abstract

    When spatial compounding is applied to targets with significant acoustic velocity inhomogeneities, the correlation between speckle patterns of the images to be averaged decreases, thereby increasing the speckle reduction nominally obtained. Phase correction applied to these targets improves the coherence of the wavefield and restores image spatial frequencies. Combining these two modes can be used to effectively increase the contrast-to-noise ratio (CNR) of imaging targets and improve the general image quality of these targets over spatial compounding alone. This paper presents a clinical evaluation of combined spatial compounding and adaptive imaging in breast tissue and compares this combined technique to conventional imaging and to adaptive imaging and spatial compounding operating independently. Experiments were performed on a 1.75-D, 8 x 96 array attached to a commercially-available scanner. Cysts, microcalcifications and other breast structures were targeted in order to assess the impact of the combined mode on CNR, target width, target brightness and target peak-to-background ratio (PBR). In general, phase correction improved cyst CNR by 7.7%, decreased target width by 18.7%, increased target brightness by 30.1% and increased PBR by 17.9%. Compounding alone, using three overlapping 9.71 mm subapertures, increased cyst CNR by 24.6%, but increased target width by 25.4% and decreased PBR by 13.2%. Combining both modes, however, increased cyst CNR by 32.6%, inappreciably increased target width by 1.1% and marginally decreased PBR by 2.8%. The increase in target brightness with this combined mode was 20.0%

    View details for Web of Science ID 000232346800001

    View details for PubMedID 15864979

  • Real time 3D ultrasound imaging of the brain 2004 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-3 Ivancevich, N. M., Chu, K. K., Dahl, J. D., Light, E. D., Trahey, G. E., Idriss, S. F., Wolf, P. D., Dixon-Tulloch, E., Smith, S. W. 2004: 110-113

    View details for Web of Science ID 000228557207028

  • Spatial and temporal stability of tissue induced aberration 2004 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-3 Dahl, J. J., Soo, M. S., Trahey, G. E. 2004: 222-226

    View details for Web of Science ID 000228557207055

  • Resolution improvement of point targets by real-time phase aberration correction: in vivo results 2004 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-3 McAleavey, S. A., Dahl, J. J., Soo, M. S., Pinton, G. F., Trahey, G. E. 2004: 235-238

    View details for Web of Science ID 000228557207058

  • Synthetic elevation beamforming and image acquisition capabilities using an 8 x 128 1.75D array IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Fernandez, A. T., Gammelmark, K. L., Dahl, J. J., Keen, C. G., Gauss, R. C., Trahey, G. E. 2003; 50 (1): 40-57

    Abstract

    Ultrasound imaging can be improved with higher order arrays through elevation dynamic focusing in future, higher channel count systems. However, modifications to current system hardware could yield increased imaging depth-of-field with 1.75D arrays (arrays with individually addressable elements, several rows in elevation) through the use of synthetic elevation imaging. We describe synthetic elevation beamforming methods and its implementation with our 8 x 128, 1.75D array (Tetrad Co., Englewood, CO). This array has been successfully interfaced with a Siemens Elegra scanner for summed RF and single channel RF data acquisition. Individual rows of the 8 x 128 array can be controlled, allowing for different aperture configurations on transmit and receive beamforming. Advantages of using this array include finer elevation sampling, a larger array footprint for aberration measurements, and elevation focusing. We discuss system tradeoffs that occur in implementing synthetic receive and synthetic transmit/receive elevation focusing and show significant image quality improvements in simulation and phantom data results.

    View details for Web of Science ID 000180768900004

    View details for PubMedID 12578135

  • Real time adaptive imaging with 1.75D, high frequency arrays 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 McAleavey, S. A., Dahl, J. J., Pinton, G. F., Trahey, G. E. 2003: 335-338

    View details for Web of Science ID 000189492100073

  • Off-axis scatterer filters for improved aberration measurements 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Dahl, J. J., Trahey, G. E. 2003: 343-347

    View details for Web of Science ID 000189492100075

  • Performance evaluation of spatial compounding in the presence of aberration and adaptive Imaging Medical Imaging 2003 Conference Dahl, J. J., Guenther, D., Trahey, G. E. SPIE-INT SOC OPTICAL ENGINEERING. 2003: 1–11

    View details for Web of Science ID 000183593400001

  • Performance evaluation of combined spatial compounding/adaptive imaging: Simulation, phantom and clinical trials 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Dahl, J. J., Guenther, D., Trahey, G. E. 2003: 1532-1536

    View details for Web of Science ID 000189492100353

  • Arterial stiffness measurements with acoustic radiation force impulse imaging Medical Imaging 2003 Conference Trahey, G. E., Dahl, J. J., McAleavey, S. A., Gallippi, C. M., Nightingale, K. R. SPIE-INT SOC OPTICAL ENGINEERING. 2003: 235–241

    View details for Web of Science ID 000183593400026

  • Shear Wave Anisotropy Imaging 2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Hsu, S. J., Palermi, M. L., Nightingale, K. R., McAleavey, S. A., Dahl, J. D., Trahey, G. E. 2003: 921-924

    View details for Web of Science ID 000189492100206

  • Array elevation requirements in phase aberration correction using an 8x128 1.75D array MEDICAL IMAGE 2002: ULTRASONIC IMAGING AND SIGNAL PROCESSING Fernandez, A. T., Dahl, J. J., Dumont, D. N., Trahey, G. E. 2002; 4687: 79-90

    View details for Web of Science ID 000176292800008

  • Acoustic radiation force impulse imaging: Remote palpation of the mechanical properties of tissue 2002 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Nightingale, K., Soo, M. S., Nightingale, R., Bentley, R., Stutz, D., Palmeri, M., Dahl, J., Trahey, G. 2002: 1821-1830

    View details for Web of Science ID 000182111700410

  • High resolution ultrasound beamforming using synthetic and adaptive imaging techniques 2002 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING, PROCEEDINGS Fernandez, A. T., Dahl, J. J., Gammelmark, K., Dumont, D. M., Trahey, G. E. 2002: 433-436

    View details for Web of Science ID 000178000400109

  • Aberration measurement and correction with a high resolution 1.75D array 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 Fernandez, A. T., Dahl, J. J., Dumont, D. M., Trahey, G. E. 2001: 1489-1494

    View details for Web of Science ID 000176890800327