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.

Clinical Focus

  • Diagnostic Radiology

Academic Appointments

  • Assistant Professor - University Medical Line, Radiology
  • Member, Bio-X

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)

Professional Education

  • Residency: UCSD Dept of Radiology (2018) CA
  • Board Certification: American Board of Radiology, Nuclear Radiology (2021)
  • Board Certification: American Board of Radiology, Diagnostic Radiology (2019)
  • Fellowship: Stanford University Radiology Fellowships (2019) CA
  • Internship: Summa Health at Akron General Internal Medicine and Preliminary Year Training (2013) OH
  • Medical Education: Case Western Reserve School of Medicine (2012) OH
  • 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.

Clinical Interests

- 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

Clinical Trials

  • Diabetes RElated to Acute Pancreatitis and Its Mechanisms Recruiting

    The overriding objective of DREAM is to conduct a prospective longitudinal (36 months) observational clinical study to investigate the incidence, etiology, and pathophysiology of diabetes mellitus (DM) following acute pancreatitis (AP).

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  • Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants With Crohn's Disease (CD) Recruiting

    The purpose of this study is to evaluate the combined remission of complex perianal fistulas, defined as the clinical assessment at Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections greater than (>) 2 centimeter (cm) (in at least 2 dimensions) confirmed by blinded central magnetic resonance imaging (MRI) assessment at Week 24.

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  • Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal Cancer Not Recruiting

    The purpose of the research is to evaluate whether both chemotherapy and radiotherapy can lead to higher rates of clinical complete response leading to organ preservation in human subjects with cancer. The objective is to learn if this treatment approach may safely be used as an alternative to the standard treatment for rectal cancer and to know the quality-of-life in these patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact Eleanor Brown, 650-724-4606.

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All Publications

  • MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients. European radiology Düx, D. M., Baal, J. D., Bitton, R., Chen, J., Brunsing, R. L., Sheth, V. R., Rosenberg, J., Kim, K., Ozhinsky, E., Avedian, R., Ganjoo, K., Bucknor, M., Dobrotwir, A., Ghanouni, P. 2023


    To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids.A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded.The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns.MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis.Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely.• Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

    View details for DOI 10.1007/s00330-023-10073-9

    View details for PubMedID 37615768

  • Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons. AJR. American journal of roentgenology Gurland, B. H., Khatri, G., Ram, R., Hull, T. L., Kocjancic, E., Quiroz, L. H., Sayed, R. F., Jambhekar, K. R., Chernyak, V., Paspulati, R. M., Sheth, V. R., Steiner, A. M., Kamath, A., Shobeiri, S. A., Weinstein, M. M., Bordeianou, L., Members of the Expert Workgroup on Magnetic Resonance Imaging of Pelvic Floor Disorders, Ayscue, J., Basilio, P., Chernyak, V., El Sayed, R. F., Gurland, B., Hall, C., Herrmann, K., Jambhekar, K., Kaiser, A. M., Kamath, A., Khatri, G., Kocjancic, E., Rafatzand, K., Rodriguez, L. M., Mishra, K., Neshatian, L., O'Neill, E., Parlade, A., Paspulati, R. M., Ram, R., Sheth, V., Steiner, A., Syan, R., Traugott, A. 2021: 1-13


    The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.

    View details for DOI 10.2214/AJR.21.26488

    View details for PubMedID 34505543

  • Increased Grades of Rectal Intussusception: Role of Decline in Pelvic Floor Integrity and Association with Dyssynergic Defecation. The American journal of gastroenterology Neshatian, L., Triadafilopoulos, G., Wallace, S., Jawahar, A., Sheth, V., Shen, S., Gurland, B. 2023


    The natural history of rectal intussusception (RI) is poorly understood. We hypothesized that decline in pelvic floor integrity and function leads to increasing RI grades.Retrospective analysis of a registry of patients with defecatory disorders with high-resolution anorectal manometry and MR defecography. Association of risk factors on increasing RI grades was assessed using logistic regression.Analysis included a total of 238 women; 90 had no RI, 43 Oxford 1-2, 49 Oxford 3, and 56 Oxford 4-5. Age (p:0.017), vaginal delivery (p: 0.008), and prior pelvic surgery (p: 0.032) were associated with increased Oxford grades. Obstructive defecation symptoms and dyssynergic defecation were observed at relatively high rates across groups. Increased RI grades was associated with less anal relaxation at simulated defecation yet, higher rates of normal balloon expulsion (p<0.05), linked to diminished anal sphincter. Indeed, increased RI grades was associated with worsening fecal incontinence severity, attributed to higher rates of anal hypotension.Levator ani laxity, defined by increased levator hiatus length and its excessive descent at straining, was associated with increasing RI grades, independent of age, history of vaginal delivery, and pelvic surgeries and could independently predict increased RI grades. Concurrent anterior and posterior compartments, and visceral prolapse were associated with higher Oxford grades.Our data suggests that decline in pelvic floor integrity with abnormal levator ani laxity is associated with increased RI grades; a process that is independent of age, history of vaginal deliveries and/or pelvic surgeries, and perhaps related to dyssynergic defecation.

    View details for DOI 10.14309/ajg.0000000000002605

    View details for PubMedID 37975595

  • Parametric Response Mapping of Co-Registered Ivim MRI and PET to Identify Radioresistant Sub-Volumes in Locally Advanced Cervical Carcinoma Undergoing CCRT. International journal of radiation oncology, biology, physics Capaldi, D. P., Wang, J. Y., Liu, L., Sheth, V., Kidd, E. A., Hristov, D. H. 2023; 117 (2S): e648


    PURPOSE/OBJECTIVE(S): To investigate parametric response mapping (PRM) of co-registered positron emission tomography (PET) and intravoxel incoherent motion (IVIM) MRI in locally advanced cervical carcinoma patients to identify sub-volumes that may predict treatment response to adjuvant concurrent chemoradiation therapy (CCRT).MATERIALS/METHODS: Pre- and on-treatment (after four weeks of CCRT) diffusion weighted images (DWIs) MRI and pre-treatment PET were performed on 20 cervical cancer patients (median [range] age: 63 [41 to 85]; FIGO staging: 3 IIB, 1 IIIB, 10 IIIC1, 4 IIIC2, 2 IVA; histology: 11 squamous cell carcinoma, 4 endocervical adenocarcinoma; LN status: 4 negative, 16 positive). IVIM MRI maps were generated by Bayesian fitting of a two-compartment IVIM model to the DWIs to produce three-dimensional diffusion coefficient (D) and perfusion fraction (f). Three-dimensional IVIM D and f maps were co-registered to PET standardized uptake value (SUV) maps. Population means of PET SUV, IVIM D and f from pre-treatment scans were calculated to generate thresholds to identify low versus high metabolic (muSUV) regions, low versus high diffused (muD) regions as well as low versus high perfused (muf) regions, respectively. PRM maps were generated using voxel-wise joint histogram analysis to classify voxels within the tumor as highly metabolic and with low cellular density (SUVD), highly metabolic and with high cellular density (SUVD), metabolically inactive and with high cellular density (SUVD), or metabolically inactive and with low cellular density (SUVD) tissue based on the population mean thresholds. Similar PRM maps were generated using the joint histogram analysis with SUV and f. Summary statistics for these and other imaging parameters were calculated pre- and on-treatment. Univariate analysis was performed to determine relationships between relative change in gross tumor volume (DeltaGTV) and pre-treatment imaging measurements.RESULTS: In tumors, on- versus pre-treatment tumor volume (p<.001) significantly decreased, while IVIM f (p = .002) and D (p = .03) significantly increased. Pre-treatment tumor volume (r = .45, p = .04) and PRM SUVD (r = .65, p = .002) regions were positively related with DeltaGTV, while pre-treatment IVIM D (r = -.64, p = .002), PRM SUVf (r = -.52, p = .02) and PRM SUVD (r = -.74, p<.001) regions were negatively related with DeltaGTV. The latter PRM result suggests that larger regions of low cellular density (as represented by elevated D) + low metabolism result in a reduced change in tumor volume on-treatment, potentially representing a radioresistant sub-volume.CONCLUSION: PRM, generated from PET and IVIM MRI, was applied to patients with locally advanced cervical carcinoma and radioresistant sub-volumes were identified which may predict treatment response. The complementary information provided from PET and IVIM, combined using PRM, may assist in decision-making to individualize therapies, such as with image guided brachytherapy, to improve patient outcomes.

    View details for DOI 10.1016/j.ijrobp.2023.06.2067

    View details for PubMedID 37785926

  • Anorectal manometry for the diagnosis of pelvic floor disorders in patients with hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome. BMC gastroenterology Zhou, W., Zikos, T. A., Halawi, H., Sheth, V. R., Gurland, B., Nguyen, L. A., Neshatian, L. 2022; 22 (1): 538


    INTRODUCTION: Functional gastrointestinal disorders (FGID) including impaired rectal evacuation are common in patients with Hypermobility Spectrum Disorder (HSD) or Hypermobile Ehlers-Danlos Syndrome (hEDS). The effect of connective tissue pathologies on pelvic floor function in HSD/hEDS remains unclear. We aimed to compare clinical characteristics and anorectal pressure profile in patients with HSD/hEDS to those of age and sex matched controls.METHODS: We conducted a retrospective review of all FGID patients who underwent high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) for evaluation of impaired rectal evacuation. Patients with HSD/hEDS were age and sex matched to a randomly selected cohort of control patients without HSD/hEDS. An abnormal BET was defined as the inability to expel a rectal balloon within 2minutes. Wilcoxon rank sum test and Fisher's exact test were used to make comparisons and logistic regression model for predictive factors for abnormal evacuation.RESULTS: A total of 144 patients (72 with HSD/hEDS and 72 controls) were analyzed. HSD/hEDS patients were more likely to be Caucasian (p<0.001) and nulliparous. Concurrent psychiatric disorders; depression, and anxiety (p<0.05), and somatic syndromes; fibromyalgia, migraine and sleep disorders (p<0.001) were more common in these patients. Rate of abnormal BET were comparable among the groups. HDS/hEDS patients had significantly less anal relaxation and higher residual anal pressures during simulated defecation, resulting in significantly more negative rectoanal pressure gradient. The remaining anorectal pressure profile and sensory levels were comparable between the groups. While diminished rectoanal pressure gradient was the determinant of abnormal balloon evacuation in non HSD/hEDS patients, increased anal resting tone and maximum volume tolerated were independent factors associated with an abnormal BET in HSD/hEDS patients. Review of defecography data from a subset of patients showed no significant differences in structural pathologies between HSD/hEDS and non HSD/hEDS patients.CONCLUSIONS: These results suggest anorectal pressure profile is not compromised by connective tissue pathologies in HSD patients. Whether concurrent psychosomatic disorders or musculoskeletal involvement impact the pelvic floor function in these patients needs further investigation.

    View details for DOI 10.1186/s12876-022-02572-8

    View details for PubMedID 36564719

  • Predictive Value of Clinical Complete Response after Chemoradiation for Rectal Cancer Liu, C., Boncompagni, A. A., Perrone, K., Agarwal, A., Hur, D. G., Lopez, I., Sheth, V., Morris, A. M. LIPPINCOTT WILLIAMS & WILKINS. 2022: S51-S52
  • Rectosigmoid Cancer-Rectal Cancer or Sigmoid Cancer? American journal of clinical oncology Hui, C., Baclay, R., Liu, K., Sandhu, N., Loo, P., von Eyben, R., Chen, C., Sheth, V., Vitzthum, L., Chang, D., Pollom, E. 2022


    OBJECTIVES: We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).MATERIALS AND METHODS: We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using chi2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.RESULTS: One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).CONCLUSIONS: Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.

    View details for DOI 10.1097/COC.0000000000000931

    View details for PubMedID 35848736

  • Editorial for "Amide Proton Transfer-Weighted Imaging Combined With Intravoxel Incoherent Motion for Evaluating Microsatellite Instability in Endometrial Cancer". Journal of magnetic resonance imaging : JMRI Sheth, V. R. 2022

    View details for DOI 10.1002/jmri.28302

    View details for PubMedID 35713324

  • Phase II trial of organ preservation program using short-course radiation and folfoxiri for rectal cancer (SHORT-FOX) Pollom, E. L., Shelton, A., Fisher, G. A., Bien, J., King, D., Johnson, T., Chen, C., Shaheen, S., Chong, C., Vitzthum, L., Kirilcuk, N., Morris, A. M., Kin, C., Dawes, A., Sheth, V., Sundaram, V., Brown, E., Chang, D. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Establishment of Patient-derived Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumor Models For Predicting Therapeutic Response. Clinical cancer research : an official journal of the American Association for Cancer Research Yebra, M., Bhargava, S., Kumar, A., Burgoyne, A. M., Tang, C., Yoon, H., Banerjee, S., Aguilera, J., Cordes, T., Sheth, V., Noh, S., Ustoy, R., Li, S., Advani, S. J., Corless, C. L., Heinrich, M. C., Kurzrock, R., Lippman, S. M., Fanta, P. T., Harismendy, O., Metallo, C., Sicklick, J. K. 2021


    PURPOSE: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e. 150-200/year) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKIs). Lack of human models for any SDH-mutant tumors, including GIST, has limited molecular characterization and drug discovery.EXPERIMENTAL DESIGN: We describe methods for establishing novel patient-derived SDH-mutant (mSDH) GIST models and interrogated the efficacy of temozolomide on these tumor models in vitro and in clinical trials of mSDH GIST patients.RESULTS: Molecular and metabolic characterization of our patient-derived mSDH GIST models revealed that these models recapitulate the transcriptional and metabolic hallmarks of parent tumors and SDH-deficiency. We further demonstrate that temozolomide elicits DNA damage and apoptosis in our mSDH GIST models. Translating our in vitro discovery to the clinic, a cohort of SDH-mutant GIST patients treated with temozolomide (n=5) demonstrated a 40% objective response rate and 100% disease control rate suggesting that temozolomide represents a promising therapy for this subset of GIST.CONCLUSION: We report the first methods to establish patient-derived mSDH tumor models, which can be readily employed for understanding patient-specific tumor biology and treatment strategies. We also demonstrate that temozolomide is effective in mSDH GIST patients who are refractory to existing chemotherapeutic drugs (namely TKIs) in clinic for GISTs, bringing a promising treatment option for these patients to clinic.

    View details for DOI 10.1158/1078-0432.CCR-21-2092

    View details for PubMedID 34426440

  • Adult residual rectourethral fistula and diverticulum presenting decades after imperforate anus repair: acase report. Journal of medical case reports McShane, E. K., Gurland, B., Sheth, V. R., Bruzoni, M., Enemchukwu, E. 2021; 15 (1): 370


    BACKGROUND: This report describes a rare surgical case of an intraabdominal mass in a middle-aged patient 40years after imperforate anus repair.CASE PRESENTATION: A 44-year-old Latino male with history of repaired anorectal malformation presented with recurrent urinary tract infections and rectal prolapse with bothersome bleeding and fecal incontinence. During his preoperative evaluation, he was initially diagnosed with a prostatic utricle cyst on the basis of magnetic resonance imaging findings, which demonstrated a cystic, thick-walled mass with low signal contents that extended inferiorly to insert into the distal prostatic urethra. However, at the time of surgical resection, the thick-walled structure contained an old, firm fecaloma. The final pathology report described findings consistent with colonic tissue, suggesting a retained remnant of the original fistula and diverticulum.CONCLUSIONS: Although rare, persistent rectourethral fistula tracts and rectal diverticula after imperforate anus repair can cause symptoms decades later, requiring surgical intervention. This is an important diagnostic consideration for any adult patient with history of imperforate anus.

    View details for DOI 10.1186/s13256-021-02921-3

    View details for PubMedID 34261520

  • Multimodal imaging assessment and histologic correlation of the female rat pelvic floor muscles' anatomy. Journal of anatomy Sheth, V. R., Duran, P., Wong, J., Shah, S., Du, J., Christman, K. L., Chang, E. Y., Alperin, M. 2019; 234 (4): 543-550


    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

  • 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 Chen, F. n., Cheng, J. Y., Taviani, V. n., Sheth, V. R., Brunsing, R. L., Pauly, J. M., Vasanawala, S. S. 2019


    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 Yuan, J. n., Hu, Y. n., Menini, A. n., Sandino, C. M., Sandberg, J. n., Sheth, V. n., Moran, C. J., Alley, M. n., Lustig, M. n., Hargreaves, B. n., Vasanawala, S. n. 2019


    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

  • Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study. Magnetic resonance imaging He, Q., Ma, Y., Fan, S., Shao, H., Sheth, V., Bydder, G. M., Du, J. 2017; 39: 194-199


    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 Sheth, V. R., Fan, S., He, Q., Ma, Y., Annese, J., Switzer, R., Corey-Bloom, J., Bydder, G. M., Du, J. 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. NeuroImage Sheth, V., Shao, H., Chen, J., Vandenberg, S., Corey-Bloom, J., Bydder, G. M., Du, J. 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. PloS one Du, J., Sheth, V., He, Q., Carl, M., Chen, J., Corey-Bloom, J., Bydder, G. M. 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 Yoo, B., Sheth, V. R., Howison, C. M., Douglas, M. J., Pineda, C. T., Maine, E. A., Baker, A. F., Pagel, M. D. 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

  • Measuring in vivo tumor pHe with CEST-FISP MRI. Magnetic resonance in medicine Sheth, V. R., Li, Y., Chen, L. Q., Howison, C. M., Flask, C. A., Pagel, M. D. 2012; 67 (3): 760-8


    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

  • Improved pH measurements with a single PARACEST MRI contrast agent. Contrast media & molecular imaging Sheth, V. R., Liu, G., Li, Y., Pagel, M. D. 2012; 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

  • Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. Molecular imaging Liu, G., Li, Y., Sheth, V. R., Pagel, M. D. 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

  • A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity. Contrast media & molecular imaging Li, Y., Sheth, V. R., Liu, G., Pagel, M. D. 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. Tetrahedron letters Yoo, B., Sheth, V. R., Pagel, M. D. 2009; 50 (31): 4459-4462


    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 Sheth, V. R., van Heeckeren, R. C., Wilson, A. G., van Heeckeren, A. M., Pagel, M. D. 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