Andrea Capozzi^1,2, Jan Kilund¹, Magnus Karlsson¹, Mathilde Hauge Lerche¹, and Jan Henrik Ardenkjaer-Larsen^1
1Health Technology, Danish Technical University, Kongens Lyngby, Denmark, ²IPHYS, EPFL, Lausanne, Switzerland

Our vision is to enable delivery of hyperpolarized compounds to MR-facilities that currently have no access to hyperpolarization technology. Today this is not the case and represents a main shortcoming of hyperpolarized-MR via dissolution Dynamic Nuclear Polarization (dDNP). The cause is the presence, in the dDNP sample, of organic free radicals necessary to generate the hyperpolarization. We herein present a paradigm shift in the technique built on the employment of photo-induced thermally-labile free radicals. We demonstrate quenching of the paramagnetic species while preserving most of the polarization in the case of hyperpolarized glucose.

Andreas Dounas¹, Valery Vishnevskiy¹, Maximilian Fuetterer¹, Julia Traechtler¹, and Sebastian Kozerke^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

A variational network (VN) was implemented and trained on synthetic data to reconstruct multi-echo hyperpolarized ¹³C data acquired in the in vivo heart. VN reconstruction performance was studied using 2D and 3D synthetic data under low SNR conditions and for acceleration factors of 3 and 9, respectively. Relative to standard gradient descent based reconstruction, the network offers improved reconstruction accuracy and reduced signal leakage between metabolites while preserving information on lactate-to-bicarbonate ratios.

Shuyu Tang¹, Robert Bok¹, Hecong Qin¹, Galen Reed², Mark VanCriekinge¹, Romelyn Delos Santos¹, William Overall², Juan Santos², Jeremy Gordon¹, Zhen J. Wang¹, Daniel Vigneron¹, and Peder E.Z. Larson^1
1University of California, San Francisco, San Francisco, CA, United States, ²HeartVista, Los Altos, CA, United States

This work describes a novel 3D bSSFP sequence that integrates a lactate specific excitation pulse and stack-of-spiral readouts for improved lactate dynamic imaging in hyperpolarized [1-¹³C]pyruvate studies on a clinical 3T scanner. Compared with metabolite specific GRE sequences, the MS-3DSSFP sequence showed an overall 2.5X SNR improvement for lactate imaging in rat kidneys, tumors of TRAMP mice and human kidneys.

James Timothy Grist^1,2, Esben S Hansen³, Juan D Sanchez⁴, Mary A McLean⁵, Frank Riemer⁶, Rolf F Schulte⁷, Jan Henrik Ardenkjaer-Larsen⁴, Christoffer Laustsen³, and Ferdia A Gallagher^6
1Unviesity of Cambridge, Cambridge, United Kingdom, ²University of Birmingham, Birmingham, United Kingdom, ³Aarhus University, Aarhus, Denmark, ⁴Technical University of Denmark, Copenhagen, Denmark, ⁵Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United Kingdom, ⁶University of Cambridge, Cambridge, United Kingdom, ⁷GE Healthcare, Munich, Germany

Hyperpolarized ¹³C MRI is an emerging clinical technique to probe metabolism. Calibration of transmit gain and centre frequency is challenging, due to the low endogenous ¹³C signal. Pre-scan is typically performed by adding an external phantom for reference, however this is challenged by the shim volume inside the subject and the RF coil excitation and receptions profiles. We demonstrate the ability to use the sodium-23 resonance to accurately prescan prior to ¹³C experiments, using single tuned ¹³C coils in a 3T MRI system. This provides an important workflow improvement for the adoption of hyperpolarized ¹³C imaging into clinical practise.

Edward P Hackett¹, Marco C Pinho², Crystal E Harrison¹, Galen D Reed³, Surendra Barshikar⁴, Christopher J Madden⁵, and Jae Mo Park^1,2,6
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ³GE Healthcare, GE Healthcare, Dallas, TX, United States, ⁴Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁵Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁶Electrical Engineering, University of Texas Dallas, Richardson, TX, United States

A major challenge of treating traumatic brain injury (TBI) patients is the simultaneously occurring complex secondary injury processes following the primary injury. The secondary events such as cerebral hyperglycolysis and mitochondrial failure develop over minutes to months after the primary injury. This case report details the first time hyperpolarized [1-¹³C]pyruvate imaging in TBI patients to examine regional metabolic changes in the brain post-traumatic injury. We observed an increased conservation of pyruvate to lactate at the injured sites as well as reduced bicarbonate production.

Casey Y Lee^1,2, Hany Soliman³, Nadia D Bragagnolo^1,2, Albert P Chen⁴, William J Perks⁵, Chris Heyn⁶, Sandra E Black⁷, and Charles H Cunningham^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ³Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴GE Healthcare Technologies, Toronto, ON, Canada, ⁵Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁶Radiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁷Department of Medicine (Neurology) and Hurvitz Brain Sciences Research Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Hyperpolarized [1-¹³C]lactate and ¹³C-bicarbonate images were acquired with and without spectral-spatial lactate saturation in the brains of control participants. A previously published atlas-based analysis was used to convert [1-¹³C]lactate and ¹³C-bicarbonate signals into z-scores to quantify the effect of [1-¹³C]lactate saturation. The analysis showed that lactate z-scores were changed in the saturation regions, as expected. The saturation of [1-¹³C]lactate signals did not significantly affect ¹³C-bicarbonate signals.

Mehrdad Pourfathi¹, Hooman Hamedani^1,2, Yi Xin^1,2, Michael Rosalino¹, Stephen J Kadlecek¹, Ian Duncan¹, Maurizio Cereda^1,3, Sarmad Siddiqui¹, Harrilla Profka¹, Luis Loza¹, Faraz Amzajerdian ^1,2, Tahmina Achekzai¹, Kai Ruppert¹, Federico Sertic^1,4, Ryan Baron¹, Jon Snow¹, Yiwen Qian^1,2, Gabriel Unger¹, Shampa Chatterjee⁵, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, ³Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States, ⁴Surgery, University of Pennsylvania, Philadelphia, PA, United States, ⁵Physiology, University of Pennsylvania, Philadelphia, PA, United States

Transpulmonary lactate gradient is strongly correlated with the severity of lung injury and inflammation in ARDS patients. Hyperpolarized [1-¹³C] pyruvate MRI allows us to quantitatively study altered pyruvate-to-lactate conversion in cancerous and inflamed tissues. We sought to demonstrate the translational potential of this technology for pulmonary metabolic imaging in humans. We performed [1-¹³C] pyruvate lung MRI in an experimental model of aspiration pneumonitis in pigs, demonstrating this technology’s capacity to detect changes in pulmonary anaerobic metabolism after inflammatory injury in larger species.

Paul Begovatz¹, Sarah Erickson-Bhatt^2,3,4, Benjamin Cox², Suzanne Ponik⁴, Kevin Eliceiri^1,2,3, and Sean Fain^1,5,6
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Morgridge Institute for Research, Madison, WI, United States, ³Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI, United States, ⁴Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, United States, ⁵Radiology, University of Wisconsin-Madison, Madison, WI, United States, ⁶Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States

Hyperpolarized ¹³C-Magnetic resonance spectroscopy (¹³C-MRS) and NADH fluorescence lifetime imaging (FLIM) have evolved as methods to detect metabolic shifts in aerobic glycolysis and oxidative phosphorylation which are associated with metastatic potential in cancer metabolism. This study set out to investigate the differences in cancer metabolism between murine non-metastatic, metastatic-dormant, and highly metastatic breast cancer cell lines. FLIM analysis revealed no differences in free and bound NADH between cell lines, indicative of uniform ATP production through oxidative phosphorylation; however, hyperpolarized ¹³C-MRS measurements detected an increase in lactate production, or aerobic glycolysis, which was associated with greater breast cancer metastatic potential.

Roozbeh Eskandari¹, Arsen Mamakhanyan¹, Kristin L Granlund¹, Kayvan R Keshari¹, and Craig B Thompson^2
1Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, United States

Aberrations in glutaminase enzyme expression are associated with a variety of pathologies, and an in vivo probe to quantify flux through this pathway may provide a new layer of information. We developed a custom-synthesized compound, [5-¹³C,4-²H₂,5-¹⁵N­]-L-Glutamine, as a hyperpolarized MRI probe for glutaminase activity. Triple labeling of glutamine and D₂O solvation reduces quadrupolar relaxation and extends both T₁ and T₂, facilitating in vivo imaging. We were able to acquire ¹³C spectroscopic data on a subcutaneous RCC xenograft murine model and detect in vivo conversion of hyperpolarized glutamine to glutamate, which permits further exploration of this imaging probe in the future.

Hikari A. I. Yoshihara¹ and Juerg Schwitter^2,3
1Laboratory for Functional and Metabolic Imaging, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland, ²Division of Cardiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland, ³Cardiac MR Center, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland

Renal gluconeogenesis contributes to glucose homeostasis and is elevated in diabetes. Aspartate is an efficient gluconeogenic substrate in the kidney, and its conversion to glucose proceeds via phosphoenolpyruvate carboxykinase (PEP-CK), which is a rate-limiting enzyme. Scanning the kidney of rats infused with hyperpolarized [1-¹³C]aspartate, the metabolites detected include  [1-¹³C]malate and  [4-¹³C]malate, 3-phospho[1-¹³C]glycerate, and a trace of bicarbonate. Using [1,4-¹³C₂]aspartate resulted in higher bicarbonate signal, consistent with PEP-CK activity, and bicarbonate was undetectable after inhibiting PEP-CK. Compared to fed rats, the bicarbonate-to-malate ratio was 3-fold higher in fasted rats, indicating the potential of hyperpolarized aspartate to probe renal gluconeogenesis.