Administrative Appointments

  • Director of Resident Education, Division of Adult Neuro-Oncology, Stanford University School of Medicine Department of Neurology and Neurological Sciences (2020 - Present)
  • Diversity, Inclusion, Belonging, Equity, and Justice (DIBEJ) Committee, Stanford University Wu Tsai Neurosciences Institute (2020 - Present)
  • Fellowship Program Director, Division of Adult Neuro-Oncology, Stanford University School of Medicine Department of Neurology and Neurological Sciences (2021 - Present)

Honors & Awards

  • 40 Under 40 in Cancer: Rising Stars and Emerging Leaders, Lynx Group, Upstream Partners, Swim Across America, NCODA
  • Dee S. and Patricia Osborne Endowed Scholarship in the Neurosciences, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
  • Diversity Recognition Award, Johns Hopkins University Diversity Leadership Council
  • Excellence in Medicine Leadership Award, American Medical Association Foundation
  • Honors Scholar in Medical Education, Stanford University School of Medicine Teaching and Mentoring Academy
  • Martin Luther King, Jr. Award for Community Service, Johns Hopkins University
  • Palatucci Advocacy Leadership Forum, American Academy of Neurology
  • Student Travel Stipend Award, World Molecular Imaging Congress
  • Young Investigator Palatucci Research Award, California Neurology Society
  • Young Investigators Forum in Neuro-Oncology, Society for Neuro-Oncology (SNO) and WebMD/prIME Oncology

Boards, Advisory Committees, Professional Organizations

  • Network of Digital Health Experts Member, U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) (2020 - Present)
  • Steering Committee Member, Brain Tumor Working Group (BTWG) of the Physical Sciences Oncology Network (PSON) / Cancer Systems Biology Consortium (CSBC) (2019 - Present)
  • Associate Member Council (AMC), American Association for Cancer Research (AACR) (2018 - 2020)
  • Member, American Society of Clinical Oncology (ASCO) (2016 - Present)
  • Member, American Association for Cancer Research (AACR) (2016 - Present)
  • Member, Society for Neuro-Oncology (SNO) (2014 - Present)
  • Member, Sigma Xi (2005 - Present)
  • Member, American Academy of Neurology (AAN) (2005 - Present)
  • Member, American Physician Scientists Association (APSA) (2005 - Present)

Professional Education

  • Clinical Fellowship, Stanford University School of Medicine Department of Neurology & Neurological Sciences, Neuro-Oncology
  • Postdoctoral Fellowship, Stanford University School of Medicine Department of Radiology, Multimodal Molecular Imaging
  • Residency, University of California at Los Angeles David Geffen School of Medicine Department of Neurology, Adult Neurology
  • Internship, East Tennessee State University James H. Quillen College of Medicine Department of Internal Medicine, Internal Medicine
  • MD, University of Texas at Houston John P. and Kathrine G. McGovern Medical School, Medicine
  • PhD, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Biomedical Sciences
  • MSE, Johns Hopkins University, Biomedical Engineering
  • BS, Johns Hopkins University, Biomedical Engineering (concentration in Electrical and Computer Engineering)

Community and International Work

  • Stanford Research Experience for Community College (SRECC) Students

    Ongoing Project


    Opportunities for Student Involvement


  • Arbor Free Clinic Specialty Service (Neurology), Menlo Park VA Hospital

    Partnering Organization(s)

    VA Palo Alto Health Care System, Menlo Park Division

    Populations Served

    Uninsured patients

    Ongoing Project


    Opportunities for Student Involvement


  • Clinical Neurology Clerkship Bedside Teaching, Stanford Hospital

    Partnering Organization(s)

    Stanford University School of Medicine Department of Neurology and Neurological Sciences

    Populations Served

    Medical students

    Ongoing Project


    Opportunities for Student Involvement


  • Stanford Science Penpals

    Partnering Organization(s)

    Stanford Office of Science Outreach

    Populations Served

    High school students

    Ongoing Project


    Opportunities for Student Involvement



  • Chirag B. Patel, Corinne G. Beinat, Edwin Chang, Sanjiv S. Gambhir, Arutselvan Natarajan. "United States Patent 2021/0199640 A1 (pending) Methods of normalizing aberrant glycolytic metabolism in cancer cells", Leland Stanford Junior University
  • Edwin Chang, Chirag B. Patel, Sanjiv S. Gambhir, Tali Voloshin-Sela, Yaara Porat, Moshe Giladi. "United States Patent 2020/0254242 A1 Using Alternating Electric Fields to Increase Cell Membrane Permeability", Novocure GmbH, Leland Stanford Junior University, Aug 31, 2021

Current Research and Scholarly Interests

My laboratory studies the biology of glioblastoma, the most common and lethal form of primary brain cancer in adults. With the hope of improving outcomes for patients with brain tumors, we investigate new forms of therapy to determine their efficacy in pre-clinical models. We also analyze scans of patients with brain tumors in order to understand imaging features of tumor aggressiveness and response to therapy.

My clinical research focuses on improving delivery of chemotherapy to brain tumors, particularly through the use of alternating electrical fields or tumor treating fields (TTFields).

Clinical Trials

  • Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery Recruiting

    The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery. Panitumumab-IRDye800 can attach to tumor cells and make them more visible using a special camera during surgery, which may help surgeons better distinguish tumor cells from normal brain tissue and identify small tumors that cannot be seen using current imaging methods.

    View full details

  • Study of Tumor Treating Fields With Hypofractionated Chemoradiotherapy in Newly Diagnosed Glioblastoma Recruiting

    The purpose of this study is to determine the safety and efficacy of the combination therapy of TTFields + SRS+ Temozolomide (TMZ) for newly diagnosed glioblastoma (GBM).

    View full details

  • Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) Recruiting

    Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.

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  • [18F]DASA-23 and PET Scan in Evaluating Pyruvate Kinase M2 Expression in Patients With Intracranial Tumors or Recurrent Glioblastoma and Healthy Volunteers Not Recruiting

    This phase I trial studies how well [18F]DASA-23 and positron emission tomography (PET) scan work in evaluating pyruvate kinase M2 (PKM2) expression in patients with intracranial tumors or recurrent glioblastoma and healthy volunteers. PKM2 regulates brain tumor metabolism, a key factor in glioblastoma growth. [18F]DASA-23 is a radioactive substance with the ability to monitor PKM2 activity. A PET scan is a procedure in which a small amount of a radioactive substance, such as [18F]DASA-23, is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the substance is used. Tumor cells usually pick up more of these radioactive substances, allowing them to be found. Giving [18F]DASA-23 with a PET scan may help doctors evaluate PKM2 expression in healthy volunteers and in participants with intracranial tumors or recurrent glioblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mark M. Santos, 650-498-5189.

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  • BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab Not Recruiting

    This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma or glioblastoma) that has come back and have been previously treated with bevacizumab. BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sophie Bertrand, 650-723-4467.

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  • Exablate Blood-Brain Barrier Disruption for the Treatment of rGBM in Subjects Undergoing Carboplatin Monotherapy Not Recruiting

    The purpose of this study is to evaluate the safety and feasibility of the Exablate Model 4000 Type 2 system when used as a tool to open the blood-brain-barrier (BBB) in subjects with recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Hari Priya Yerraballa, MBBS, 650-724-9363.

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  • Hyperpolarized Carbon C 13 Pyruvate Magnetic Resonance Spectroscopic Imaging in Detecting Lactate and Bicarbonate in Participants With Central Nervous System Tumors Not Recruiting

    This early phase I trial studies how well hyperpolarized carbon C 13 pyruvate magnetic resonance imaging works in detecting lactate and bicarbonate in participants with central nervous system tumors. Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Lewis, 650-723-0381.

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  • INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) Not Recruiting

    Phase 1/2 trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab (REGN2810), with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • ONC201 in Adults With Recurrent H3 K27M-mutant Glioma Not Recruiting

    The primary objective of this phase II trial is to determine the efficacy and safety of ONC201, an oral small molecule imipridone DRD2 antagonist, in adult subjects with recurrent high-grade glioma. This study will test the research hypothesis that histone H3 K27M mutation sensitizes to oral administration of ONC201 in gliomas.

    Stanford is currently not accepting patients for this trial.

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  • Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM Not Recruiting

    To test the effectiveness and safety of Optune® given concomitantly with radiation therapy (RT) and temozolomide (TMZ) in newly diagnosed GBM patients, compared to radiation therapy and temozolomide alone. In both arms, Optune® and maintenance temozolomide are continued following radiation therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study of PBI-200 in Subjects With NTRK-Fusion-Positive Solid Tumors Not Recruiting

    This is a first-in-human, open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • TTAC-0001 Phase II Trial With Recurrent Glioblastoma Progressed on Bevacizumab Not Recruiting

    This is a phase II, open-Label clinical trial to evaluate the safety and efficacy of TTAC-0001 in patients with recurrent glioblastoma who was progressed on bevacizumab including therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Hary Priya Yerraballa, 650-724-9363.

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  • Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma Not Recruiting

    This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Plerixafor is a drug that may prevent recurrence of glioblastoma after radiation treatment. Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lawrence Recht, 650-725-8630.

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2023-24 Courses

Graduate and Fellowship Programs

  • Oncology (Fellowship Program)

All Publications

  • Permeabilizing Cell Membranes with Electric Fields CANCERS Aguilar, A. A., Ho, M. C., Chang, E., Carlson, K. W., Natarajan, A., Marciano, T., Bomzon, Z., Patel, C. B. 2021; 13 (9)
  • PTEN mutations predict benefit from tumor treating fields (TTFields) therapy in patients with recurrent glioblastoma. Journal of neuro-oncology Dono, A., Mitra, S., Shah, M., Takayasu, T., Zhu, J. J., Tandon, N., Patel, C. B., Esquenazi, Y., Ballester, L. Y. 2021


    Optimal treatment for recurrent glioblastoma isocitrate dehydrogenase 1 and 2 wild-type (rGBM IDH-WT) is not standardized, resulting in multiple therapeutic approaches. A phase III clinical trial showed that tumor treating fields (TTFields) monotherapy provided comparable survival benefits to physician's chemotherapy choice in rGBM. However, patients did not equally benefit from TTFields, highlighting the importance of identifying predictive biomarkers of TTFields efficacy.A retrospective review of an institutional database with 530 patients with infiltrating gliomas was performed. Patients with IDH-WT rGBM receiving TTFields at first recurrence were included. Tumors were evaluated by next-generation sequencing for mutations in 205 cancer-related genes. Post-progression survival (PPS) was examined using the log-rank test and multivariate Cox-regression analysis.149 rGBM patients were identified of which 29 (19%) were treated with TTFields. No significant difference in median PPS was observed between rGBM patients who received versus did not receive TTFields (13.9 versus 10.9 months, p = 0.068). However, within the TTFields-treated group (n = 29), PPS was improved in PTEN-mutant (n = 14) versus PTEN-WT (n = 15) rGBM, (22.2 versus 11.6 months, p = 0.017). Within the PTEN-mutant group (n = 70, 47%), patients treated with TTFields (n = 14) had longer median PPS (22.2 versus 9.3 months, p = 0.005). No PPS benefit was observed in PTEN-WT patients receiving TTFields (n = 79, 53%).TTFields therapy conferred a significant PPS benefit in PTEN-mutant rGBM. Understanding the molecular mechanisms underpinning the differences in response to TTFields therapy could help elucidate the mechanism of action of TTFields and identify the rGBM patients most likely to benefit from this therapeutic option.

    View details for DOI 10.1007/s11060-021-03755-1

    View details for PubMedID 33881725

  • Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression Neoplasia Patel, C. B., Beinat, C., Xie, Y., Chang, E., Gambhir, S. S. 2021; 23 (1): 58-67
  • Electrophysiological Characterization of Glioma using a Biomimetic Spheroid Model Proceedings of the 10th International IEEE EMBS Conference on Neural Engineering Kim, K. M., Tercan, S., Baday, M., Mahaney, K. B., Recht, L. D., Rajadas, J., Patel, C. B. 2021
  • Recurrent Status Epilepticus in the Setting of Chimeric Antigen Receptor (CAR)-T Cell Therapy The Neurohospitalist Reveron-Thornton, R., Scott, B. J., Post, D., Finley Caulfield, A., Werbaneth, K., Hovsepian, D. A., Spiegel, J., Miklos, D., Thomas, R. P., Patel, C. B. 2021
  • EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial Theranostics Zhou, Q., van den Berg, N. S., Rosenthal, E. L., Iv, M., Zhang, M., Vega Leonel, J. C., Walters, S., Nishio, N., Granucci, M., Raymundo, R., Yi, G., Vogel, H., Cayrol, R., Lee, Y., Lu, G., Hom, M., Kang, W., Hayden Gephart, M., Recht, L. D., Nagpal, S., Thomas, R. P., Patel, C. B., Grant, G. A., Li, G. 2021; 11 (15): 7130-7143

    View details for DOI 10.7150/thno.60582

  • Palliative Care Service Utilization and Advance Care Planning for Adult Glioblastoma Patients: A Systematic Review Cancers Wu, A., Ruiz Colón, G., Aslakson, R., Pollom, E., Patel, C. B. 2021
  • A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2 Induced Glycolytic Reprogramming in Glioblastoma Clinical Cancer Research Beinat, C., Patel, C. B., Haywood, T., Murty, S., Naya, L., Castillo, J., Reyes, S., Phillips, M., Buccino, P., Shen, B., Park, J., Koran, M., Alam, I., James, M., Holley, D., Halbert, K., Gandhi, H., He, J., Granucci, M., Johnson, E., Liu, D., Uchida, N., Sinha, R., Chu, P., Born, D., et al 2021
  • Increasing Diversity in Radiology and Molecular Imaging: Current Challenges. Molecular imaging and biology Fite, B. Z., Hinostroza, V. n., States, L. n., Hicks-Nelson, A. n., Baratto, L. n., Kallianos, K. n., Codari, M. n., Yu, B. n., Jha, P. n., Shams, M. n., Stoyanova, T. n., Chapelin, F. F., Liu, A. n., Rashidi, A. n., Soto, F. n., Quintana, Y. n., Davidzon, G. A., Marycz, K. n., Gibbs, I. C., Chonde, D. B., Patel, C. B., Daldrup-Link, H. E. 2021


    This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9-11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, "racial diversity in STEM," "women in STEM," and "global health," which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare.

    View details for DOI 10.1007/s11307-021-01610-3

    View details for PubMedID 33903986

  • High levels of ubidecarenone (oxidized CoQ10) delivered using a drug-lipid conjugate nanodispersion (BPM31510) differentially affect redox status and growth in malignant glioma versus non-tumor cells. Scientific reports Sun, J., Patel, C. B., Jang, T., Merchant, M., Chen, C., Kazerounian, S., Diers, A. R., Kiebish, M. A., Vishnudas, V. K., Gesta, S., Sarangarajan, R., Narain, N. R., Nagpal, S., Recht, L. 2020; 10 (1): 13899


    Metabolic reprogramming in cancer cells, vs. non-cancer cells, elevates levels of reactive oxygen species (ROS) leading to higher oxidative stress. The elevated ROS levels suggest a vulnerability to excess prooxidant loads leading to selective cell death, a therapeutically exploitable difference. Co-enzyme Q10 (CoQ10) an endogenous mitochondrial resident molecule, plays an important role in mitochondrial redox homeostasis, membrane integrity, and energy production. BPM31510 is a lipid-drug conjugate nanodispersion specifically formulated for delivery of supraphysiological concentrations of ubidecarenone (oxidized CoQ10) to the cell and mitochondria, in both in vitro and in vivo model systems. In this study, we sought to investigate the therapeutic potential of ubidecarenone in the highly treatment-refractory glioblastoma. Rodent (C6) and human (U251) glioma cell lines, and non-tumor human astrocytes (HA) and rodent NIH3T3 fibroblast cell lines were utilized for experiments. Tumor cell lines exhibited a marked increase in sensitivity to ubidecarenone vs. non-tumor cell lines. Further, elevated mitochondrial superoxide production was noted in tumor cells vs. non-tumor cells hours before any changes in proliferation or the cell cycle could be detected. In vitro co-culture experiments show ubidecarenone differentially affecting tumor cells vs. non-tumor cells, resulting in an equilibrated culture. In vivo activity in a highly aggressive orthotopic C6 glioma model demonstrated a greater than 25% long-term survival rate. Based on these findings we conclude that high levels of ubidecarenone delivered using BPM31510 provide an effective therapeutic modality targeting cancer-specific modulation of redox mechanisms for anti-cancer effects.

    View details for DOI 10.1038/s41598-020-70969-0

    View details for PubMedID 32807842

  • Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model Oncoimmunology Murty, S., Haile, S. T., Beinat, C., Aalipour, A., Alam, I. S., Murty, T., Shaffer, T. M., Patel, C. B., Graves, E. E., Mackall, C. L., Gambhir, S. S. 2020; 9 (1)
  • Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. European journal of nuclear medicine and molecular imaging Beinat, C. n., Patel, C. B., Haywood, T. n., Shen, B. n., Naya, L. n., Gandhi, H. n., Holley, D. n., Khalighi, M. n., Iagaru, A. n., Davidzon, G. n., Gambhir, S. S. 2020


    To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies,, NCT03539731 (registered 28 May 2018).

    View details for DOI 10.1007/s00259-020-04687-0

    View details for PubMedID 31938892

  • Visualization of diagnostic and therapeutic targets in glioma with molecular imaging Frontiers in Immunology Li, D., Patel, C. B., Xu, G., Iagaru, A., Zhu, Z., Zhang, L., Cheng, Z. 2020
  • Evaluation of Glycolytic Response to Multiple Classes of Anti-glioblastoma Drugs by Noninvasive Measurement of Pyruvate Kinase M2 Using [18F]DASA-23. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Beinat, C., Patel, C. B., Xie, Y., Gambhir, S. S. 2019


    PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, the key process of tumor metabolism. PKM2 is found in high levels in glioblastoma (GBM) cells with marginal expression within healthy brain tissue, rendering it a key biomarker of GBM metabolic re-programming. Our group has reported the development of a novel radiotracer, 1-((2-fluoro- 6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA- 23), to non-invasively detect PKM2 levels with positron emission tomography (PET).PROCEDURE: U87 human GBM cells were treated with the IC50 concentration of various agents used in the treatment of GBM, including alkylating agents (temozolomide, carmustine, lomustine, procarbazine), inhibitor of topoisomerase I (irinotecan), vascular endothelial and epidermal growth factor receptor inhibitors (cediranib and erlotinib, respectively) anti-metabolite (5-fluorouracil), microtubule inhibitor (vincristine), and metabolic agents (dichloroacetate and IDH1 inhibitor ivosidenib). Following drug exposure for three or 6days (n=6 replicates per condition), the radiotracer uptake of [18F]DASA-23 and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was assessed. Changes in PKM2 protein levels were determined via Western blot and correlated to radiotracer uptake.RESULTS: Significant interactions were found between the treatment agent (n=12 conditions total comprised 11 drugs and vehicle) and the duration of treatment (3- or 6-day exposure to each drug) on the cellular uptake of [18F]DASA-23 (p=0.0001). The greatest change in the cellular uptake of [18F]DASA-23 was found after exposure to alkylating agents (p<0. 0001) followed by irinotecan (p=0. 0012), erlotinib (p=0. 02), and 5-fluorouracil (p=0. 005). Correlation of PKM2 protein levels and [18F]DASA-23 cellular uptake revealed a moderate correlation (r=0.44, p=0.15).CONCLUSIONS: These proof of principle studies emphasize the superiority of [18F]DASA-23 to [18F]FDG in detecting the glycolytic response of GBM to multiple classes of anti-neoplastic drugs in cell culture. A clinical trial evaluating the diagnostic utility of [18F]DASA-23 PET in GBM patients (NCT03539731) is ongoing.

    View details for PubMedID 30989436

  • Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial. ACS nano Arami, H., Patel, C. B., Madsen, S. J., Dickinson, P. J., Davis, R. M., Zeng, Y., Sturges, B. K., Woolard, K. D., Habte, F. G., Akin, D., Sinclair, R., Gambhir, S. S. 2019


    Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

    View details for PubMedID 30714717

  • Positron emission tomography reporter gene strategy for use in the central nervous system PNAS Haywood, T., Beinat, C., Gowrishankar, G., Patel, C. B., Alam, I. S., Murty, S., Gambhir, S. S. 2019

    View details for DOI 10.1073/pnas.1901645116

  • Engineered immune cells as highly sensitive cancer diagnostics. Nature biotechnology Aalipour, A. n., Chuang, H. Y., Murty, S. n., D'Souza, A. L., Park, S. M., Gulati, G. S., Patel, C. B., Beinat, C. n., Simonetta, F. n., Martinić, I. n., Gowrishankar, G. n., Robinson, E. R., Aalipour, E. n., Zhian, Z. n., Gambhir, S. S. 2019


    Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Here, we describe a cell-based in vivo sensor for highly sensitive early cancer detection. We engineer macrophages to produce a synthetic reporter on adopting an M2 tumor-associated metabolic profile by coupling luciferase expression to activation of the arginase-1 promoter. After adoptive transfer in colorectal and breast mouse tumor models, the engineered macrophages migrated to the tumors and activated arginase-1 so that they could be detected by bioluminescence imaging and luciferase measured in the blood. The macrophage sensor detected tumors as small as 25-50 mm3 by blood luciferase measurements, even in the presence of concomitant inflammation, and was more sensitive than clinically used protein and nucleic acid cancer biomarkers. Macrophage sensors also effectively tracked the immunological response in muscle and lung models of inflammation, suggesting the potential utility of this approach in disease states other than cancer.

    View details for PubMedID 30886438

  • The characterization of 18F-hGTS13 for molecular imaging of xC- transporter activity with positron emission tomography. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Beinat, C. n., Gowrishankar, G. n., Shen, B. n., Alam, I. S., Robinson, E. n., Haywood, T. n., Patel, C. B., Azevedo, E. C., Castillo, J. n., Ilovich, O. n., Koglin, N. n., Schmitt-Willich, H. n., Berndt, M. n., Mueller, A. n., Zerna, M. n., Srinivasan, A. n., Gambhir, S. S. 2019


    Purpose: The aim of this study was development of an improved positron emission tomography (PET) radiotracer for measuring xC- activity with increased tumor uptake and reduced uptake in inflammatory cells compared to (S)-4-(3-18F-Fluoropropyl)-L-glutamic acid (18F-FSPG). Experimental design: A racemic glutamate derivative, 18F-hGTS13 was evaluated in cell culture and animal tumor models. 18F-hGTS13 was separated into C5-epimers and the corresponding 18F-hGTS13-isomer1 and 18F-hGTS13-isomer2 evaluated in H460 tumor bearing rats. Preliminary studies investigate the cellular uptake of 18F-hGTS13-isomer2 in multiple immune cell populations and states. Results:18F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor associated radioactivity of 18F-hGTS13 (7.5±0.9%ID/g, n = 3) was significantly higher than with 18F-FSPG (4.6±0.7%ID/g, n = 3, P = 0.01). 18F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3±1.1%ID/g, n-3), and significantly reduced uptake in multiple immune cell populations relative to 18F-FSPG. 18F-hGTS13-isomer2 exhibited increased liver uptake relative to 18F-FSPG (4.6±0.8%ID/g vs. 0.7±0.01%ID/g) limiting its application in hepatocellular carcinoma. Conclusion:18F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC- activity which may provide information regarding tumor oxidation states. 18F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax due to the low background signal in healthy tissue.

    View details for DOI 10.2967/jnumed.119.225870

    View details for PubMedID 31171595

  • 18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study. Journal of neuro-oncology Patel, C. B., Fazzari, E., Chakhoyan, A., Yao, J., Raymond, C., Nguyen, H., Manoukian, J., Nguyen, N., Pope, W., Cloughesy, T. F., Nghiemphu, P. L., Czernin, J., Lai, A., Ellingson, B. M. 2018


    To report the potential value of pre-operative 18F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients.Forty-five patients with a pathological diagnosis of glioma with pre-operative 18F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum 18F-FDOPA SUV in tumor to normal tissue (T/N SUVmax) were measured and used to predict tumor grade, molecular status, and overall survival (OS).A significant correlation was observed between WHO grade and: the volume of contrast enhancement (r = 0.67), volume of T2 hyperintensity (r = 0.42), and 18F-FDOPA uptake (r = 0.60) (P < 0.01 for each correlation). The volume of contrast enhancement and 18F-FDOPA T/N SUVmax were significantly higher in glioblastoma (WHO IV) compared with lower grade gliomas (WHO I-III), as well as for high-grade gliomas (WHO III-IV) compared with low-grade gliomas (WHO I-II). Receiver-operator characteristic (ROC) analyses confirmed the volume of contrast enhancement and 18F-FDOPA T/N SUVmax could each differentiate patient groups. No significant differences in 18F-FDOPA uptake were observed by IDH or MGMT status. Multivariable Cox regression suggested age (HR 1.16, P = 0.0001) and continuous measures of 18F-FDOPA PET T/N SUVmax (HR 4.43, P = 0.016) were significant prognostic factors for OS in WHO I-IV gliomas.Current findings suggest a potential role for the use of pre-operative 18F-FDOPA PET in suspected glioma. Increased 18F-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

    View details for DOI 10.1007/s11060-018-2877-6

    View details for PubMedID 29679199

  • Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET Targeting Human PD-1 Expression. Scientific reports Natarajan, A., Patel, C. B., Habte, F., Gambhir, S. S. 2018; 8 (1): 633


    The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL-2Rγnull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk] and non-blocked [nblk]), for a total of four groups (n = 3-5/group). The xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly increased in the nblk group (7.0 ± 0.5) compared to the blk group (3.4 ± 0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver. In summary, we validated the 64Cu-pembrolizumab tracer's specific hPD-1 receptor targeting and predicted human dosimetry.

    View details for DOI 10.1038/s41598-017-19123-x

    View details for PubMedID 29330552

  • The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Beinat, C. n., Haywood, T. n., Chen, Y. S., Patel, C. B., Alam, I. S., Murty, S. n., Gambhir, S. S. 2018


    There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [18F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer.The cellular uptake of [18F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [18F]FDG. The specificity of [18F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice.[18F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively.Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [18F]DASA-23, for the molecular imaging of prostate cancer with PET. [18F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

    View details for PubMedID 29736561

  • A Novel Engineered Small Protein for Positron Emission Tomography Imaging of Human Programmed Death Ligand-1 : Validation in Mouse Models and Human Cancer Tissues Clinical Cancer Res Natarajan, A., Patel, C. B., Ramakrishnan, S., Panesar, P. S., Long, S. R., Gambhir, S. S. 2018
  • Tumor Treating Fields Increases Membrane Permeability in Glioblastoma Cells Cell Death Discovery Chang, E., Patel, C. B., Pohling, C., Young, C., Song, J., Flores, T., Zeng, Y., Joubert, L. M., Arami, H., Natarajan, A., Sinclair, R., Gambhir, S. S. 2018; 4
  • Southern California neuroinvasive West Nile virus case series. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology Patel, C. B., Trikamji, B. V., Mathisen, G. E., Mishra, S. K. 2017


    Approximately 80% of individuals infected with West Nile virus (WNV) are asymptomatic, and less than 1% suffer from neuroinvasion that can result in permanent neurological deficits or mortality. Our institution's location in southern California predisposes it to a sizable case volume of neuroinvasive WNV. A 2-year retrospective study was performed at the Olive View-UCLA Medical Center to identify patients with confirmed WNV infection with neuroinvasion. Patient demographics, neurological exam findings, and laboratory diagnostics were reviewed. Data were tabulated and are presented as percentage, mean ± standard deviation, or median [range]. Twenty-two patients (36.4% female, age 50.2 ± 10.6 years) were identified between 20 August 2012 and 24 September 2013. The most common positive findings on review of symptoms included fever (81.8%), nausea/vomiting (81.8%), and headache (68.2%). Thirteen patients (59.1%) presented with fever defined as ≥ 37.8 °C. Motor strength was reduced in nine patients (40.9%) and eight patients (36.4%) were hyporeflexive. Lumbar puncture was performed in all but three patients (cerebrospinal fluid [CSF] protein 76.8 ± 29.6 mg/dL and glucose 71.0 ± 18.8 mg/dL). Elevated CSF anti-WNV IgM and IgG antibody was detected in 93.8% and 62.5% of the 16 tested cases, respectively. Elevated serum anti-WNV IgM and IgG antibody was detected in 100% and 72.2% of the 18 tested cases, respectively. Encephalitic presentations, with or without focal neurological deficits (e.g., motor weakness, hypotonia), dominated this series. In endemic areas, seasonal presentation of such symptoms should raise suspicion for WNV with neuroinvasion.

    View details for DOI 10.1007/s10072-017-3164-6

    View details for PubMedID 29119349

  • Movements Here Today, Gone Tomorrow: Images in Clinical Neurology Case of Hyperglycemic Hemichorea. The Neurohospitalist Chang, T. S., Patel, C. B., Keener, A. M., Keselman, I., Jamal, N. I. 2017; 7 (3): 150

    View details for DOI 10.1177/1941874416671648

    View details for PubMedID 28634509

    View details for PubMedCentralID PMC5467814

  • A single demyelinating attack is enough to limit brain growth in children. Neurology Hacohen, Y., Patel, C. B., Hintzen, R. 2017

    View details for DOI 10.1212/WNL.0000000000003894

    View details for PubMedID 28381511

  • Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields. Journal of neuro-oncology Chang, E. n., Pohling, C. n., Beygui, N. n., Patel, C. B., Rosenberg, J. n., Ha, D. H., Gambhir, S. S. 2017


    Glioblastoma (GBM) is the most aggressive and lethal form of brain cancer. Standard therapies are non-specific and often of limited effectiveness; thus, efforts are underway to uncover novel, unorthodox therapies against GBM. In previous studies, we investigated Withaferin A, a steroidal lactone from Ayurvedic medicine that inhibits proliferation in cancers including GBM. Another novel approach, tumor treating fields (TTFields), is thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cells. We hypothesized that combining TTFields with Withaferin A would synergistically inhibit proliferation in glioblastoma. Human glioblastoma cells (GBM2, GBM39, U87-MG) and human breast adenocarcinoma cells (MDA-MB-231) were isolated from primary tumors. The glioma cell lines were genetically engineered to express firefly luciferase. Proliferative potential was assessed either by bioluminescence imaging or cell counting via hemocytometer. TTFields (4 V/cm) significantly inhibited growth of the four cancer cell lines tested (n = 3 experiments per time point, four measurements per sample, p < 0.02 at least; 2-way ANOVA, control vs. treatment). The combination of Withaferin A (10-100 nM) with TTFields significantly inhibited the growth of the glioma cells to a degree beyond that of Withaferin A or TTFields alone. The interaction of the Withaferin A and TTFields on glioma cells was found to be synergistic in nature (p < 0.01, n = 3 experiments). These findings were validated by both bioluminescence and hemocytometric measurements. The combination of Withaferin A with TTFields represents a novel approach to treat GBM in a manner that is likely better than either treatment alone and that is synergistic.

    View details for PubMedID 28681243

  • Multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON): Distinct entity, CAPNON variant, or old neurocysticercosis? Neuropathology : official journal of the Japanese Society of Neuropathology Abdaljaleel, M., Mazumder, R., Patel, C. B., Im, K., Pope, W., Liau, L. M., Vinters, H. V., Yong, W. H. 2016


    We report a case of multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON) with associated multifocal perivascular microcalcifications and vascular calcinosis. Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a very rare condition that may arise in extra-axial and occasionally, in intra-axial locations. Moreover, it is nearly always a solitary mass with only one case with two lesions reported. While the etiology and pathogenesis of CAPNON remains unclear, the histopathology findings of this entity have been well described. We report a case of a 62-year-old woman with 18 calcifying radiologic lesions involving bilateral cerebral hemispheres. Histologically, these lesions have features similar to that reported for CAPNON, including nodular calcification with fibro-osseous components and peripheral histiocytic reaction. The patient had a poorly documented diagnosis of neurocyticercosis 32 years prior, although without tissue confirmation. The lack of detectable cysticercus serum antibody titers, and absence of residual larval or cyst wall tissue render multifocal calcific involution of that parasite unprovable although still plausible. We also raise the possibility of a blood-brain barrier derangement and/or a metabolic disorder as an alternative etiology. Whether this case of MCAPNON shares the same pathogenesis as the usual solitary CAPNON is unclear.

    View details for DOI 10.1111/neup.12349

    View details for PubMedID 27862397

  • Natural Language Processing-Enabled and Conventional Data Capture Methods for Input to Electronic Health Records: A Comparative Usability Study. JMIR medical informatics Kaufman, D. R., Sheehan, B., Stetson, P., Bhatt, A. R., Field, A. I., Patel, C., Maisel, J. M. 2016; 4 (4)


    The process of documentation in electronic health records (EHRs) is known to be time consuming, inefficient, and cumbersome. The use of dictation coupled with manual transcription has become an increasingly common practice. In recent years, natural language processing (NLP)-enabled data capture has become a viable alternative for data entry. It enables the clinician to maintain control of the process and potentially reduce the documentation burden. The question remains how this NLP-enabled workflow will impact EHR usability and whether it can meet the structured data and other EHR requirements while enhancing the user's experience.The objective of this study is evaluate the comparative effectiveness of an NLP-enabled data capture method using dictation and data extraction from transcribed documents (NLP Entry) in terms of documentation time, documentation quality, and usability versus standard EHR keyboard-and-mouse data entry.This formative study investigated the results of using 4 combinations of NLP Entry and Standard Entry methods ("protocols") of EHR data capture. We compared a novel dictation-based protocol using MediSapien NLP (NLP-NLP) for structured data capture against a standard structured data capture protocol (Standard-Standard) as well as 2 novel hybrid protocols (NLP-Standard and Standard-NLP). The 31 participants included neurologists, cardiologists, and nephrologists. Participants generated 4 consultation or admission notes using 4 documentation protocols. We recorded the time on task, documentation quality (using the Physician Documentation Quality Instrument, PDQI-9), and usability of the documentation processes.A total of 118 notes were documented across the 3 subject areas. The NLP-NLP protocol required a median of 5.2 minutes per cardiology note, 7.3 minutes per nephrology note, and 8.5 minutes per neurology note compared with 16.9, 20.7, and 21.2 minutes, respectively, using the Standard-Standard protocol and 13.8, 21.3, and 18.7 minutes using the Standard-NLP protocol (1 of 2 hybrid methods). Using 8 out of 9 characteristics measured by the PDQI-9 instrument, the NLP-NLP protocol received a median quality score sum of 24.5; the Standard-Standard protocol received a median sum of 29; and the Standard-NLP protocol received a median sum of 29.5. The mean total score of the usability measure was 36.7 when the participants used the NLP-NLP protocol compared with 30.3 when they used the Standard-Standard protocol.In this study, the feasibility of an approach to EHR data capture involving the application of NLP to transcribed dictation was demonstrated. This novel dictation-based approach has the potential to reduce the time required for documentation and improve usability while maintaining documentation quality. Future research will evaluate the NLP-based EHR data capture approach in a clinical setting. It is reasonable to assert that EHRs will increasingly use NLP-enabled data entry tools such as MediSapien NLP because they hold promise for enhancing the documentation process and end-user experience.

    View details for PubMedID 27793791

  • MRI Ventral Nerve Root Enhancement in Five Patients Presenting With Extremity Weakness Secondary to Neuroinvasive West Nile Virus. Journal of clinical neuromuscular disease Patel, C. B., Trikamji, B., Mathisen, G., Yim, C., Zipser, B., Mishra, S. 2016; 18 (1): 41-43

    View details for DOI 10.1097/01.cnd.0000496973.95654.fd

    View details for PubMedID 27552389

  • The effects of anesthesia on the morphoproteomic expression of head and neck squamous cell carcinoma: a pilot study TRANSLATIONAL RESEARCH Ferrell, J. K., Cattano, D., Brown, R. E., Patel, C. B., Karni, R. J. 2015; 166 (6): 674-682

    View details for DOI 10.1016/j.trsl.2015.09.001

    View details for Web of Science ID 000366444400013

    View details for PubMedID 26423449

  • Challenges and opportunities for reinvigorating the physician-scientist pipeline JOURNAL OF CLINICAL INVESTIGATION Daye, D., Patel, C. B., Ahn, J., Nguyen, F. T. 2015; 125 (3): 883-887


    Physician-scientists, with in-depth training in both medicine and research, are uniquely poised to address pressing challenges at the forefront of biomedicine. In recent years, a number of organizations have outlined obstacles to maintaining the pipeline of physician-scientists, classifying them as an endangered species. As in-training and early-career physician-scientists across the spectrum of the pipeline, we share here our perspective on the current challenges and available opportunities that might aid our generation in becoming independent physician-scientists. These challenges revolve around the difficulties in recruitment and retention of trainees, the length of training and lack of support at key training transition points, and the rapidly and independently changing worlds of medical and scientific training. In an era of health care reform and an environment of increasingly sparse NIH funding, these challenges are likely to become more pronounced and complex. As stakeholders, we need to coalesce behind core strategic points and regularly assess the impact and progress of our efforts with appropriate metrics. Here, we expand on the challenges that we foresee and offer potential opportunities to ensure a more sustainable physician-scientist workforce.

    View details for DOI 10.1172/JCI80933

    View details for Web of Science ID 000350616500001

    View details for PubMedID 25689260

    View details for PubMedCentralID PMC4362227

  • Predictive Analytics: The Fifth Clinical Element SOUTHERN MEDICAL JOURNAL Peiris, A. N., Patel, C. B. 2013; 106 (4): 290-291

    View details for DOI 10.1097/SMJ.0b013e31828d95f5

    View details for Web of Science ID 000317104700010

    View details for PubMedID 23558420

  • Diffuse large B-cell lymphoma: A metabolic disorder? The American journal of case reports Tanios, G., Aranguren, I. M., Goldstein, J. S., Patel, C. B. 2013; 14: 518-525


    Patient Male, 81 FINAL DIAGNOSIS: Non-Hodgkin lymphoma Symptoms: General weakness • hypoglycemia • metabolic acidosis- Clinical Procedure: - Specialty: Hematology.Challenging differential diagnosis.B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement.We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels.The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

    View details for PubMedID 24349605

    View details for PubMedCentralID PMC3859735

  • Efficacy of 3% saline vs. conivaptan in achieving hyponatremia treatment goals. Methodist DeBakey cardiovascular journal Dominguez, M., Perez, J. A., Patel, C. B. 2013; 9 (1): 49-53


    Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, but its optimal management is still evolving. While guidelines for infusion rates of hypertonic saline (HS) have been introduced, there is a risk of underestimating the response in serum sodium concentration after therapy. Guidelines also have evaluated the use of vasopressin receptor antagonists as alternatives or supplements to standard therapies. This single-center retrospective study from The Methodist Hospital (TMH) compared the effect of HS and conivaptan intervention in the management of 49 patients with hyponatremia from January 2009 through November 2010. Demographics, volume status, medical history, medication data, and serum sodium concentration correction over 48 hours were analyzed. No significant difference was noted with regard to age, ethnicity, gender, volume status, use of medications known to cause hyponatremia, or comorbidities. Baseline serum sodium concentration was not significantly different between HS (120.5 ± 3.8 mEq/L) and conivaptan (118.3 ± 6.7 mEq/L) groups. Regardless of whether the patient was euvolemic or hypervolemic, no significant difference was noted in serum sodium concentration at 4, 12, 24, or 48 hours after initiation of treatment or in frequency of over-correction between groups. This study compares the effect of HS to conivaptan intervention in the management of hyponatremia. No significant differences were identified in adherence to treatment guidelines. Further, based on this small retrospective study, neither agent poses a significant risk of over-correction at 4, 24, or 48 hours of therapy.

    View details for PubMedID 23519387

    View details for PubMedCentralID PMC3600885

  • Toward a Better Understanding of the Retention of Physician-Scientists in the Career Pipeline ACADEMIC MEDICINE Patel, C. B., Schauberger, E. M., Nguyen, F. T. 2012; 87 (4): 390-391

    View details for DOI 10.1097/ACM.0b013e318248c0ad

    View details for Web of Science ID 000302143200006

    View details for PubMedID 22452911

  • Intraoperative conversion to open technique: is informed consent implied? journal of clinical ethics Patel, C. B., Cattano, D. 2012; 23 (1): 60-67


    This case raises issues regarding the anesthesia and surgical components of preoperative informed consent and the differing views of anesthesiologists and surgeons with regards to informed consent, in the context of conversion to open surgery from a minimally invasive approach.

    View details for PubMedID 22462385

  • Xenon exposure in the neonatal rat brain: effects on genes that regulate apoptosis MINERVA ANESTESIOLOGICA Cattano, D., Valleggi, S., Cavazzana, A. O., Patel, C. B., Ma, D., Maze, M., Giunta, F. 2011; 77 (6): 571-578


    In the developing rodent brain, exposure to volatile anesthetics causes widespread neuronal apoptosis in several regions of the brain. Increasing evidence points to a possible neuroprotective role for the anesthetic gas xenon, following neuronal injury. To address this gap in understanding, we explored the transcriptional consequences of xenon in the brains of postnatal day 7 (P7) rats exposed to xenon compared to those of air-breathing animals, with particular emphasis on the mRNA transcript levels of Akt and c-Jun N-terminal kinase kinase 1 (JNKK1), which are important for cell survival and the activation of extrinsic neuroapoptotic pathways, respectively.P7 Sprague/Dawley rats were exposed to air (75% nitrogen, 25% oxygen) or xenon (75% xenon, 25% oxygen) for 120 min (N=6/group). Forebrains were harvested for reverse transcription polymerase chain reaction, which enabled quantification of Akt and JNKK1 mRNA transcripts. Suppression subtractive hybridization was used to explore the "genetic signature" of xenon exposure.Compared to control air-breathing animals, xenon-breathing rats exhibited a 0.7-fold decrease in Akt mRNA expression (P<0.01) and a 1.6-fold increase in JNKK1 mRNA levels (P<0.05).The concomitant decrease in the Akt mRNA expression level and increase in the JNKK1 mRNA transcript level provide evidence that xenon has a neuroapoptotic effect in the developing rodent forebrain. Given these results, further study into the paradoxical neuroprotective and neuroapoptotic effects of xenon is warranted.

    View details for Web of Science ID 000292058300004

    View details for PubMedID 21617619

  • Diagnostic nuclear medicine in the ED AMERICAN JOURNAL OF EMERGENCY MEDICINE Amini, B., Patel, C. B., Lewin, M. R., Kim, T., Fisher, R. E. 2011; 29 (1): 91-101


    Although the decision to use nuclear medicine (NM) modalities in the acute care setting is limited by several factors, there are instances in which the use of NM techniques can provide elegant and efficient solutions to otherwise expensive and resource consuming situations. Herein, we describe the indications and NM techniques used for the evaluation of low-risk patients with chest pain, suspected pulmonary embolus, acute cholecystitis, gastrointestinal bleeding, acute scrotum, and the radiographically occult fracture.

    View details for DOI 10.1016/j.ajem.2009.03.008

    View details for Web of Science ID 000285400500016

    View details for PubMedID 20825918

  • Management of extensive squamous cell carcinoma on the site of radiation-induced dermatitis with severe fibrosis: a case report J Radiother Pract Patel, C. B., Rashid, R. M., Nguyen, T. H. 2010; 9 (2): 125-8
  • Consider using diffusion tensor imaging in Geron phase I trial. AJNR. American journal of neuroradiology Patel, C. B. 2009; 30 (7): E97-?

    View details for DOI 10.3174/ajnr.A1632

    View details for PubMedID 19386734

  • Letter by Patel Regarding Article, "A Primer in Longitudinal Data Analysis" CIRCULATION Patel, C. B. 2009; 120 (4): E25-E25
  • Effect of VEGF Treatment on the Blood-Spinal Cord Barrier Permeability in Experimental Spinal Cord Injury: Dynamic Contrast-Enhanced Magnetic Resonance Imaging JOURNAL OF NEUROTRAUMA Patel, C. B., Cohen, D. M., Ahobila-Vajjula, P., Sundberg, L. M., Chacko, T., Narayana, P. A. 2009; 26 (7): 1005-1016


    Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

    View details for DOI 10.1089/neu.2008.0860

    View details for Web of Science ID 000267965500006

    View details for PubMedID 19226205

  • Blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced MRI NMR IN BIOMEDICINE Cohen, D. M., Patel, C. B., Ahobila-Vajjula, P., Sundberg, L. M., Chacko, T., Liu, S., Narayana, P. A. 2009; 22 (3): 332-341


    After a primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies were performed up to 56 days after SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI (non-enhancing tissue). DCE-MRI data were analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. However, on the basis of DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days after SCI. In addition, open-field locomotion was evaluated using the 21-point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed.

    View details for DOI 10.1002/nbm.1343

    View details for Web of Science ID 000264578200012

    View details for PubMedID 19023867

  • The effect of dental artifacts, contrast media, and experience on Interobserver contouring variations in head and neck anatomy 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology O'Daniel, J. C., Rosenthal, D. I., Garden, A. S., Barker, J. L., Ahamad, A., Ang, K. K., Asper, J. A., Blanco, A. I., De Crevoisier, R., Holsinger, C., Patel, C. B., Schwartz, D. L., Wang, H., Dong, L. LIPPINCOTT WILLIAMS & WILKINS. 2007: 191–98


    To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience.Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed.In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD < or =3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary).Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

    View details for DOI 10.1097/01.coc.0000256704.58956.45

    View details for Web of Science ID 000245637100014

    View details for PubMedID 17414470

  • Cultural humility in medicine: beyond the K-20 pipeline. Texas medicine Patel, C. B. 2006; 102 (4): 7-?

    View details for PubMedID 17128753

  • Sinusoidal modeling of ictal activity along a thalamus-to-cortex seizure pathway I: New coherence approaches ANNALS OF BIOMEDICAL ENGINEERING Sherman, D. L., Patel, C. B., Zhang, N., Rossell, L. A., Tsai, Y. C., Thakor, N. V., Mirski, M. A. 2004; 32 (9): 1252-1264


    Understanding associations in neuronal circuitry is critical for tracing epilepsy pathways. Two new methods of measuring coherence between field potentials and EEG channels are proposed for modeling the level of linear association between channels during epileptic seizures. These methods rely upon modeling the repetitive clonic seizure activity as a sum of sinusoids with varying degrees of phase locking. Estimating the amplitude of sinusoids from correlation and cross-correlation time domain data, we can find the coherences from a ratio of these amplitudes. One method utilizes amplitude finding from the multiple signal classification (MUSIC) technique. The other method uses alterations in amplitude of individual sinusoids and their ratios in a matrix pencil equation formed from cross- and auto-correlation matrices. The corresponding generalized eigenvalues of these equations form the coherence ratios. This utilizes the estimation of signal parameters using rotational invariance techniques (ESPRIT) algorithm to arrive at coherence amplitude ratios. Simulations illustrate that the MUSIC method provides better noise immunity as it out-performs the conventional Fourier transform-based method for coherence estimation. Both coherence estimators reflect presence of sinusoidal components that are propagated or not propagated along a particular transmission pathway. We illustrate the value of both methods by examining the strength of correlation between seizure EEG from specific thalamic nuclei and cortex in a rodent model of generalized epilepsy. The pentylenetetrazol (PTZ) chemoconvulsant model in rats reflects selective activation of the anterior thalamic nucleus. Using both methods, this neuronal element has much larger coherence with cortex than another thalamic region, the posterior thalamus (p < 0.05). These methods isolate the unique contribution of anterior thalamus in the formation of an ictal network and corroborate earlier conventional or periodogram techniques.

    View details for Web of Science ID 000223549700008

    View details for PubMedID 15493512

  • Prediction of PTZ-induced seizures using wavelet-based residual entropy of cortical and subcortical field potentials IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Paul, J. S., Patel, C. B., Al-Nashash, H., Zhang, N., Ziai, W. C., Mirski, M. A., Sherman, D. L. 2003; 50 (5): 640-648


    Our proposed algorithm for seizure prediction is based on the principle that seizure build-up is always preceded by constantly changing bursting levels. We use a novel measure of residual subband wavelet entropy (RSWE) to directly estimate the entropy of bursts, which is otherwise obscured by the ongoing background activity. Our results are obtained using a slow infusion anesthetized pentylenetetrazol (PTZ) rat model in which we record field potentials (FPs) from frontal cortex and two thalamic areas (anterior and posterior nuclei). In each frequency band, except for the theta-delta frequency bands, we observed a significant build-up of RSWE from the preictal period to the first ictal event (p < or = 0.05) in cortex. Significant differences were observed between cortical and thalamic RSWE (p < or = 0.05) subsequent to seizure development. A key observation is the twofold increase in mean cortical RSWE from the preictal to interictal period. Exploiting this increase, we develop a slope change detector to discern early acceleration of entropy and predict the approaching seizure. We use multiple observations through sequential detection of slope changes to enhance the sensitivity of our prediction. Using the proposed method applied to a cohort of four rats subjected to PTZ infusion, we were able to predict the first seizure episode 28 min prior to its occurrence.

    View details for DOI 10.1109/TBME.2003.810683

    View details for Web of Science ID 000182870900012

    View details for PubMedID 12769440

  • Residual entropy reveals effects of deep brain stimulation on neural activity in PTZ-induced epilepsy Patel, C. B., Sherman, D. L., Paul, J. S., Zhang, N., Mirski, M. A. 2003: 2281–84
  • Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation CANCER RESEARCH Loeb, D. M., Evron, E., Patel, C. B., Sharma, P. M., Niranjan, B., Buluwela, L., Weitzman, S. A., Korz, D., Sukumar, S. 2001; 61 (3): 921-925


    We analyzed Wilms' tumor suppressor 1 (WT1) expression and its regulation by promoter methylation in a panel of normal breast epithelial samples and primary carcinomas. Contrary to previous reports, WT1 protein was strongly expressed in primary carcinomas (27 of 31 tumors) but not in normal breast epithelium (1 of 20 samples). Additionally, the WT1 promoter was methylated in 6 of 19 (32%) primary tumors, which nevertheless expressed WT1. The promoter is not methylated in normal epithelium. Thus, although tumor-specific methylation of WT1 is established in primary breast cancer at a low frequency, other transcriptional regulatory mechanisms appear to supercede its effects in these tumors. Our results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not have a tumor suppressor role in breast cancer.

    View details for Web of Science ID 000167020100027

    View details for PubMedID 11221883