Publications

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  • Applications of PET-MRI in musculoskeletal disease. Journal of magnetic resonance imaging : JMRI Kogan, F., Broski, S. M., Yoon, D., Gold, G. E. 2018; 48 (1): 27–47

    Abstract

    New integrated PET-MRI systems potentially provide a complete imaging modality for diagnosis and evaluation of musculoskeletal disease. MRI is able to provide excellent high-resolution morphologic information with multiple contrast mechanisms that has made it the imaging modality of choice in evaluation of many musculoskeletal disorders. PET offers incomparable abilities to provide quantitative information about molecular and physiologic changes that often precede structural and biochemical changes. In combination, hybrid PET-MRI can enhance imaging of musculoskeletal disorders through early detection of disease as well as improved diagnostic sensitivity and specificity. The purpose of this article is to review emerging applications of PET-MRI in musculoskeletal disease. Both clinical applications of malignant musculoskeletal disease as well as new opportunities to incorporate the molecular capabilities of nuclear imaging into studies of nononcologic musculoskeletal disease are discussed. Lastly, we discuss some of the technical considerations and challenges of PET-MRI as they specifically relate to musculoskeletal disease.LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2018;48:27-47.

    View details for DOI 10.1002/jmri.26183

    View details for PubMedID 29969193

  • Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report JOURNAL OF PAIN RESEARCH Cipriano, P., Lee, S., Yoon, D., Shen, B., Tawfik, V., Curtin, C., Dragoo, J. L., James, M., Mccurdy, C., Chin, F., Biswal, S. 2018; 11: 2353–56

    Abstract

    The ability to accurately diagnose and objectively localize pain generators in chronic pain sufferers remains a major clinical challenge since assessment relies on subjective patient complaints and relatively non-specific diagnostic tools. Developments in clinical molecular imaging, including advances in imaging technology and radiotracer design, have afforded the opportunity to identify tissues involved in pain generation based on their pro-nociceptive condition. The sigma-1 receptor (S1R) is a pro-nociceptive receptor upregulated in painful, inflamed tissues, and it can be imaged using the highly specific radioligand 18F-FTC-146 with PET.A 50-year-old woman with a 7-year history of refractory, left-knee pain of unknown origin was referred to our pain management team. Over the past several years, she had undergone multiple treatments, including a lateral retinacular release, radiofrequency ablation of a peripheral nerve, and physical therapy. While certain treatments provided partial relief, her pain would inevitably return to its original state. Using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with the novel radiotracer 18F-FTC-146, imaging showed increased focal uptake of 18F-FTC-146 in the intercondylar notch, corresponding to an irregular but equivocal lesion identified in the simultaneously acquired MRI. These imaging results prompted surgical removal of the lesion, which upon resection was identified as an inflamed, intraarticular synovial lipoma. Removal of the lesion relieved the patient's pain, and to date the pain has not recurred.We present a case of chronic, debilitating knee pain that resolved with surgery following identification of the pathology with a novel clinical molecular imaging approach that detects chronic pain generators at the molecular and cellular level. This approach has the potential to identify and localize pain-associated pathology in a variety of chronic pain syndromes.

    View details for DOI 10.2147/JPR.S167839

    View details for Web of Science ID 000447159100003

    View details for PubMedID 30349360

    View details for PubMedCentralID PMC6190812

  • SNR-weighted regularization of ADC estimates from double-echo in steady-state (DESS). Magnetic resonance in medicine Sveinsson, B., Gold, G. E., Hargreaves, B. A., Yoon, D. 2018

    Abstract

    To improve the homogeneity and consistency of apparent diffusion coefficient (ADC) estimates in cartilage from the double-echo in steady-state (DESS) sequence by applying SNR-weighted regularization during post-processing.An estimation method that linearizes ADC estimates from DESS is used in conjunction with a smoothness constraint to suppress noise-induced variation in ADC estimates. Simulations, phantom scans, and in vivo scans are used to demonstrate how the method reduces ADC variability. Conventional diffusion-weighted echo-planar imaging (DW EPI) maps are acquired for comparison of mean and standard deviation (SD) of the ADC estimate.Simulations and phantom scans demonstrated that the SNR-weighted regularization can produce homogenous ADC maps at varying levels of SNR, whereas non-regularized maps only estimate ADC accurately at high SNR levels. The in vivo maps showed that the SNR-weighted regularization produced ADC maps with similar heterogeneity to maps produced with standard DW EPI, but without the distortion of such reference scans.A linear approximation of a simplified model of the relationship between DESS signals allows for fast SNR-weighted regularization of ADC maps that reduces estimation error in relatively short T2 tissue such as cartilage.

    View details for DOI 10.1002/mrm.27436

    View details for PubMedID 30125389

  • F-FTC-146 in humans. Journal of nuclear medicine Hjørnevik, T., Cipriano, P. W., Shen, B., Hyung Park, J., Gulaka, P., Holley, D., Gandhi, H., Yoon, D., Mittra, E. S., Zaharchuk, G., Gambhir, S. S., McCurdy, C. R., Chin, F. T., Biswal, S. 2017

    Abstract

    The purpose of this study is to assess safety, biodistribution and radiation dosimetry in humans for the highly selective sigma-1 receptor (S1R) positron emission tomography (PET) agent (18)F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ((18)F-FTC-146). Methods: Ten healthy volunteers (HV; five female, five male; age: 34.3 ± 6.5 years) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/magnetic resonance imaging (PET/MRI) examinations were acquired for up to three hours after injection (357.2 ± 48.8 MBq). Blood samples were collected and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions-of-interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry was estimated using PMOD 3.7 and Organ Linear Internal Dose Assessment (OLINDA). Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to (18)F-FTC-146 were reported. High accumulation of (18)F-FTC-146 was observed in S1R dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose (ED) of (18)F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range: 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade (18)F-FTC-146 were successful. Injection of (18)F-FTC-146 is safe, and absorbed doses are acceptable. The potential of (18)F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.

    View details for DOI 10.2967/jnumed.117.192641

    View details for PubMedID 28572487

  • Metallic Implant Geometry and Susceptibility Estimation Using Multispectral B-0 Field Maps MAGNETIC RESONANCE IN MEDICINE Shi, X., Yoon, D., Koch, K. M., Hargreaves, B. A. 2017; 77 (6): 2402-2413

    Abstract

    To estimate the susceptibility and the geometry of metallic implants from multispectral imaging (MSI) information, to separate the metal implant region from the surrounding signal loss region.The susceptibility map of signal-void regions is estimated from MSI B0 field maps using total variation (TV) regularized inversion. Voxels with susceptibility estimates above a predetermined threshold are identified as metal. The accuracy of the estimated susceptibility and implant geometry was evaluated in simulations, phantom, and in vivo experiments.The proposed method provided more accurate susceptibility estimation compared with a previous method without TV regularization, in both simulations and phantom experiments. In the phantom experiment where the actual implant was 40% of the signal-void region, the mean estimated susceptibility was close to the susceptibility in literature, and the precision and recall of the estimated geometry was 85% and 93%. In vivo studies in subjects with hip implants also demonstrated that the proposed method can distinguish implants from surrounding low-signal tissues, such as cortical bone.The proposed method can improve the delineation of metallic implant geometry by distinguishing metal voxels from artificial signal voids and low-signal tissues by estimating the susceptibility maps. Magn Reson Med 77:2402-2413, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26313

    View details for Web of Science ID 000401270900031

  • 2D multi-spectral imaging for fast MRI near metal. Magnetic resonance in medicine Hargreaves, B. A., Taviani, V., Litwiller, D. V., Yoon, D. 2017

    Abstract

    To develop a fast 2D method for MRI near metal with reduced B0 in-plane and through-slice artifacts.Multi-spectral imaging (MSI) approaches reduce artifacts in MR images near metal, but require 3D imaging of multiple excited volumes regardless of imaging geometry or artifact severity. The proposed 2D MSI method rapidly excites a limited slice and spectral region using gradient reversal between excitation and refocusing pulses, then uses standard 2D imaging, with the process repeating to cover multiple spectral offsets that are combined as in other MSI techniques. 2D MSI was implemented in a spin-echo-train sequence and validated in phantoms and in vivo by comparing it with standard spin-echo imaging and existing MSI techniques.2D MSI images for each spatial-spectral region follow isocontours of the dipole-like B0 field variation, and thus frequency variation, near metal devices. Artifact correction in phantoms and human subjects with metal is comparable to 3D MSI methods, and superior to standard spin-echo techniques. Scan times are reduced compared with 3D MSI methods in cases where a limited number of slices are needed, though signal-to-noise ratio is also reduced as expected.2D MSI offers a fast and flexible alternative to 3D MSI for artifact reduction near metal. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26724

    View details for PubMedID 28444805

  • F]FTC-146. Molecular imaging and biology Shen, B., Park, J. H., Hjørnevik, T., Cipriano, P. W., Yoon, D., Gulaka, P. K., Holly, D., Behera, D., Avery, B. A., Gambhir, S. S., McCurdy, C. R., Biswal, S., Chin, F. T. 2017

    Abstract

    Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [(18)F]FTC-146, demonstrated high affinity for the S1R (K i = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; K i = 364 nM) across several species (from mouse to non-human primate). Herein, we report the clinical-grade radiochemistry filed with exploratory Investigational New Drug (eIND) and first-in-human PET/MRI evaluation of [(18)F]FTC-146.[(18)F]FTC-146 is prepared via a direct [(18)F] fluoride nucleophilic radiolabeling reaction and formulated in 0.9 % NaCl containing no more than 10 % ethanol through sterile filtration. Quality control (QC) was performed based on USP 823 before doses were released for clinical use. The safety and whole body biodistribution of [(18)F]FTC-146 were evaluated using a simultaneous PET/MR scanner in two representative healthy human subjects.[(18)F]FTC-146 was synthesized with a radiochemical yield of 3.3 ± 0.7 % and specific radioactivity of 8.3 ± 3.3 Ci/μmol (n = 10, decay corrected to EOB). Both radiochemical and chemical purities were >95 %; the prepared doses were stable for 4 h at ambient temperature. All QC test results met specified clinical criteria. The in vivo PET/MRI investigations showed that [(18)F]FTC-146 rapidly crossed the blood brain barrier and accumulated in S1R-rich regions of the brain. There were also radioactivity distributed in the peripheral organs, i.e., the lungs, spleen, pancreas, and thyroid. Furthermore, insignificant uptake of [(18)F]FTC-146 was observed in cortical bone and muscle.A reliable and automated radiosynthesis for providing routine clinical-grade [(18)F]FTC-146 for human studies was established in a modified GE TRACERlab FXFN. PET/MRI demonstrated the initial tracer biodistribution in humans, and clinical studies investigating different S1R-related diseases are in progress.

    View details for DOI 10.1007/s11307-017-1064-z

    View details for PubMedID 28280965

  • Feasibility of 7T MRI for Imaging Fascicular Structures of Peripheral Nerves. Muscle & nerve Yoon, D., Biswal, S., Rutt, B., Lutz, A., Hargreaves, B. 2017

    Abstract

    Evaluation of the nerve fascicular structure can be useful in diagnosing nerve damage, but it is a very challenging task with 3T MRI due to limited resolution. In this pilot study, we present the feasibility of high-resolution 7T MRI for examining the nerve fascicular structure.A 3D gradient-spoiled sequence was used for imaging peripheral nerves in extremities. Images acquired with different in-plane resolutions (0.42 x 0.42mm vs. 0.12 x 0.12mm), and different main field strengths (7T vs. 3T) were compared.The individual nerve fascicles were identified at 0.12 x 0.12mm resolution in both field strengths, but not at 0.42 x 0.42mm resolution. The fascicular structure was more sharply depicted in 7T images than in 3T images.High-resolution 3D imaging with 7T MRI demonstrated feasibility in imaging nerve fascicular structures. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/mus.26035

    View details for PubMedID 29211916

  • 18F-FDG PET/MRI in Chronic Sciatica: Early Results Revealing Spinal and Non-spinal Abnormalities. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Cipriano, P., Yoon, D., Gandhi, H., Holley, D., Thakur, D., Ith, M., Hargreaves, B., Kennedy, D., Smuck, M., Cheng, I., Biswal, S. 2017

    Abstract

    Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the offending pathology remains challenging. In this report, the feasibility of a fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) approach for improved diagnosis of chronic sciatica is presented. Methods:18F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers. Region-of-interest analysis using maximum standardized uptake values (SUVmax) was performed, and 18F-FDG uptake in lesions was compared with the corresponding areas in healthy controls. Results: Significantly increased 18F-FDG uptake was observed in detected lesions of all patients, which was correlated with pain symptoms. 18F-FDG-avid lesions were not only found in impinged spinal nerves, but were also associated with non-spinal causes, such as a facet joint degeneration, pars defect, or a presumed scar neuroma. Conclusion: The feasibility of 18F-FDG PET/MRI for diagnosing pain generators in chronic sciatica has been demonstrated, revealing various possible etiologies.

    View details for DOI 10.2967/jnumed.117.198259

    View details for PubMedID 29097408

  • Prolongation of ERP latency and reaction time (RT) in simultaneous EEG/fMRI data acquisition JOURNAL OF NEUROSCIENCE METHODS Chun, J., Peltier, S. J., Yoon, D., Manschreck, T. C., Deldin, P. J. 2016; 268: 78-86

    Abstract

    Recording EEG and fMRI data simultaneously inside a fully-operating scanner has been recognized as a novel approach in human brain research. Studies have demonstrated high concordance between the EEG signals and hemodynamic response. However, a few studies reported altered cognitive process inside the fMRI scanner such as delayed reaction time (RT) and reduced and/or delayed N100 and P300 event-related brain potential (ERP) components.The present study investigated the influence of electromagnetic field (static magnetic field, radio frequency (RF) pulse, and gradient switching) and experimental environment on posterior N100 and P300 ERP components in four different settings with six healthy subjects using a visual oddball task: (1) classic fMRI acquisition inside the scanner (e.g., supine position, mirror glasses for stimulus presentation), (2) standard behavioral experiment outside the scanner (e.g., seated position, keyboard response), (3) controlled fMRI acquisition inside the scanner (e.g., organic light-emitting diode (OLED) goggles for stimulus presentation) inside; and (4) modified behavioral experiment outside the scanner (e.g., supine position, OLED goggles).The study findings indicated that the experimental environment in simultaneous EEG/fMRI acquisition could substantially delay N1P, P300 latency, and RT inside the scanner, and was associated with a reduced N1P amplitude.There was no effect of electromagnetic field in the prolongation of RT, N1P and P300 latency inside the scanner. N1P, but not P300, latency was sensitive to stimulus presentation method inside the scanner.Future simultaneous EEG/fMRI data collection should consider experimental environment in both design and analysis.

    View details for DOI 10.1016/j.jneumeth.2016.05.011

    View details for Web of Science ID 000379104400010

    View details for PubMedID 27172845

  • MR thermometry near metallic devices using multispectral imaging. Magnetic resonance in medicine Weber, H., Taviani, V., Yoon, D., Ghanouni, P., Pauly, K. B., Hargreaves, B. A. 2016

    Abstract

    The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.26203

    View details for PubMedID 26991803

  • Small-tip fast recovery imaging using non-slice-selective tailored tip-up pulses and radiofrequency-spoiling MAGNETIC RESONANCE IN MEDICINE Nielsen, J., Yoon, D., Noll, D. C. 2013; 69 (3): 657-666

    Abstract

    Small-tip fast recovery (STFR) imaging is a new steady-state imaging sequence that is a potential alternative to balanced steady-state free precession. Under ideal imaging conditions, STFR may provide comparable signal-to-noise ratio and image contrast as balanced steady-state free precession, but without signal variations due to resonance offset. STFR relies on a tailored "tip-up," or "fast recovery," radiofrequency pulse to align the spins with the longitudinal axis after each data readout segment. The design of the tip-up pulse is based on the acquisition of a separate off-resonance (B0) map. Unfortunately, the design of fast (a few ms) slice- or slab-selective radiofrequency pulses that accurately tailor the excitation pattern to the local B0 inhomogeneity over the entire imaging volume remains a challenging and unsolved problem. We introduce a novel implementation of STFR imaging based on "non-slice-selective" tip-up pulses, which simplifies the radiofrequency pulse design problem significantly. Out-of-slice magnetization pathways are suppressed using radiofrequency-spoiling. Brain images obtained with this technique show excellent gray/white matter contrast, and point to the possibility of rapid steady-state T(2)/T(1) -weighted imaging with intrinsic suppression of cerebrospinal fluid, through-plane vessel signal, and off-resonance artifacts. In the future, we expect STFR imaging to benefit significantly from parallel excitation hardware and high-order gradient shim systems.

    View details for DOI 10.1002/mrm.24289

    View details for Web of Science ID 000315331300006

    View details for PubMedID 22511367

    View details for PubMedCentralID PMC3408566

  • Fast joint design method for parallel excitation radiofrequency pulse and gradient waveforms considering off-resonance MAGNETIC RESONANCE IN MEDICINE Yoon, D., Fessler, J. A., Gilbert, A. C., Noll, D. C. 2012; 68 (1): 278-285

    Abstract

    A fast parallel excitation pulse design algorithm to select and to order phase-encoding (PE) locations (also known as "spokes") of an Echo-Volumar excitation k-space trajectory considering B(0) field inhomogeneity is presented. Recently, other groups have conducted research to choose optimal PE locations, but the potential benefit of considering B(0) field inhomogeneity during PE location selection or their ordering has not been fully investigated. This article introduces a novel fast greedy algorithm to determine PE locations and their order that takes into account the off-resonance effects. Computer simulations of the proposed algorithm for B(1) field inhomogeneity correction demonstrate that it not only improves excitation accuracy but also provides an effective ordering of the PE locations.

    View details for DOI 10.1002/mrm.24311

    View details for Web of Science ID 000305119100029

    View details for PubMedID 22555857

    View details for PubMedCentralID PMC3939078

  • Spectral-Spatial Pulse Design for Through-Plane Phase Precompensatory Slice Selection in T-2(star)-Weighted Functional MRI MAGNETIC RESONANCE IN MEDICINE Yip, C., Yoon, D., Olafsson, V., Lee, S., Grissom, W. A., Fessler, J. A., Noll, D. C. 2009; 61 (5): 1137-1147

    Abstract

    T(2)*-weighted functional MR images suffer from signal loss artifacts caused by the magnetic susceptibility differences between air cavities and brain tissues. We propose a novel spectral-spatial pulse design that is slice-selective and capable of mitigating the signal loss. The two-dimensional spectral-spatial pulses create precompensatory phase variations that counteract through-plane dephasing, relying on the assumption that resonance frequency offset and through-plane field gradient are spatially correlated. The pulses can be precomputed before functional MRI experiments and used repeatedly for different slices in different subjects. Experiments with human subjects showed that the pulses were effective in slice selection and loss mitigation at different brain regions.

    View details for DOI 10.1002/mrm.21938

    View details for Web of Science ID 000265566000017

    View details for PubMedID 19267346

    View details for PubMedCentralID PMC2856348