Esben Søvsø Szocska Hansen^1,2, Neil James Stewart³, Jim Michael Wild³, Hans Stødkilde-Jørgensen¹, and Christoffer Laustsen^1
1MR Research Centre, Aarhus University, Aarhus N, Denmark, ²Danish Diabetes Academy, Odense, Denmark, ³Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom

Renal anatomical and pathophysiological alterations are directly associated with the fluid and electrolyte balance in the kidney, which is regulated by the extracellular corticomedullary osmolality gradient. We introduce a novel magnetic resonance imaging (MRI) approach to monitor the corticomedullary osmolality gradient changes using hyperpolarized ¹³C-urea in a healthy porcine model. A corticomedullary urea gradient was observed with an intra-medullary accumulation after 75s of hyperpolarized ¹³C-urea injection, while earlier time points were dominated by cortical perfusion. Furosemide treatment resulted in an increased urea accumulation in the cortical space. This work demonstrates intra-renal functional assessment with hyperpolarized ¹³C-urea MRI in multi-papillary kidneys.

Celine A.J. Baligand¹, David H. Lovett², Lalita Uttarwar², Jeremy Gordon¹, John Kurhanewicz¹, David M. Wilson¹, and Zhen Jane Wang^1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Medicine, San Francisco Department of Veterans Affairs Medical Center/University of California San Francisco, San Francisco, CA, United States

Limited biomarkers are available for early diagnosis and monitoring of chronic kidney disease (CKD). Renal oxidative stress is a key initiator of CKD. Therefore, in vivo assessment of kidney redox capacity may provide a clinically relevant and early marker of kidney injury. The N-terminal truncated matrix metalo-protease isoform (NTT-MMP-2) transgenic mouse is a model mimicking human progressive kidney disease that is triggered by oxidative stress.  Using this model, we show that hyperpolarized ¹³C-dehydroascobic acid MRS imaging can detect in vivo the altered redox capacity preceding any functional and histological changes, thus potentially providing an early marker of susceptibility to CKD.

Anne Fages¹, Tangi Roussel¹, Marina Lysenko², Ron Hadas², Michal Neeman², and Lucio Frydman^1
1Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ²Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

Dynamic nuclear polarization (DNP) enhanced ¹³C MRI of hyperpolarized (HP) urea and bicarbonate has been applied to monitor metabolic fluxes from the maternal blood pool to the fetuses, in pregnant rats at late gestation stage. This use of HP metabolites offers a non-invasive way to observe details of active and passive maternal-fetal exchanges.

Stephen J DeVience¹, Xin Lu¹, Julie Proctor², Parisa Rangghran², Rao Gullapalli¹, Gary M Fiskum^2,3,4, and Dirk Mayer^1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States, ²Anesthesiology, University of Maryland, Baltimore, MD, United States, ³Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD, United States, ⁴Pharmacology, University of Maryland, Baltimore, MD, United States

We investigated the use of hyperpolarized ¹³C-pyruvate imaging as a direct, non-invasive method for identifying traumatic brain injury and studying its effects on energy metabolism. Rats were injured with a controlled cortical impact device and then injected with [1-¹³C]pyruvate. Spectrally-resolved imaging was performed on the brain to quantify the resulting pyruvate, lactate, and bicarbonate signals. The ratio of lactate to bicarbonate signal was found to be sensitive to traumatic brain injury, with the relative increase in lactate signal and decrease in bicarbonate (formed from CO₂) at the injury site suggesting a transition to anaerobic respiration.

Nicholas Drachman¹, Stephen J. Kadlecek¹, Mehrdad Pourfathi^1,2, Yi Xin¹, Harrilla Profka¹, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, United States

In this study, we investigate the possibility of simultaneously imaging pH and lactate to pyruvate ratio in vivo in the lungs. We produce hyperpolarized ¹³C-bicarbonate by rapidly decarboxylating hyperpolarized [1-¹³C]pyruvate with hydrogen peroxide. By tuning the reaction rate by altering the pH, we produce roughly equal amounts of pyruvate and bicarbonate, which allows us to image both metabolic processes simultaneously.

Peter jinwoo Shin¹, Zihan Zhu¹, Roman Camarda², Robert Bok¹, Alicia Zhou², Andrei Goga², and Daniel B Vigneron^1
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Biomedical Science Program, University of California, San Francisco, San Francisco, CA, United States

We used hyperpolarized [1-¹³C]pyruvate imaging to monitor tumor progression and regression in a murine breast cancer model that conditionally expresses the human c-MYC transgene in a doxycycline switchable manner. Previously, it was shown that this model could develop a secondary tumor even after the primary tumor regresses nearly fully following c-MYC deinduction. Hence, the purpose of this project was to monitor altered glycolytic metabolism by hyperpolarized metabolic MRI in this multi-stage mammary tumorigenesis animal model.

Wei Chen¹, Chalermchai Khemtong¹, Weina Jiang¹, Craig R. Malloy¹, and A. Dean Sherry^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

A large prior literature on inter-conversion of β-hydroxybutyrate (β-HB) and acetoacetate (AcAc) indicates that the process is mitochondrial and the ratio reflects specifically mitochondrial redox state.  Therefore the conversion of [1,3-¹³C]AcAc to [1,3-¹³C]β-HB is expected to be sensitive to redox.  In this study, we explored the utility of using hyperpolarized [1,3-¹³C]AcAc to study the mitochondrial redox state in perfused rat hearts. Our results show that the production of HP β-HB from HP-AcAc was much higher in ischemic hearts, reflecting the increased concentration of NADH under this reduced state. The redox-dependent conversion between this metabolic pair in mitochondria may lead to the development of an imaging tool for redox imaging of the heart by hyperpolarized ¹³C MRI.

Chloe Najac¹, Myriam M Chaumeil¹, Gary Kohanbash², Caroline Guglielmetti³, Jeremy Gordon¹, Hideho Okada², and Sabrina M Ronen^1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, ³Bio-Imaging Lab, University of Antwerp, Antwerpen, Belgium

Myeloid-derived suppressor cells (MDSCs) are inflammatory cells in the tumor microenvironment that inhibit T-cell-mediated immunosuppression by expressing high levels of arginase. Arginase catalyzes the breakdown of arginine into urea. To monitor the enzymatic conversion, we developed a new hyperpolarized (HP) probe, namely [guanido-¹³C]-arginine. We first characterized the probe and confirmed the production of HP ¹³C urea in solution with different arginase concentrations. Then, we demonstrated its potential to probe the increase in arginase activity in MDSCs. This new HP probe could serve as a readout of MDSC function in tumor and its inhibition following MDSC-targeted immunotherapies.

JAE MO PARK¹, Shie-Chau Liu¹, Milton Merchant², Taichang Jang², Keshav Datta¹, Praveen Gulaka¹, Zachary Corbin², Ralph E Hurd³, Lawrence Recht², and Daniel M Spielman^1
1Radiology, Stanford University, Stanford, CA, United States, ²Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States, ³Applied Sciences Laboratory, GE Healthcare, Menlo Park, CA, United States

We demonstrated the feasibility of simultaneous investigation of in vivo metabolism using ¹H MRI, time-of-flight ¹⁸F-FDG PET, and hyperpolarized ¹³C-pyruvate MRSI in C6 xenograft and ENU-induced brain tumor models. Volumetric images were acquired, and metabolic kinetics of FDG and pyruvate metabolism was investigated in the study.