Hyperpolarized (HP) carbon-13 MRI has demonstrated the ability to significantly advance our understanding of disease processes and the great potential to become a cost effective molecular imaging tool for monitoring clinical trial and individual patient management. Our recent first-in-man Phase 1 Clinical Trial utilized unique dissolution DNP instrumentation and methods for [1-13C] pyruvate metabolic imaging. The proposed project is designed to take a major step forward by developing new instrumentation and methods to translate preclinical multi-agent polarization studies into first-in-man dual-agent simultaneous metabolic &perfusion HP MRI studies. This project aims to develop a new MRI approach to characterize cancers based on their genetic/proteomic and perfusion abnormalities and apply this method in preclinical models to obtain the required preliminary data for FDA approval and then to conduct initial human studies. Hyperpolarized (HP) carbon-13 MRI is a powerful new molecular imaging method which uses specialized instrumentation to provide signal enhancements of over 5-orders of magnitude for carbon-13 enriched, safe, endogenous, non-radioactive compounds. Co-polarization of 13C-urea with [1-13C] pyruvate provides not only an internal reference for improved quantitative accuracy, but also a method for simultaneous perfusion measurements without ionizing radiation and without the nephrotoxicity effects of other perfusion contrast agents. This project aims to translate and perform first-in-man HP dual-agent perfusion &metabolic MRI to address a pressing clinical need, specifically improved radiological characterization of prostate cancer aggressiveness and treatment response. New hardware/instrumentation will be designed and constructed to enable dual-agent functionality necessary for first-in-man hyperpolarized perfusion and metabolic imaging human studies. Novel MRI acquisition and analysis methods will also be developed for acquiring rapid high resolution metabolic &perfusion imaging data. The techniques developed in this project will be applied in prostate cancer patients to address a clear unmet clinical need. However, these dual-agent HP 13C MR techniques also have general applicability to advance the clinical research of other cancers and potentially a wide range of pathologies including cardiac, liver, and kidney disease.
The successful outcome of the proposed project will result in the development of new instrumentation and methods for dual-agent MR molecular imaging of both perfusion and metabolism simultaneously. This project also includes translation into the clinical setting with a first-ever feasibility study of these methods in prostate cancer patients. While this project focuses on prostate cancer, these new molecular imaging techniques could ultimately benefit the clinical management of other cancers and diseases.
|Park, I; Nelson, S J; Talbott, J F (2016) In Vivo Monitoring of Rat Spinal Cord Metabolism Using Hyperpolarized Carbon-13 MR Spectroscopic Imaging. AJNR Am J Neuroradiol 37:2407-2409|
|Park, Ilwoo; von Morze, Cornelius; Lupo, Janine M et al. (2016) Investigating tumor perfusion by hyperpolarized (13) C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts. Magn Reson Med :|
|Ohliger, Michael A; von Morze, Cornelius; Marco-Rius, Irene et al. (2016) Combining hyperpolarized (13) C MRI with a liver-specific gadolinium contrast agent for selective assessment of hepatocyte metabolism. Magn Reson Med :|
|Sriram, Renuka; Van Criekinge, Mark; DeLos Santos, Justin et al. (2016) Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized (13)C pyruvate magnetic resonance. Tomography 2:35-42|
|Shang, Hong; Sukumar, Subramaniam; von Morze, Cornelius et al. (2016) Spectrally selective three-dimensional dynamic balanced steady-state free precession for hyperpolarized C-13 metabolic imaging with spectrally selective radiofrequency pulses. Magn Reson Med :|
|Shang, Hong; Skloss, Timothy; von Morze, Cornelius et al. (2016) Handheld electromagnet carrier for transfer of hyperpolarized carbon-13 samples. Magn Reson Med 75:917-22|
|Shang, Hong; Larson, Peder E Z; Kerr, Adam et al. (2016) Multiband RF pulses with improved performance via convex optimization. J Magn Reson 262:81-90|
|Feng, Yesu; Gordon, Jeremy W; Shin, Peter J et al. (2016) Development and testing of hyperpolarized (13)C MR calibrationless parallel imaging. J Magn Reson 262:1-7|
|Shin, Peter J; Larson, Peder E Z; Uecker, Martin et al. (2015) Chemical shift separation with controlled aliasing for hyperpolarized (13) C metabolic imaging. Magn Reson Med 74:978-89|
|Sriram, Renuka; Van Criekinge, Mark; Hansen, Ailin et al. (2015) Real-time measurement of hyperpolarized lactate production and efflux as a biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor. NMR Biomed 28:1141-9|
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