Bertram L Koelsch1,2, Galen D Reed1,2, John Kurhanewicz1,2, Peder E Z Larson1,2, Kayvan R Keshari3, Myriam M Chaumeil1, Robert Bok1, Sabrina M Ronen1,2, Daniel B Vigneron1,2. 1. Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA. 2. UC Berkeley - UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, California, USA. 3. Department of Radiology and Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, USA.
Abstract
PURPOSE: Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. METHODS: We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. RESULTS: We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware. CONCLUSION: ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential.
PURPOSE: Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) Clactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) Clactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. METHODS: We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. RESULTS: We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, ratbrain tumor, and prostate cancermouse model using both preclinical and clinical trial-ready hardware. CONCLUSION:ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential.
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