ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Hyperpolarised MR & Metabolism

Wednesday, May 11, 2016
Room 331-332
13:30 - 15:30
Moderators: Christoffer Laustsen, Yi-Fen Yen

Hyperpolarized 13C-Urea MRI for the assessment of the urea gradient in the porcine kidney
Esben Søvsø Szocska Hansen1,2, Neil James Stewart3, Jim Michael Wild3, Hans Stødkilde-Jørgensen1, and Christoffer Laustsen1
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.

In vivo measurement of Renal Redox Capacity in a Model of Chronic Kidney Disease using by hyperpolarized 13C dehydroascorbate (DHA) MRS - Permission Withheld
Celine A.J. Baligand1, David H. Lovett2, Lalita Uttarwar2, Jeremy Gordon1, John Kurhanewicz1, David M. Wilson1, and Zhen Jane Wang1
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.

Maternal-fetal exchanges characterized by dynamic hyperpolarized 13C imaging on pregnant rats
Anne Fages1, Tangi Roussel1, Marina Lysenko2, Ron Hadas2, Michal Neeman2, and Lucio Frydman1
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.

Metabolic imaging of energy metabolism in traumatic brain injury using hyperpolarized [1-13C]pyruvate
Stephen J DeVience1, Xin Lu1, Julie Proctor2, Parisa Rangghran2, Rao Gullapalli1, Gary M Fiskum2,3,4, and Dirk Mayer1
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.

In Vivo pH and Metabolite MR Imaging Using Hyperpolarized 13C-Pyruvate
Nicholas Drachman1, Stephen J. Kadlecek1, Mehrdad Pourfathi1,2, Yi Xin1, Harrilla Profka1, and Rahim R. Rizi1
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.

Tumor Progression, Regression, and Recurrence Monitoring using Hyperpolarized [1-13C]Pyruvate Metabolic Imaging in a Murine Breast Cancer Model
Peter jinwoo Shin1, Zihan Zhu1, Roman Camarda2, Robert Bok1, Alicia Zhou2, Andrei Goga2, and Daniel B Vigneron1
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.

Metabolism of hyperpolarized 13C-acetoacetate/ß-hydroxybutyrate reveals mitochondrial redox state in perfused rat hearts
Wei Chen1, Chalermchai Khemtong1, Weina Jiang1, Craig R. Malloy1, and A. Dean Sherry1
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.

Detection of inflammatory cell function using 13C MRS of hyperpolarized 13C-labeled arginine
Chloe Najac1, Myriam M Chaumeil1, Gary Kohanbash2, Caroline Guglielmetti3, Jeremy Gordon1, Hideho Okada2, and Sabrina M Ronen1
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.

Initial experiences of simultaneous in vivo metabolic imaging using MRI, PET, and hyperpolarized 13C MRSI from rat glioma models
JAE MO PARK1, Shie-Chau Liu1, Milton Merchant2, Taichang Jang2, Keshav Datta1, Praveen Gulaka1, Zachary Corbin2, Ralph E Hurd3, Lawrence Recht2, and Daniel M Spielman1
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.

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