Projects Supported by the Center

 

 

 

Current Collaborative Projects

  1. Metabolic Imaging Comparisons of Patient-derived Models of Renal Cell Carcinoma (PI: Donna Peehl, PhD)
    Project Goal: The proposed research is relevant to public health because predictive preclinical models are needed to reduce death from renal cell carcinoma (kidney cancer), which kills almost 15,000 Americans each year. The research is relevant to the mission of the NIH, and the NCI, because it will provide information about dysregulated metabolism in kidney cancer and how metabolism might be targeted to improve detection and treatment of kidney cancer to reduce mortality.
  2. Non-invasive Assessment of Renal Tumors and Diabetic Nephropathy (PI: Zhen Jane Wang, MD) 
    Project Goal: The goal of this work is to a) assess renal tumor metabolic profile using hyperpolarized 13C MR using a multi-probe approach, pyruvate, bicarbonate, urea, and dehydroascorbate (DHA), as a mean to differentiate benign/indolent from aggressive renal tumors, and to assess early treatment response; and b) will develop hyperpolarized 13C MR methods to interrogate key metabolic changes underlie diabetic nephropathy, namely altered oxidative stress (via 13C DHA) and glycolytic metabolism (via 13C fructose). 
  3. MR Metabolic Imaging of Targeted Therapies & Metabolic Reprogramming in Brain Tumors (PI: Sabrina Ronen, PhD) 
    Project Goal: This research aims to better characterize brain tumors and to address the currently unmet need for non-invasive imaging methods to monitor the effect of PI3K/AKT/mTOR inhibitors. This will inform on drug delivery and molecular response, and will enable longitudinal monitoring of drug action at the tumor site. It will provide a tool to help optimize therapeutic regimens that are specifically tailored to the tumor and ultimately could result in more personalized care for GBM patients enhancing quality of life and outcome. In the long term the same approach could be implemented in other types of cancer that are driven by PI3K/AKT/mTOR signaling.
  4. Novel Hyperpolarized 13C Molecular Imaging Techniques for Differentiating NAFLD and NASH (PI: Michael Ohliger MD, PhD, Cornelius von Morze, PhD)
    Project Goal: The goal of this project is to investigate the new application of hyperpolarized 13C MRI technology to the assessment of non-alcoholic fatty liver disease (NAFLD). By addressing important limitations of the “gold standard” method of liver biopsy (particularly invasiveness), this project addresses an important unmet clinical need and therefore has the potential to make a significant impact on the clinical management of liver disease.
  5. Hyperpolarized C-13 MR Pulse Sequence Developments for Novel Contrast (PI: Peder Larson, PhD)
    Project Goal: This project will develop and test new HP C-13 metabolite diffusion MRI methods to non-invasively measure metabolism and cellular transport. Both of these mechanisms are highly implicated in aggressive types of cancer, as well as other diseases such as kidney failure and non-alcoholic fatty liver disease. This method has significant potential to improve healthcare by better characterizing disease severity and improving outcome predictions following treatment.
  6. Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring (PI: Rahul Aggarwal, MD)
    Project Goal: The successful outcome of this image-guided drug delivery proposal will result in the clinical translation of a quantitative multi-probe HP 13C MR metabolic imaging approach that can guide, monitor, and evaluate drug delivery and response for the treatment of neuroendocrine prostate cancer to enable new clinical trials and provide individualized patient care. While this project initially focuses on advanced prostate cancer, these new metabolic imaging techniques could ultimately benefit the clinical management of other cancers and diseases.
  7. MR Metabolic Imaging of Multiple Sclerosis with HP C13 MR (PI: Myriam Chaumeil, PhD) 
    Project Goal: The proposed research will validate new metabolic imaging approaches allowing for improved non-invasive assessment of neuroinflammatory processes in Multiple Sclerosis (MS). Upon clinical translation, the methods developed in this proposal will serve to ameliorate clinical management of MS patients, help refine therapeutic regimens and, ultimately, lead to better outcome and patient quality of life.
  8. Translating HP 13C MRI for Assessing Drug Target Inhibition in Phase 1 Trials (PI: Pamela Munster, MD)
    Project Goal: The goal of this academic-industrial collaborative research project is to accomplish the clinical translation of the “next-generation imaging technology” hyperpolarized C13 MRI to address the unmet clinical need of quantifying metabolic response to targeted therapy (e.g. mTOR pathway inhibitors) non-invasively in patients with advanced malignancies. 
  9. Imaging and Tissue Correlates to Optimize Management of Glioblastoma (PI: Susan Chang, MD)
    Project Goal: The purpose of this P01 project is to develop and test novel MR metabolic imaging approaches that will help to distinguish recurrent tumor from normal brain and treatment effects in patients with glioblastoma (GBM). The prognosis for patients with these high grade lesions is relatively poor and identifying more effective treatments is a priority for the neuro-oncology community. Our hypothesis is that integrating multi-parametric MR imaging with novel H-1 MR spectroscopic imaging techniques and new hyperpolarized C-13 metabolic imaging methods will provide a better definition of tumor burden and will help to resolve the ambiguities inherent in conventional imaging.
  10. Developing Specialized Prostate Cancer HP MRI Techniques to Improve Clinical Management (PI: Robert Bok, MD, PhD, Jeremy Gordon, PhD)
    Project Goal: The goal of this project is to develop new HP MRI techniques to improve the clinical management of prostate cancer including the detection of aggressive cancer in active surveillance patients.

 

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Active Grants Awarded & Supported by the Center

  1. Monitoring metabolism in GBM using hyperpolarized C-13 imaging and H-1 MRSI (PI: Janine Lupo, PhD) [NIH P50 CA097257; 09/20/02-08/31/23] 
    Project Goal: The purpose of this project is to develop non-invasive markers for assessing tumor aggressiveness and monitoring response to therapy for patients with gliobastoma by integrating two Magnetic Resonance (MR) metabolic imaging strategies with conventional anatomic imaging. The first method is H-1 MR spectroscopic imaging, which provides steady state metrics that describe tumor burden and predict overall survival. The second method is hyperpolarized C-13 imaging, which is a novel technology for monitoring dynamic changes in the magnitude and rate of conversion of pyruvate to its metabolic products. We will use the information obtained to differentiate normal brain, tumor and treatment related effects in order to improve the clinical evaluation of patients with GBM. 
  2. Metabolic Imaging of Brain Tumor Response to Therapy (PI: Sabrina Ronen, PhD) [NIH R01 CA197254; 04/01/16-03/31/22] 
    Project Goal: The proposed research will identify and validate new magnetic resonance metabolic imaging approaches that will enhance current imaging methods and help predict oligodendroglioma and astrocytoma response to therapy in a personalized way.  This approach will serve to improve noninvasive, precision-medicine imaging of response to current and emerging therapies, resulting in improved care for oligodendroglioma and astrocytoma patients. 
  3. Metabolic Reprogramming in Brain Tumors (PI: Sabrina Ronen, PhD) [NIH R01 CA172845; 02/05/13-2/28/23]
    Project Goal: The proposed research builds on our previous findings and aims to identify and validate noninvasive magnetic resonance spectroscopy-based metabolic imaging biomarkers of response to emerging therapies that target mutant IDH1 gliomas and that are currently in clinical trials. As such, our study would improve patient care resulting in personalized precision care that will enhance the quality of life and potential outcome of mutant IDH1 glioma patients.
  4. Non Invasive Characterization of Oligodendroglioma (PI’s: Susan Chang, MD; Dan Vigneron, PhD; Sabrina Ronen, PhD) [NICO; 09/01/16-08/31/21]
    Project Goal: The goal of the proposed study is to develop and implement novel imaging methods to enhance the early detection of recurrence for these patients and facilitate implementation of new treatment strategies. 
  5. Precision Therapy for Neonatal Brain Injury (PI: Donna Ferriero, MD, MS) [NIH R35 NS097299; 12/01/16-11/30/24] 
    Project Goal: Lack of oxygen to the newborn brain is the major cause of lifelong disability in children resulting in mental retardation, epilepsy and cerebral palsy. Understanding pathways for protecting the brain will result in therapeutic avenues for brain recovery.
  6. Clinical Translation of Hyperpolarized 13C-Urea for Cancer MR Molecular Imaging (PI’s: John Kurhanewicz PhD & Dan Vigneron, PhD) [NIH R01 CA214554; 03/06/17-02/28/22] 
    Project Goal: The successful outcome of this Academic Industrial Partnership proposal will result in the development and translation into the clinical setting of new tools and methods to enable greatly improved perfusion and metabolic MR imaging of human cancer.  While this project initially focuses on prostate cancer, these new molecular imaging techniques could ultimately benefit the clinical management of other cancers and diseases. 
  7. Multi-Site Development & Evaluation of a Quantitative 3D Hyperpolarized C-13 MRI Clinical Prostate Cancer Exam (PI: James Bankson, PhD & Subcontract PI: Dan Vigneron, PhD) [NIH R01 CA211150; 03/01/17-02/28/22]
    Project Goal: This multi-site, multidisciplinary project at MD Anderson Cancer Center UT Houston and UCSF is to develop a new prostate imaging protocol and translate it for novel patient studies at both institutions.
  8. Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring (PI: Rahul Aggarwal, MD & John Kurhanewicz, PhD) [NIH R01 CA215694; 06/1/17-5/31/22] 
    Project Goal: This application seeks to use a combination of HP 13C glutamine and 13C pyruvate to non-invasively distinguish between adenocarcinoma and neuroendocrine prostate cancer (NEPC) and monitor its response to therapy in patients with metastatic castrate resistant prostate cancer.
  9. MR Metabolic Imaging of Multiple Sclerosis (PI: Myriam Chaumeil, PhD) [NIH R01 NS102156; 07/01/17-06/30/22]
    Project Goal: To test the hypothesis that HP MR metabolic imaging can detect neuroinflammatory processes in Multiple Sclerosis and improve monitoring of progression and therapeutic response. 
  10. Metabolic Imaging Comparisons of Patient-derived Models of Cell Carcinoma (PI: Donna Peehl, PhD & John Kurhanewicz, PhD) [U01 CA217456; 09/01/17-07/31/22]
    Project Goal: The goal of this application is to use non-invasive magnetic resonance-based imaging techniques including HP C-13 MRI to compare the metabolic profiles of four types of patient-derived models (PDMs) of renal cell carcinoma (RCC): patient-derived xenografts (PDXs), tissue slice cultures (TSCs), primary cell cultures, and xenografts generated from cell cultures.
  11. Novel Hyperpolarized 13C Molecular Imaging Techniques for Differentiating NAFLD and NASH (PI’s: Michael Ohliger, MD, PhD & Cornelius von Morze, PhD) [NIH R01 DK115987; 09/20/18-08/31/23] 
    Project Goal: The goal of this project is to investigate the new application of hyperpolarized 13C MRI technology to the assessment of non-alcoholic fatty liver disease (NAFLD). By addressing important limitations of the “gold standard” method of liver biopsy (particularly invasiveness), this project addresses an important unmet clinical need and therefore has the potential to make a significant impact on the clinical management of liver disease. 
  12. Application of Hyperpolarized 13C Interstitial pH Imaging to Risk Stratification in Prostate Cancer (PI: Robert Flavell, MD , PhD) [NIH R21 EB026012; 05/01/18-01/31/22] 
    Project Goal: In this proposal, we describe a method for predicting the presence of aggressive prostate cancer and subsequent disease progression using a recently developed method for high signal to noise ratio hyperpolarized 13C imaging of interstitial pH using 13C bicarbonate produced by polarization of a precursor molecule, glycerol carbonate. A plan for optimization of the technique and suitable quality control measures are proposed for subsequent FDA IND submission. This method could be incorporated in prostate magnetic resonance imaging protocols and could find immediate use in initial staging of prostate cancer.
  13. American Cancer Society Imaging Metabolism and Cellular Transport in Cancer (PI: Peder Larson, PhD) [RSG-18-005-01 CCE; 07/01/18-06/30/22]
    Project Goal: The goal of this project is to translate our novel lactate production and efflux imaging method into clinical studies to improve distinction of low grade from high grade disease.  Specific aims: 1. Clinical prostate cancer studies with new imaging method to identify aggressive disease 2. Clinical renal cancer studies with new imaging method to identify aggressive disease 3. Multi-agent methods for measurements of multiple metabolic and transport pathways.
  14. Hyperpolarized C-13 MRI for Early Detection of Aggressive Prostate in Active Surveillance Patients (PI’s: Robert Bok, MD, PhD & Dan Vigneron, PhD) [NIH U01 CA232320; 04/11/19-03/31/24]
    Project Goal: The goal of this prostate imaging project is to investigate the addition of a new safe, non-radioactive 5-minute hyperpolarized 13C-pyruvate MR scan to a clinical mpMRI exam in order to create a metabolic imaging solution for the unmet clinical need for the detection of aggressive cancer in the prostate in patients prior to and enrolled in “Active Surveillance”. Success of this project would improve the detection of aggressive cancer missed by biopsy sampling error enabling earlier treatment decisions or increased confidence in selecting Active Surveillance for more patients; thus reducing overtreatment. 
  15. Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods (PI’s: Jeremy Gordon, PhD & Dan Vigneron, PhD) [NIH U01 EB026412; 06/01/19-02/29/24] 
    Project Goal: The goal of this Bioengineering Research Partnership project (with partners/collaborators at Stanford, MD Anderson, UCB, UFlorida, GE & Isotec) is to develop new techniques and test them through early-phase studies in primary and metastatic prostate cancer to create the most reliable, cost-effective, high quality HP C-13 MRI exams possible to benefit individual patients and future clinical trials. While this project focuses on prostate cancer, these bioengineering developments are designed to be generally applicable to human HP MRI studies benefiting a broad variety of studies
  16. Application of Hyperpolarized 13C Magnetic Resonance Imaging to Detect Target Inhibition of NF-kB Activation and Response in Primary CNS Lymphoma (PI’s: James Rubenstein, MD & Myriam Chaumeil, PhD) [NIH R01 CA239462; 07/04/19-06/30/24]
    Project Goal: Primary CNS Lymphoma is an aggressive form of activated-B-cell type large cell lymphoma, an important cause of cancer-related death worldwide. Activated B-cell lymphomas are driven by NF-kB, a key pro-survival pathway. We are implementing an innovative metabolic imaging approach, HP 13C MRI, to dissect the pathogenesis of NF-kB in primary CNS lymphoma: to identify novel and more effective combinations of NF-kB targeting agents and to identify novel biomarkers that may predict resistance to immunotherapy. We will also perform the first clinical trial of HP 13C MR in primary CNS lymphoma patients to evaluate its potential to facilitate diagnosis, prognostication, and ultimately precision medicine.
  17. Non-invasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma (PI’s: Susan Chang, MD & Dan Vigneron, PhD) [NIH P01 CA118816; 07/01/07-07/31/24] 
    Project Goal: The objective of the proposed program project grant is to improve the management of patients with different molecular subgroups of glioma defined by their 1p19q co-deletion, IDH mutation, and TERT promotor mutation status. This will be achieved by identifying multi-parametric imaging markers that are specific to each sub-type, elucidating mechanisms that influence the regulation of mutant TERT promotor in subgroups with divergent molecular and clinical features, defining metabolic signatures of TERT expression, and implementing novel 1H and 13C metabolic imaging strategies for monitoring individual patients during the course of their disease.
  18. Hyperpolarized 13C Pyruvate MRI for Early Response Assessment in Pancreatic Ductal Adenocarcinoma (PI: Jane Wang, MD) [UCSF RAP Grant; 07/01/19-12/31/20] 
    Project Goal: The objective of this pilot study is to demonstrate the application of hyperpolarized (HP) 13C pyruvate magnetic resonance imaging (MRI) as an innovative tool for early response assessment in pancreatic ductal adenocarcinoma (PDA).
  19. Clinical Translation of Hyperpolarized 13C Interstitial pH Imaging for Better Risk Stratification of Prostate Cancer (PI: Robert Flavell, MD, PhD) [DOD US Army Med. Res Acq. Activity W81XWH1910866; 09/30/19-09/29/22]
    Project Goal: The goal of this application is to translate this promising method for the detection of clinically significant prostate cancer. We have recently developed an imaging method based on the use of hyperpolarized 13C magnetic resonance imaging using a nontoxic sodium bicarbonate (BiC) agent. This method, HP pH MRI, can image tissue interstitial pH with high resolution and can be readily incorporated into a multiparametric prostate MRI.
  20. Exosome Enhanced Immunotherapy & Imaging of Prostate Cancer Response with Hyperpolarized 13C-MRI (PIs: Robert Bok, MD, PhD & Robert Blelloch, MD, PhD)
  21. Upgrade of an Obsolete 3.35T DNP Polarizer to Enable New HP C-13 Technology Development (PI: Dan Vigneron, PhD) [NIH S10 OD025077; 04/15/20-04/14/22] 
    Project Goal: The requested upgrade of an obsolete 3.35T prototype GE DNP Polarizer to a new “state-of-the-art” Next-Generation 5T SPINlab-QC with improved performance aims to significantly benefit 15 NIH funded projects enabling unprecedented translation studies of new agents beyond 13C-pyruvate. This instrument would be supported by, and sited in, the NIH-funded Hyperpolarized MRI Technology Resource Center with strong institutional support. The upgraded instrument will also benefit the center’s training and dissemination activities.
  22. Imaging Telomere Maintenance Mechanisms in Gliomas (PI: Pavithra Viswanath, PhD & Sabrina Ronen, PhD) [NIH R01 CA239288;  02/11/20-01/31/25]
    Project Goal: Telomere maintenance mechanisms (TMMs) are molecular hallmarks of cancer and are linked to significant metabolic reprogramming in brain tumors. Our goal is to leverage this link to identify novel, translational, metabolic imaging biomarkers that can non-invasively inform on TMM status and, thereby, provide a means of distinguishing tumor from normal brain, edema or necrosis, of monitoring tumor recurrence, of tracking response to therapy including novel TMM inhibitors and of monitoring the development of resistance to TMM inhibitors. This research will, therefore, have the potential to significantly enhance quality of life and care for brain tumor patients.
  23. Co-Clinical Quantitative Imaging of Small Cell Neuroendocrine Prostate Cancer Using Hyperpolarized 13C MRI (PI: Renuka Sriram, PhD & John Kurhanewicz, PhD & Donna Peehl, PhD) [NIH/NCI U24 CA253377; 09/07/20-08/31/25] 
    Project Goal: The goal of this Oncology Co-Clinical Imaging Research Program (CIRP) proposal is to overcome the translational barrier, as stated in PAR-18-184, to develop co-clinical imaging research resources that will encourage a consensus on how quantitative imaging methods are optimized to improve the quality of imaging results for co-clinical trials.
  24. Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring (PI: Dan Vigneron, PhD & Rahul Aggarwal, MD) [NIH/NCI R01 CA256740; 12/01/20-11/30/25] 
    Project Goal: The goal of this project is to investigate a new molecular imaging approach for novel measurements of drug target inhibition in an early-phase feasibility clinical trial in prostate cancer patients with bone metastases. While this early stage feasibility trial focuses on prostate cancer, these methods are designed to be applicable to other metastatic cancer MRI studies and in general to other cancer investigations.
  25. Translating Hyperpolarized 13C Metabolic MRI to Predict Renal Tumor Aggressiveness (PI: Jane Wang, MD & Peder Larson, PhD) [NIH R01 CA249909; 01/01/21-12/31/25] 
    Project Goal: There has been a significant increase in incidentally discovered localized renal tumors, and it remains a challenge to reliably and noninvasively differentiate benign tumors from renal cancers or differentiate low grade from high grade renal cancers. In this study, we will apply a powerful imaging technology, hyperpolarized 13C metabolic MRI, to renal tumors for the first time to address an unmet need for noninvasive predictors of tumor aggressiveness. Successful completion of this work will aid in future management of patients with renal tumors by reducing the current overdiagnosis and treatment of indolent tumors while enabling early detection of aggressive renal cancers that require timely surgery. 
  26. High Field MRI for Optimized Translational 1H Multiparametric and Multinuclear Imaging Research (PI: John Kurhanewicz, PhD) [NIH S10 OD030256; 04/01/21-03/31/22] 
    Project Goal: The proposed replacement of a unique but aging, commercially unsupported, mouse only vertical bore Varian 14T pre-clinical MRI to a state-of-the-art Bruker 9.4T horizontal bore MRI scanner large enough for mice and rats is justified by the research needs of 24 currently funded projects (20 NIH grants) in translational and clinical biomedical research. The UCSF RRP Pre-Clinical Imaging Core, where the 9.4T MRI will be sited, provides advanced pre-clinical imaging instrumentation consisting of 4 scanners, 2 DNP polarizers, other supporting small equipment, wet lab facilities, as well as expert personnel for translational pre-clinical imaging research for the entire UCSF campus. Specifically, the Pre-clinical Imaging Core serves a broad research and clinical community (50+ Principal Investigators in the Schools of Medicine and Pharmacy) and supports a broad spectrum of basic and clinical research (oncology, diabetes, cardiac disease, brain disorders, liver disease, infectious diseases and drug discovery).
  27. Hyperpolarized C-13 MRI Techniques to Monitor Radiation Therapy Response in Prostate Cancer Patients (PIs: Dan Vigneron, PhD & Robert Bok, MD, PhD) [NIH R01 CA238379; 07/01/21-6/30/06] 
    Project Goal: The goal of this project is to develop new techniques and apply an innovative MR molecular imaging approach to monitor HP pyruvate metabolism in prostate cancer patients pre- and post-radiation therapy for the first time. While this early stage biomarker-driven trial focuses on prostate cancer, these methods are designed to be applicable to other prostate cancer HP MRI studies and in general to other cancer investigations.
  28. Hyperpolarized 13C Metabolic MRI for Noninvasive Monitoring of Kidney Injury (PIs: Peder Larson, PhD & Jane Wang, MD) [NIH R21 DK130002; 07/12/21-04/30/23] 
    Project Goal: We will develop a novel kidney metabolic imaging tool based on the emerging hyperpolarized 13C magnetic resonance imaging modality to non-invasively investigate kidney energy metabolism as a biomarker of kidney injury. This project includes technology development of innovative image acquisition and data analysis strategies that will be evaluated in human subject studies. This tool has an outstanding potential to advance our understanding of energy metabolism in kidney disease, a major public health problem in the United States, and to improve its timely diagnosis and therapy monitoring for both clinical research and clinical care.
  29. Monitoring Patients with IDH-Mutant Astrocytoma Using Dynamic And Steady-State Metabolic Imaging (PI: Yan Li, PhD) [DoD W81XWH-21-1-0412; 09/01/21-08/31/24] 
    Project Goal: To evaluate steady state and dynamic metabolic biomarkers in managing patients with IDH+ astrocytoma by integrating 3D 1H MRSI with novel HP [1-13C]pyruvate metabolic imaging methodologies. The hypothesis being tested is that integrating these two metabolic imaging into MR scans of patients with IDH+ astrocytoma will make it possible to differentiate between normal brain, tumor and treatment related effects.
  30. Dynamic Metabolic Assessment of the Healthy Brain (PI: Duan Xu, PhD) [UCSF RAP; 07/01/21-06/30/22] 
    Project Goal: This project is designed to leverage advances in dynamic metabolic imaging methods to allow assessments of real-time metabolic function in the human brain.
  31. Metabolic Characterization and Detection of Targeted Therapeutic Response of PSMA-negative Transdifferentiated Advanced Prostate Cancer with Hyperpolarized 13C MRI (PI: Renuka Sriram, PhD) [Benioff Initiative for Prostate Cancer Research Grant, 07/01/21-06/30/24] 
    Project Goal: This project proposes that HP 13C-pyruvate MRI can monitor response of mCRPC tumors to BETi in conjunction with enzalutamide treatment using liver and bone PDX mCRPC models and imaging protocols that parallel ongoing clinical trials of mCRPC patients.

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Completed Grants Supported by the Center

  1. Hyperpolarized C-13 MR Pulse Sequence Developments for Novel Contrast (PI: Peder Larson, PhD) [NIH R00 EB012064; 09/01/11-08/31/15] 
  2. Project Goal: The goal of this mentored career development award is to create new preclinical MR imaging methods tailored for hyperpolarized substrates that provide improved metabolism and perfusion contrast in vivo
  3. PET and MR-Compatible Bioreactor for Cross-Platform Biomarkers Development (PIs: Henry VanBrocklin, PhD & John Kurhanewicz, PhD) [NIH R21 CA171766; 08/01/12-07/31/15] 
    Project Goal: The goal of this research is to optimize a 5mm MR-compatible PET 3D cell/tissue culture bioreactor and test it by using a combination of hyperpolarized (HP) 13C MR and PET probes.
  4. MR Imaging of IDH Mutational Status in Brain Tumors (PI: Sabrina Ronen, PhD) [NIH/NCI R21 CA161545; 04/02/12-03/31/15] 
    Project Goal: The goal of this project is to develop magnetic resonance spectroscopy (MRS)-based approaches for non-invasive assessment of the mutational status and activity of isocitrate dehydrogenase (IDH) by detecting the conversion of hyperpolarized aKG into 2-HG.
  5. DNP Polarization Agents for Real-Time Metabolic Imaging and Clinical Diagnosis (PI: Joseph Walish, PhD & Subcontract PI: John Kurhanewicz, PhD) [NIH STTR – R41 CA192567; 12/14/14-11/30/15] 
  6. Project Goal: In this Phase I effort we propose the application of our 1,3-bisdiphenylene-2-phenylallyl (BDPA) radical technology for the production of tunable polarization agents to expand the applicability of hyperpolarized 13C MR. If successful these proposed radicals and methods will generate immediate sales for our start-up company (DyNuPol) and allow lower cost radicals for improved hyperpolarized MR preparations of both existing and new hyperpolarized probes, ultimately allowing a wider range of hyperpolarized probes to be investigated for use in the medical imaging community.
  7. MR Metabolic Imaging of Response to Targeted Therapies in GBM (PI: Sabrina Ronen, PhD) [NIH/NCI R01 CA154915; 09/08/11-06/30/16] 
    Project Goal: The goal of the proposed research is to develop and mechanistically validate MR-detectable metabolic biomarkers in order to evaluate the molecular response of glioblastoma multiforme (GBM) to novel therapies that target oncogenic signaling pathways, which are activated within such lesions.
  8. Quantification of Hyperpolarized C-13 Metabolic Data (PI: Sarah Nelson, PhD) [GSK Contract/Clinical Trial; 12/15/11-12/14/16] 
  9. Response to Therapy for Patients with Glioma Using Hyperpolarized C-13 Pyruvate (PI: Sarah Nelson, PhD) [NIH R21 CA170148; 07/01/12-06/30/16 Project Goal: The goal is to perform an early phase clinical trial that will demonstrate the application of hyperpolarized C-13 MR metabolic imaging as a new and unique tool for detecting early response to therapy in patients with Glioblastoma (GBM). 
  10. In Vivo Metabolic Catastrophe Is Induced By Acute Oncogene Inhibition (PI: Andrei Goga, MD, PhD) [NIH/NCI R01 CA170447; 08/01/12-07/31/16] 
    Project Goal: To investigate the role of Oncogenes in cancer metabolic changes using a variety of tools including hyperpolarized carbon-13 MR. 
  11. Non-invasive Monitoring of Liver Inflammation and  Fibrosis Using Hyperpolarized Carbon-13 MRI (PI: Michael Ohliger, MD, PhD) [RSNA Research Scholar Grant RSCH1416; 07/01/14-06/30/16] 
    Project Goal: The goal of this project is to develop and apply specialized HP 13C methods for monitoring two important components of hepatitis-induced liver damage, fibrosis and inflammation, which is an unmet clinical need that will permit the non-invasive monitoring of liver disease and development of new treatments.
  12. Non-invasive Assessment of Macrophages Polarization Status in MS using Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging (PI: Myriam Chaumeil, PhD) [NMSS; 04/01/15-03/31/16] 
    Project Goal: The goal of this pilot project is to develop an innovative neuroimaging method that can provide unprecedented information on a specific type of immune cells, namely macrophages, in Multiple Sclerosis (MS).
  13. In vivo Imaging of Macrophages Polarization in Multiple Sclerosis using Hyperpolarized 13C MRSI of Pyruvate and Arginine (PI: Myriam Chaumeil, PhD) [UCSF REAC AWARD Springer Memorial Fund; 03/01/15-02/28/16] 
    Project Goal: The goal of this pilot project is to validate pyruvate and arginine as new HP probes to investigate macrophages polarization status in a preclinical model of Multiple Sclerosis (MS). 
  14. Ascorbate-based Biomarkers for Predicting Radiation Response in Prostate Cancer (PI: David Wilson, MD, PhD) [NIH R01 CA166766; 04/01/12-03/31/17] 
    Project Goal: This project seeks to develop and investigate new ascorbate-based hyperpolarized MRI biomarkers in preclinical animal models. This project also compares this cutting-edge MRI technology to a method already used in the clinic, positron emission tomography (PET) in order to address how these two complementary techniques might best serve the needs of cancer patients.
  15. Molecular Imaging for Detection and Treatment Monitoring of Arthritis (PI: John MacKenzie, MD) [NIH/NIAMS K08 AR061412; 07/01/12-06/30/17] 
    Project Goal: The overall goal of this mentor project mentored by Dr. John Kurhanewicz is to develop and study non-invasive imaging biomarkers for the detection and treatment monitoring of autoimmune disease.
  16. Using Hyperpolarized 13C Pyruvate to Assess Response in Pediatric Diffuse Intrinsic Pontine Glioma – A Non-Invasive Response Biomarker (PI: Sabine Mueller, MD) [UCSF RAP; 07/01/15-06/30/17] 
    Project Goal: To determine if the application of hyperpolarized 13C MR metabolic imaging can be used as a new imaging tool for detecting early response to therapy in children with diffuse intrinsic pontine glioma (DIPG) and serve therefore as a neuro-imaging biomarker for blood brain and blood tumor penetration of selected agents. 
  17. Improved Hyperpolarization of DHA for Clinically-Relevant Cellular-Redox Imaging (PI: Joseph Walish, PhD & Subcontract PI: John Kurhanewicz, PhD) [NIH STTR - Dynopol, Inc.; 01/06/17-06/18/17] 
    Project Goal: This Phase I effort will focus on increasing DHA polarization to clinically-relevant levels with Dynopol’s polarization agents.  Success (a 2x increase in polarization) will enable higher resolution and sensitivity in cellular-redox imaging using this non-invasive metabolite. 
  18. Hyperpolarized Arginine Imaging of Inflammatory Cells and Their Inhibition in GBM (PI: Sabrina Ronen, PhD) [NIH R21 CA201453; 12/01/15-11/30/18] 
    Project Goal: The proposed research will address the currently unmet need for a noninvasive method to monitor the presence of tumoral MDSCs and their immunosuppressive pro-tumoral activity, as well as the efficacy of MDSC-targeting immunotherapies in GBM.  This innovative imaging approach will provide an important tool to further understand the role of MDSCs in tumor development, and to assess the efficacy of emerging immunotherapies.  Beyond this study, our approach could also be used more broadly for imaging neuroflammatory diseases of the brain.  
  19. Metabolic Reprogramming in Brain Tumors (PI: Sabrina Ronen, PhD) [NIH R01 CA172845; 02/04/13-01/31/19] 
    Project Goal: The goal of this project is to test the hypothesis that the neomorphic activity of mutant isocitrate dehydrogenase (IDH) results not only in production of the oncometabolite 2-hydroxygluatarte (2-HG), but also in a wider metabolic reprogramming which is essential for tumor progression and therefore can be targeted in the treatment of IDH-mutant gliomas.
  20. Novel Hyperpolarized MR Makers of Advanced Prostate Cancer Therapy (PIs: John Kurhanewicz, PhD & Dan Vigneron, PhD) [NIH R01 CA166655; 09/30/12-07/31/18] 
    Project Goal: This project is focused on the preclinical development and testing of novel hyperpolarized carbon-13 MR techniques approaches for advanced prostate cancer characterization and treatment monitoring for future translation to the clinic.
  21. Imaging and Tissue Correlates to Optimize Management of Glioblastoma (PIs: Sarah Nelson, PhD & Susan Chang, MD) [NIH P01 CA118816; 07/01/13-06/30/18]
    Project Goal: The overall goal of the new P01 is to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma.  
  22. New Instrumentation and Techniques for Hyperpolarized Metabolic Perfusion MRI (PIs: Dan Vigneron, PhD & John Kurhanewicz, PhD) [NIH R01 EB013427 Bioengineering Research Grants (BRG); 07/15/13-05/31/18] 
    Project Goal: This Bioengineering Research grant project would seek to develop new multi-agent hardware and methods for dual polarizations of multiple compounds for future human studies.
  23. Hyperpolarized 13C MR Markers of Diabetic Nephropathy and Treatment Response (PI: Jane Wang, MD) [NIH/NIDDK R01 DK097357; 09/20/13-07/31/18] 
    Project Goal: The goal of this work is to develop hyperpolarized 13C magnetic resonance methods to noninvasively image the alterations in oxidative stress and glucose metabolism in vivo in diabetic nephropathy.
  24. Molecular Imaging of Renal Transport and Metabolism using Hyperpolarized C-13 MRI (PI: Cornelius von Morze, PhD) [NIH K01 DK099451; 04/01/14-03/31/19] 
    Project Goal: The overall goal of this project is to develop the application of new hyperpolarized carbon-13 (13C) MRI technology for monitoring renal disease. 
  25. Hyperpolarized 13C Diffusion MRI Measures of Novel Contrast, Transport and Metabolism (PI: Peder Larson, PhD) [NIH R01 EB016741; 09/15/14-05/31/18] 
    Project Goal: This project will develop and test new metabolite diffusion MRI methods to non-invasively measure metabolism and cellular transport.  Both of these mechanisms are highly implicated in aggressive types of cancer, as well as other diseases such as kidney failure and non-alcoholic fatty liver disease.  This method has significant potential to improve healthcare by better characterizing disease severity and improving outcome predictions following treatment. 
  26. Synergistic Idea Development Award Metabolic Reprogramming of Prostate Cancer and Antitumor Immunity by Targeting LDH-A (PI: Pankaj Seth, MD, PhD & Subcontract PI: John Kurhanewicz, PhD) [DOD PC140571P4; 07/01/15-06/30/18] 
    Project Goal: It is only when prostate cancer metastasizes beyond the gland that it becomes a lethal disease. The goal of this study is to combine a new molecular imaging technique, hyperpolarized 13C magnetic resonance imaging (MRI), with a new model of prostate cancer in which the LDH-A enzyme can be turned off (Cretm-LDH-Afl/fl;TRAMP) to determine whether the resulting reduction in tumor lactate will reduce the aggressiveness and metastatic potential of prostate cancer.  We will also determine whether inhibition of LDH-A function in immune cells has a causative role in inhibiting tumor progression in vivo.
  27. Prostate Cancer Research Program (PCRP) Physician Research Training Award Detection of Aggressive Prostate Tumors Using Novel PET and Hyperpolarized 13C Probes Targeting Interstitial Acidity (PI: Robert R. Flavell, PhD) [DOD PC150932; 07/01/15-06/30/18] 
    Project Goal: The goal of this proposal is to generate novel molecular imaging approaches targeting acidic interstitial pH to discriminate between high and low grade prostate cancers. Thus, we propose the validation of two imaging methods under development in our laboratory for this purpose. The first of these is based on hyperpolarized 13C spectroscopy, in which ACES, a common biological buffer with a large pH dependent 13C chemical shift, is administered and imaged by magnetic resonance spectroscopy. This method will allow us to generate in vivo pH maps with mm scale resolution. The second imaging method utilizes pro-drug derivatives of fluorodeoxyglucose (FDG), termed FDG amines, which decompose to form FDG when exposed to acid. This technique will allow us to generate whole body maps of areas of acidic interstitial pH. These innovative compounds provide complementary information – while FDG amines can provide a whole body map of sites of acidic pH, hyperpolarized ACES spectroscopy provides quantitative pH evaluation of selected anatomical regions. We will validate these methods by comparing against the current state of the art techniques for imaging interstitial pH. Finally, we will correlate the presence of acidic pH with histologically proven high-grade cancer and overall survival in TRAMP mice. These experiments set the stage for later investigations in human radical prostatectomy specimens, and ultimately for imaging in patients with prostate cancer.
  28. Development of Methodologies and Probes for Metabolic Detection of Pathogenic Microorganisms using Hyperpolarized Magnetic Resonance Technology (PI: Renuka Sriram, PhD) [REAC AWARD Springer Memorial Fund; 01/01/18-12/31/18] 
    Project Goal: The goal of this project is to develop hyperpolarized probes to enable metabolic detection of bacterial infection.
  29. Exploring Combined Hyperpolarized 13C MRI with Liver-specific Gadolinium Contrast Agents for Improved Metabolic Assessment of Liver Tumors (PI: Michael Ohliger, PhD) [NIH R21 EB023605; 07/01/17-06/30/19] 
    Project Goal: The goal of this R21 is to improve hyperpolarized 13C metabolic imaging of liver tumors by using a liver-specific gadolinium contrast agent that suppresses signal from normal background liver. 
  30. Bioengineering Research Partnerships (BRP) Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods (PIs: Daniel Vigneron, PhD & John Kurhanewicz, PhD) [NIH R01 EB017449; 08/15/13-07/31/18 NCE til 7/31/19] 
    Project Goal: This Bioengineering Research Partnership project aims to develop and translate new methods for human hyperpolarized carbon-13 MRI.
  31. Translating HP 13C MRI as a Novel Paradigm for Drug Target Inhibition (PIs: Daniel Vigneron, PhD & Pamela Munster, MD) [NIH R01 CA183071; 05/12/14-02/28/19 NCE til 2/28/20] 
    Project Goal: The goal of this academic-industrial collaborative research project is to accomplish the clinical translation of the “next-generation imaging technology” hyperpolarized 13C MRI to address the unmet clinical need of quantifying metabolic response to targeted therapy (e.g. mTOR pathway inhibitors) non-invasively in patients with advanced malignancies. 
  32. Imaging Age-related Changes in Energy Metabolism in Sarocomeric HCM (PI: Peder Larson, PhD & Roselle Abraham, MD) [MyoSeeds Research Grant Program; 02/26/19-02/25/20] 
    Project Goal: We propose to study the bioenergetics of HCM models of sarcomeric HCM at an established disease stage using basic studies and non-invasive imaging of metabolism and energetics. We will develop a new imaging strategy in mouse and humans, that combines hyperpolarized 13C MRI (a new metabolic imaging modality) and 31P MR spectroscopy (for assessing bioenergetics). The ultimate goal is to identify specific metabolic/energetic bio-signatures in HCM patients for pre-clinical diagnosis of HCM in families with known and unknown causal mutations, for development of therapies that prevent/reverse the cardiac HCM phenotype, permit individualization of therapy and assess response to therapy. Industry Grant with MyoKardia.
  33. Detection and Characterization of Treatment Emergent Neuroendocrine Prostate Cancer Using Hyperpolarized 13C Magnetic Resonance (PI: Renuka Sriram, PhD) [DOD PC160630; 03/22/17-03/21/20] 
    Project Goal: In this grant, we will test the hypothesis that key metabolic signatures underpinning neuroendocrine prostate cancer (NEPC) can be used to distinguish it from adenocarcinoma using hyperpolarized 13C MRI to develop a non-invasive imaging tool for early detection and appropriate therapeutic intervention.
  34. Metabolic Characterization of Prostate Cancer Bone Metastatic Phenotypes using Hyperpolarized 13C MRI – Improved Assessment of Therapeutic Response (PI: Renuka Sriram, PhD) [UCSF Prostate Cancer Program – Pilot Award; 04/01/19-06/30/20] 
    Project Goal: Initial feasibility assessment of intratibial tumor model of prostate cancer in mice and its imaging using HP 13C MRI to detect metabolic differences between phenotypes of prostate cancer. 
  35. Hyperpolarized 13C Metabolic Imaging for Preclinical Detection of Hypertrophic Cardiomyopathy (PIs: Peder Larson, PhD & Roselle Abraham MD) [UCSF RAP; 02/01/19-07/31/20] 
    Project Goal: This proposal seeks to establish methods using hyperpolarized 13C MR for non-invasive characterization of cardiac metabolism in mouse models of Hypertrophic Cardiomyopathy (HCM).
  36. Development of Methodologies and Probes for Metabolic Detection of Pathogenic Microorganism (PI: Renuka Sriram, PhD) [NIH R03 AI138189; 05/02/18-04/30/21] 
    Project Goal: The overall goal of this proposal is to evaluate bacteria specific imaging using hyperpolarized carbon-13 MR.    

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