Remus Albu¹, Daniel Elgort¹, Khalid shahzad¹, Ramon Erkamp¹, Shiwei Zhou¹, and Jean-Luc Robert^1
1Philips Research N.A., Briarcliff Manor, NY, United States

A novel hyperpolarization approach is presented that uses a photon beam endowed with orbital angular momentum (OAM) to induce nuclear hyperpolarization in liquids at room temperature. The feasibility of this hyperpolarization method was verified experimentally by irradiating small volumes of 1H and 19F – rich liquid samples with a focused OAM beam endowed with OAM charges of 0 to ±20. The NMR signal level for “light off” and OAM=0 conditions were comparable, while the NMR signal level increased with the absolute value of the OAM charge. The nuclear magnetic polarization of the fluid sample inside the focal spot of the OAM beam was estimated to be between ~1.5% and 5%.

Kilian Weiss¹, Andreas Sigfridsson¹, Georgios Batsios¹, Marcin Krajewski¹, Michael Batel², and Sebastian Kozerke^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Physical Chemistry, ETH Zurich, Zurich, Switzerland

The investigation of real-time metabolic processes using hyperpolarized compounds requires efficient sampling schedules for sufficient spatiotemporal resolutions. Dynamic hyperpolarized 13C signals in the heart are inherently sparse and their dynamics may be represented by few temporal basis functions. To this end, spatiotemporal acceleration techniques are particularly suited to speed up acquisitions. In this work k-t PCA was implemented and tested based on simulated and hyperpolarized in-vivo data of the rat heart. Accurate reconstructions from up to 8-fold k-t undersampled data have been achieved demonstrating the potential of k-t undersampling approaches for dynamic hyperpolarized imaging of the heart.

Cornelius von Morze¹, Robert A Bok¹, Jeff M Sands², John Kurhanewicz¹, and Daniel B Vigneron^1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, United States, ²Department of Medicine, Emory University, Atlanta, Georgia, United States

Urea functions as a key osmolyte in the urinary concentrating mechanism of the renal inner medulla. The urea transporter UT-A1 is upregulated by antidiuretic hormone, facilitating faster equilibration of urea between the lumen and interstitium of the inner medullary collecting duct, resulting in the formation of more highly concentrated urine. New methods in dynamic nuclear polarization, providing ~50,000-fold enhancement of NMR signals in the liquid state, offer a novel means to monitor this process in vivo using MRI. In this study, we detected significant signal differences in the rat kidney between acute diuretic and antidiuretic states, using dynamic ¹³C MRI following a bolus infusion of hyperpolarized [¹³C]urea. More rapid medullary enhancement was observed under antidiuresis, consistent with known upregulation of UT-A1.

Sarah E Bohndiek^1,2, Mikko I Kettunen^1,2, David Lewis², Tiago B Rodrigues^1,2, Ferdia A Gallagher^1,2, Dmitry Soloviev², and Kevin M Brindle^1,2
1Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ²Cambridge Research Institute, Cancer Research UK, Cambridge, Cambridgeshire, United Kingdom

Hyperpolarized [1-¹³C]-Dehydroascorbic Acid (DHA) has recently been demonstrated as a novel imaging biomarker of tumor redox status in vivo. We show here that the rate of [1-¹³C]-DHA reduction is also influenced by glucose transporter expression, so care should be taken to assess the effect of DHA transport on imaging studies performed with this promising hyperpolarized probe.

Trevor Wade^1,2, Hyla Allouche-Arnon^3,4, Lanette Friesen Waldner^1,5, Charles A McKenzie^1,5, Kundan Thind^1,5, Alexei Ouriadov⁵, Albert Chen⁶, J. Moshe Gomori³, and Rachel Katz-Brull^3,4
1Medical Biophysics, The University of Western Ontario, London, Ontario, Canada, ²XLR Imaging, London, Ontario, Canada, ³Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, ⁴BrainWatch Ltd, Tel-Aviv, Israel, ⁵Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada, ⁶GE Healthcare

The first noninvasive and nonradioactive imaging of choline labelled at position 1 with hyperpolarized ¹³C is presented as well as monitoring of its metabolism in a specific organ (the kidney) in the living rat. The chemical shift between choline and phosphocholine is sufficient to monitor the kinetics of choline metabolism using dynamic spectroscopy. Imaging and 2D CSI are also used to monitor regional choline uptake and the metabolic products.

Myriam Marianne Chaumeil¹, Sarah Woods¹, Robert M Danforth¹, Hikari Yoshihara¹, Alessia Lodi¹, Aaron Robinson², Joanna J Philips^2,3, and Sabrina M Ronen^1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States, ³Pathology, University of California, San Francisco, San Francisco, CA, United States

The mutational status of isocitrate dehydrogenase (IDH1) was assessed using dynamic ¹³C MRS of hyperpolarized (HP) -ketoglutarate in two glioblastoma cells lines: U87 transduced with IDH1 wild-type (U87IDHwt) or IDH mutant (U87IDHmut). Following injection of HP -KG, HP 2-hydroxyglutarate and HP glutamate were detected in U87IDHmut lysates. Only HP glutamate was visible in U87IDHwt lysates. Injection of HP -KG in live perfused U87IDHwt cells resulted in dynamic HP glutamate build-up whereas no HP glutamate was detected in perfused U87IDHmut cells. This pioneer study demonstrates that HP -KG can inform on IDH mutational status through the dynamic assessment of its metabolism.

XIAOMENG ZHANG¹, Dutta Prasanta¹, Gary Martinez¹, N V Rajeshkumar², A Le², A Maitra², C V Dang², and Robert J Gillies^1
1cancer imaging, Moffitt cancer center, TAMPA, FL - Florida, United States, ²School of Medicine, Johns Hopkins University, Baltimore, MD, United States

Development of novel targeted anti-cancer therapies is highly dependent on qualified in-vivo biomarkers for the therapeutic response. Small molecule drug FX11 that inhibits the lactate dehydrogenase A (LDHA) alters cellular energy metabolism, and reduces the tumor progression1. This procedure could be captured in-vivo by monitoring the metabolic conversion rate of 13C-labled substrates using dynamic nuclear polarization (DNP)2. This measurement could be compared with the most common imaging response biomarker: diffusion-weighted MRI (DW-MRI), which is a measure of tumor cellularity. The apparent diffusion coefficient (ADC) of tumors calculated from DW-MRI has been shown to be valuable for predicting early response to therapies in a variety of cancers3. The purpose of this study is to demonstrate the dynamics of metabolic conversion from 13C pyruvate to 13C lactate with FX11 treatment and compare the ability of two response biomarkers: hyperpolarized (HP) 13C-labled magnetic resonance spectroscopy (MRS) and DW-MRI in the drug sensitive tumor Panc253.

PHILIP LEE¹, MAEGAN LIM², WEIPING HAN², and GEORGE RADDA^1
1FUNCTIONAL METABOLISM GROUP, SINGAPORE BIOIMAGING CONSORTIUM, SINGAPORE, SINGAPORE, Singapore, ²LAB OF METABOLIC MEDICINE, SINGAPORE BIOIMAGING CONSORTIUM, SINGAPORE, SINGAPORE, Singapore

Non-alcoholic fatty liver disease (NAFLD) induces changes in liver metabolism. In order to measure such functional aberration, we injected hyperpolarized carbon-13-labeled pyruvate into a mouse model of hepatic steatosis and followed its metabolism in real-time and in-vivo. Initial results showed elevation in malate and aspartate levels, suggesting an increase in pyruvate carboxylase flux. Glucose tolerance test reveals glucose intolerance, a harbinger of diabetes. Quantification of pyruvate carboxylase flux via hyperpolarized pyruvate, as well as measures of downstream malate and aspartate metabolite pools could serve as alternative biomarkers of hepatic steatosis.

Angus Z. Lau^1,2, Albert P. Chen³, William Dominguez-Viqueira², Marie A. Schroeder^2,4, Yiping Gu², Jennifer Barry², John Graham^2,5, Nilesh Ghugre², Graham A. Wright^1,2, and Charles H. Cunningham^1,2
1Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ²Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, ³GE Healthcare, Toronto, Ontario, Canada, ⁴Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom,⁵Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada

A dual respiratory and cardiac-gated, multi-slice, single-shot spiral frequency-specific 13C pulse sequence was used to characterize cardiac metabolic remodeling following acute myocardial infarction in vivo in a porcine ischemia-reperfusion model. We observed two distinct phenotypes, corresponding to myocardial stunning and infarction, with distinct metabolic remodeling patterns revealed by hyperpolarized 13C imaging. PDH flux was reduced following LAD occlusion, with recovery in stunned myocardium. Elevated myocardial lactate was observed in the peri-infarct region, presumably reflecting the potential viability of the myocardium in that area. This work may potentially enable a clinically feasible assessment of salvageable myocardium (the area-at-risk) in myocardial infarction.

Sarah J. Nelson^1,2, John Kurhanewicz³, Daniel B. Vigneron⁴, Peder Larson⁴, Andrea Harzstarck⁴, Marcus Ferrone⁴, Mark van Criekinge⁴, Jose Chang⁴, Robert Bok⁴, Ilwoo Park⁴, Galen Reed⁴, Lucas Carvajal⁴, Jason Crane⁴, Jan Henrik Ardenkjaer-Larsen⁵, Albert Chen⁶, Ralph Hurd⁷, Liv-Ingrid Odegardstuen⁸, and James Tropp^7
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States, ³University of California, San Francisco, United States, ⁴University of California, San Francisco, ⁵General Electric Healthcare, Denmark, ⁶General Electric Healthcare, Toronto, Canada, ⁷General Electric Healthcare, Fremont, CA, USA, ⁸General Electric Healthcare, Oslo, Norway

The first clinical trial using C-13 MR metabolic imaging has been successfully performed in patients with biopsy proven prostate cancer. In this dose escalation study 31 patients received an injection of 250mM hyperpolarized C-13 pyruvate, followed by metabolic imaging at 3T. Dynamic data showed arrival of C-13 pyruvate approximately 20 seconds after injection and demonstrated that the T1 was long enough to detect uptake and conversion to lactate for 60+ seconds. There were no dose limiting toxicities observed. The highest dose of 0.43mL/Kg gave the best lactate SNR and contrast in lactate/pyruvate for tumor relative to normal prostate.