Vipul Sheth is an Assistant Professor in the Department of Radiology. He became interested in translational research as an undergraduate studying biomedical engineering at Case Western Reserve University. He subsequently earned his MD and PhD as part of the Case Western Reserve University Medical Scientist Training program. During his PhD dissertation he investigated measurement of pH in tumor models using a MRI contrast mechanism known as Paramagnetic Chemical Exchange Saturation Transfer (PARACEST). During radiology residency at the University of California at San Diego, he investigated new applications of the ultrashort echo time MRI technique in the brain for the evaluation of myelin in patients with cystic fibrosis. He subsequently completed a fellow ship in Body MRI at Stanford before joining the faculty in 2019.
Assistant Professor - Med Center Line, Radiology
Honors & Awards
Dean’s High Honors List, Case Western Reserve University (2000-2004)
Department Stores National Merit Scholarship, Case Western Reserve University (2000-2004)
Ohio Acadamic Scholarship, Case Western Reserve University (2000-2004)
Whitaker Case Summer Research Fellow, Department of Biomedical Engineering, Case Western Reserve University (2001)
ISMRM Education Stipend Award to Present Poster, 17th International Society for Magnetic Resonance in Medicine (ISMRM), Honolulu, Hawaii (2009)
Student Stipend Travel Award to Present Poster, World Molecular Imaging Congress (WMIC), Montreal Canada (2009)
First Place Poster for Akron General Medical Center, NEOMED Internal Med. Residency Research Day, Rootstown, Ohio (2013)
AUR Scholar Program Participant, AUR Annual Meeting, Baltimore, Maryland (2014)
ISMRM Trainee Stipend Award to Present, 23rd International Society for Magnetic Resonance in Medicine (ISMRM), Milan, Italy (2014)
Robert R Mattrey Clinician-Scientist Award, Department of Radiology, University of California San Diego (2018)
Member, Academy Council for Early Career Investigators in Imaging (CECl2) (2020)
Boards, Advisory Committees, Professional Organizations
Member, International Society for Magnetic Resonance in Medicine (2008 - Present)
Member, Radiological Society of North America (2010 - Present)
Member, California Medical Association (2013 - Present)
Member, Society for Nuclear Medicine and Molecular Imaging (2016 - Present)
Member, Society for Advanced Body Imaging (2019 - Present)
Member, Society for Abdominal Radiology (2019 - Present)
Diplomate, American Board Radiology (2019)
Body MRI Fellowship, Stanford University (2019)
Clinician Scientist, Radiology Research Residency, University of California, San Diego (2018)
Transition Year Residency, Akron General Medical Center, Akron, OH (2013)
M.D. & Ph.D., Medical Scientist Training Program, Case Western Reserve University, Cleveland, OH (2012)
B.S.E., Biomedical Engineering, Case Western Reserve University, Cleveland, OH (2008)
Current Research and Scholarly Interests
My interests are in the development and translation of imaging technologies geared toward disease detection and characterization to better guide prognosis, treatment, and improve outcomes. I’m interested in supporting the development of MRI guided focal therapy methods which can personalize treatment and reduce the risk of morbidity from more invasive therapies.
- MRI for diagnosis of pelvic floor disorders
- MRI and PET/MRI to pelvic malignancies and lymph node staging.
- Whole Body MRI
- MRI guided procedures including biopsies, cryoablation, and high intensity focused ultrasound.
Translational Research Interests
- Development and translation of magnetic resonance imaging technologies to improve both diagnostics and therapeutics
- Molecular imaging and characterization of the tumor microenvironment
- Ultrashort echo time MRI applications in the body
- Developing synergistic MRI methods to complement PET in potential applications for PET/MRI
Improved pH measurements with a single PARACEST MRI contrast agent.
Contrast media & molecular imaging
; 7 (1): 26–34
The measurement of extracellular pH has potential utility for assessing the therapeutic effects of pH-dependent and pH-altering therapies. A PARAmagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agent, Yb-DO3A-oAA, has two CEST effects that are dependent on pH. A ratio derived from these CEST effects was linearly correlated with pH throughout the physiological pH range. The pH can be measured with a precision of 0.21 pH units and an accuracy of 0.09 pH units. The pH measurement is independent of concentration and T₁ relaxation times, but is dependent on temperature. Although MR coalescence affects the CEST measurements, especially at high pH, the ratiometric analysis of the CEST effects can account for incomplete saturation of the agent's amide and amine that results from MR coalescence. Provided that an empirical calibration is determined with saturation conditions, magnetic field strength and temperature that can be used for subsequent studies, these results demonstrate that this single PARACEST MRI contrast agent can accurately measure pH.
View details for DOI 10.1002/cmmi.460
View details for PubMedID 22344877
View details for PubMedCentralID PMC4882612
Data-driven self-calibration and reconstruction for non-cartesian wave-encoded single-shot fast spin echo using deep learning.
Journal of magnetic resonance imaging : JMRI
Current self-calibration and reconstruction methods for wave-encoded single-shot fast spin echo imaging (SSFSE) requires long computational time, especially when high accuracy is needed.To develop and investigate the clinical feasibility of data-driven self-calibration and reconstruction of wave-encoded SSFSE imaging for computation time reduction and quality improvement.Prospective controlled clinical trial.With Institutional Review Board approval, the proposed method was assessed on 29 consecutive adult patients (18 males, 11 females, range, 24-77 years).A wave-encoded variable-density SSFSE sequence was developed for clinical 3.0T abdominal scans to enable 3.5× acceleration with full-Fourier acquisitions. Data-driven calibration of wave-encoding point-spread function (PSF) was developed using a trained deep neural network. Data-driven reconstruction was developed with another set of neural networks based on the calibrated wave-encoding PSF. Training of the calibration and reconstruction networks was performed on 15,783 2D wave-encoded SSFSE abdominal images.Image quality of the proposed data-driven approach was compared independently and blindly with a conventional approach using iterative self-calibration and reconstruction with parallel imaging and compressed sensing by three radiologists on a scale from -2 to 2 for noise, contrast, sharpness, artifacts, and confidence. Computation time of these two approaches was also compared.Wilcoxon signed-rank tests were used to compare image quality and two-tailed t-tests were used to compare computation time with P values of under 0.05 considered statistically significant.An average 2.1-fold speedup in computation was achieved using the proposed method. The proposed data-driven self-calibration and reconstruction approach significantly reduced the perceived noise level (mean scores 0.82, P < 0.0001).The proposed data-driven calibration and reconstruction achieved twice faster computation with reduced perceived noise, providing a fast and robust self-calibration and reconstruction for clinical abdominal SSFSE imaging.1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019.
View details for DOI 10.1002/jmri.26871
View details for PubMedID 31322799
Near-silent distortionless DWI using magnetization-prepared RUFIS.
Magnetic resonance in medicine
To develop a near-silent and distortionless DWI (sd-DWI) sequence using magnetization-prepared rotating ultrafast imaging sequence.A rotating ultrafast imaging sequence was modified with driven-equilibrium diffusion preparation, including eddy-current compensation methods. To compensate for the T1 recovery during readout, a phase-cycling method was used. Both compensation methods were validated in phantoms. The optimized sequence was compared with an EPI diffusion sequence for image distortion, contrast, ADC, and acoustic noise level in phantoms. The sequence was evaluated in 1 brain volunteer, 5 prostate volunteers, and 10 pediatric patients with joint diseases.Combination of several eddy-current compensation methods reduced the artifact to an acceptable level. Phase cycling reduced T1 recovery contamination during readout. In phantom scans, the optimized sequence generated similar image contrast to the EPI diffusion sequence, and ADC maps between the sequences were comparable; sd-DWI had significantly lower acoustic noise (P < .05). In vivo brain scan showed reduced image distortion in sd-DWI compared with the EPI diffusion, although residual motion artifact remains due to brain pulsation. The prostate scans showed that sd-DWI can provide similar ADC compared with EPI diffusion, with no image distortion. Patient scans showed that the sequence can clearly depict joint lesions.An sd-DWI sequence was developed and optimized. Compared with conventional EPI diffusion, sd-DWI provided similar diffusion contrast, accurate ADC measurement, improved image quality, and minimal ambient scanning noise. The sequence showed the ability to obtain in vivo diffusion contrast in relatively motion-free body regions, such as prostate and joint.
View details for DOI 10.1002/mrm.28106
View details for PubMedID 31782557
Multimodal imaging assessment and histologic correlation of the female rat pelvic floor muscles' anatomy.
Journal of anatomy
2019; 234 (4): 543–50
Pelvic floor disorders negatively impact millions of women worldwide. Although there is a strong epidemiological association with childbirth, the mechanisms leading to the dysfunction of the integral constituents of the female pelvic floor, including pelvic floor skeletal muscles, are not well understood. This is in part due to the constraints associated with directly probing these muscles, which are located deep in the pelvis. Thus, experimental models and non-invasive techniques are essential for advancing knowledge of various phenotypes of pelvic floor muscle injury and pathogenesis of muscle dysfunction, as well as developing minimally invasive approaches for the delivery of novel therapeutics. The most widely used animal model for pelvic floor disorders is the rat. However, the radiological anatomy of rat pelvic floor muscles has not been described. To remedy this gap, the current study provides the first detailed description of the female rat pelvic floor muscles' radiological appearance on MR and ultrasound images, validated by correlation with gross anatomy and histology. We also demonstrate that ultrasound guidance can be used to target rat pelvic floor muscles for possible interventional therapies.
View details for DOI 10.1111/joa.12943
View details for PubMedID 30740685
View details for PubMedCentralID PMC6422690
Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study.
Magnetic resonance imaging
2017; 39: 194–99
In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2 water protons. Magnitude and phase imaging and T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D2O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ~300μs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from -7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTE sequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.
View details for DOI 10.1016/j.mri.2017.02.009
View details for PubMedID 28219648
View details for PubMedCentralID PMC5503674
Inversion recovery ultrashort echo time magnetic resonance imaging: A method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain - A feasibility study.
Magnetic resonance imaging
2017; 38: 87–94
Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (<1ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3T scanner. The technique was first validated on a synthetic myelin phantom (myelin powder in D2O) and a Feridex iron phantom. This was followed by studies of cadaveric MS specimens, healthy volunteers and MS patients. UTE imaging of the synthetic myelin phantom showed an excellent bi-component signal decay with two populations of protons, one with a T2* of 1.2ms (residual water protons) and the other with a T2* of 290μs (myelin protons). IR-UTE imaging shows sensitivity to a wide range of iron concentrations from 0.5 to ~30mM. The IR-UTE signal from white matter of the brain of healthy volunteers shows a rapid signal decay with a short T2* of ~300μs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter.
View details for DOI 10.1016/j.mri.2016.12.025
View details for PubMedID 28038965
View details for PubMedCentralID PMC5503675
Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies.
2016; 136: 37–44
Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR-UTE sequences at different TEs. T2* values of ~110-330μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS.
View details for DOI 10.1016/j.neuroimage.2016.05.012
View details for PubMedID 27155128
View details for PubMedCentralID PMC4914437
Measurement of T1 of the ultrashort T2* components in white matter of the brain at 3T.
2014; 9 (8): e103296
Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32 ± 0.09 ms, and a short mean T1 of 226 ± 46 ms were demonstrated for the healthy volunteers at 3T.
View details for DOI 10.1371/journal.pone.0103296
View details for PubMedID 25093859
View details for PubMedCentralID PMC4122467
Detection of in vivo enzyme activity with CatalyCEST MRI.
Magnetic resonance in medicine
2014; 71 (3): 1221–30
CatalyCEST MRI compares the detection of an enzyme-responsive chemical exchange saturation transfer (CEST) agent with the detection of an unresponsive "control" CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI.CEST agents that were responsive and unresponsive to the activity of urokinase plasminogen activator were shown to have negligible interaction with each other. A CEST-fast imaging with steady state precession (FISP) MRI protocol was used to acquire MR CEST spectroscopic images with a Capan-2 pancreatic tumor model after intravenous injection of the CEST agents. A function of (super)-Lorentzian line shapes was fit to CEST spectra of a region-of-interest that represented the tumor.The CEST effects from each agent showed the same initial uptake into tumor tissues, indicating that both agents had the same pharmacokinetic transport rates. Starting 5 min after injection, CEST from the enzyme-responsive agent disappeared more quickly than CEST from the unresponsive agent, indicating that the enzyme responsive agent was being catalyzed by urokinase plasminogen activator, while both agents also experienced net pharmacokinetic washout from the tumor.CatalyCEST MRI demonstrates that dynamic tracking of enzyme-responsive and unresponsive CEST agents during the same in vivo MRI study is feasible.
View details for DOI 10.1002/mrm.24763
View details for PubMedID 23640714
View details for PubMedCentralID PMC3742626
Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent.
2012; 11 (1): 47–57
The measurement of extracellular pH (pHe) has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI) contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST) was designed to measure tumor pH(e) throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb(3+)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid,10-o-aminoanilide (Yb-DO3A-oAA) suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST) effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.
View details for PubMedID 22418027
View details for PubMedCentralID PMC4876950
Measuring in vivo tumor pHe with CEST-FISP MRI.
Magnetic resonance in medicine
2012; 67 (3): 760–68
Paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents have been developed that can measure pH in solution studies, but these agents have not previously been detected in vivo. To use the PARACEST agent Yb-DO3A-oAA to measure the extracellular pH (pHe) in tumor tissue, a chemical exchange saturation transfer fast imaging with steady state precession MRI protocol was developed, the saturation period was optimized for sensitive chemical exchange saturation transfer (CEST) detection, and median filtering was used to remove artifacts in CEST spectra. These improvements were used to correlate pH with a ratio of two CEST effects of Yb-DO3A-oAA at a 7 T magnetic field strength (R(2) = 0.99, standard deviation of precision = 0.011 pH units). The PARACEST agent could not be detected in tumor tissue following i.v. injection due to the low sensitivity of in vivo CEST MRI. Yb-DO3A-oAA was detected in tumor tissue and leg muscle after directly injecting the PARACEST agent into these tissues. The measured CEST effects were used to measure a tumor pH of 6.82 ± 0.21 and a leg muscle pH of 7.26 ± 0.14, and parametric pH maps were also generated from these tissue regions. These results demonstrated that tumor pHe can be measured with a PARACEST agent and a rapid CEST-MRI protocol.
View details for DOI 10.1002/mrm.23038
View details for PubMedID 22028287
View details for PubMedCentralID PMC3572795
A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity.
Contrast media & molecular imaging
2010; 6 (4): 219–28
The CEST effect of many PARACEST MRI contrast agents changes in response to a molecular biomarker. However, other molecular biomarkers or environmental factors can influence CEST, so that a change in CEST is not conclusive proof for detecting the biomarker. To overcome this problem, a second control CEST effect may be included in the same PARACEST agent, which is responsive to all factors that alter the first CEST effect except for the biomarker to be measured. To investigate this approach, a PARACEST MRI contrast agent was developed with one CEST effect that is responsive to esterase enzyme activity and a second control CEST effect. The ratio of the two CEST effects was independent of concentration and T(1) relaxation, so that this agent was self-calibrating with respect to these factors. This ratiometric method was dependent on temperature and was influenced by MR coalescence as the chemical exchange rates approached the chemical shifts of the exchangable protons as temperature was increased. The two CEST effects also showed evidence of having different pH dependencies, so that this agent was not self-calibrating with respect to pH. Therefore, a self-calibrating PARACEST MRI contrast agent can more accurately detect a molecular biomarker such as esterase enzyme activity, as long as temperature and pH are within an acceptable physiological range and remain constant.
View details for DOI 10.1002/cmmi.421
View details for PubMedID 21861282
View details for PubMedCentralID PMC4879975
An amine-derivatized, DOTA-loaded polymeric support for Fmoc Solid Phase Peptide Synthesis.
2009; 50 (31): 4459–62
An amine-derivatized DOTA has been used to modify the surface of a polymeric support for conventional Solid Phase Peptide Synthesis (SPPS) following standard Fmoc chemistry methods. This methodology was used to synthesize a peptide-DOTA conjugate that was demonstrated to be a PARACEST MRI contrast agent. Therefore, this synthesis methodology can facilitate Fmoc SPPS of molecular imaging contrast agents.
View details for DOI 10.1016/j.tetlet.2009.05.061
View details for PubMedID 20161272
View details for PubMedCentralID PMC2702766
Monitoring infection and inflammation in murine models of cystic fibrosis with magnetic resonance imaging.
Journal of magnetic resonance imaging : JMRI
2008; 28 (2): 527–32
To evaluate magnetic resonance imaging (MRI) in assessing lung inflammation longitudinally in genetic mouse models of cystic fibrosis (CF). MRI is used to view soft tissues noninvasively, but the lung is challenging to image.Cftr(+/+) (wildtype) and Cftr(-/-) (CF) mice were inoculated with agarose beads laden with Pseudomonas aeruginosa. Longitudinal MR lung images were acquired with cardiac gating. The effects of echo time and respiration gating were evaluated to improve the detection of lung inflammation.Cardiac gating and signal averaging sufficiently suppressed motion artifacts without requiring respiration gating. MRI detected moderate to severe inflammation in infected mice, which was confirmed by histology results.In vivo longitudinal MRI methods can assess lung inflammation in P. aeruginosa-infected mice, which obviates serial sacrifice. MRI was able to detect inflammation in the absence of other physiological symptoms.
View details for DOI 10.1002/jmri.21440
View details for PubMedID 18666218
View details for PubMedCentralID PMC2538376