Thanh Phong Lê^1,2, Emma Wiström², Jean-Noël Hyacinthe¹, and Andrea Capozzi^2,3
1Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland, ²Laboratory of Functional and Metabolic Imaging, EPFL (Swiss Federal Institute of Technology in Lausanne), Lausanne, Switzerland, ³Department of Health Technology, Center for Hyperpolarization in Magnetic Resonance, Technical University of Denmark, Kgs Lyngby, Denmark

Low throughput is one of dDNP main shortcomings. Here, we present the design and performance of a triple DNP probe, which not only allows multiple samples to be hyperpolarized simultaneously, but also to distinctly monitor the solid-state polarization of each sample, even when prepared with different nuclei and radicals. This versatile high throughput probe allows parallel solid-state sample characterization, as well as sequential injections of distinct tracers to probe multiple biomarkers, thus enabling more advanced in-vivo experimental designs.

Nikolaj Bøgh¹, Camilla W Rasmussen¹, Lotte B Bertelsen¹, Esben SS Hansen¹, and Christoffer Laustsen^1
1Aarhus University, Aarhus, Denmark

In hyperpolarized [1-¹³C]pyruvate MRI of the brain, pyruvate-to-bicarbonate conversion, representing oxidative metabolism, is detected at low levels, despite the highly oxidative metabolism of the brain. We sought to determine the effect of lactate excitation on bicarbonate detection in healthy rats imaged in a cross-over fashion (lactate flip angle = 90° or 0°). In the brain, the bicarbonate signal-to-noise ratio increased 65 % when lactate was not excited. This effect was not observed in the heart, kidneys or liver. Collectively, our data show that lactate saturation limits bicarbonate detection in the brain solely, which has implications for study designs.

Donghyun Hong¹, Yaewon Kim¹, Chandrasekhar Mushti², Noriaki Minami¹, Anne Marie Gillespie¹, Pavithra Viswanath¹, Rolf E. Swenson², Daniel B. Vigneron ¹, and Sabrina M. Ronen^1
1University of California, San Francisco, San Francisco, CA, United States, ²NHLBI, Bethesda, MD, United States

Mutant IDH leads to 2HG production, which drives glioma development. 13C MRS monitoring of hyperpolarized [1-¹³C]α-ketoglutarate (αKG) metabolism to 2HG and glutamate provides a non-invasive assessment of the IDH mutation and normal metabolism, respectively. However, monitoring 2HG production in vivo is challenging because its resonance is within 0.1 ppm of the natural abundance [5-¹³C]αKG signal of the [1-¹³C]αKG substrate. Here, we utilized [1-¹³C-5-¹²C]αKG, which eliminated the [5-¹³C]αKG peak. This new approach, combined with an optimized sequence, made it possible to readily monitor the production of both 2HG and glutamate in a patient-derived glioma animal model and in normal brain.

Emmanuelle Flatt¹, Bernard Lanz¹, Thanh Phong Lê^1,2, Rolf Gruetter¹, and Mor Mishkovsky^1
1Laboratory for Functional and Metabolic Imaging (LIFMET), EPFL, Lausanne, Switzerland, ²Geneva School of Health Sciences, University of Applied Sciences and Arts Western Switzerland (HES-SO), Geneva, Switzerland

The present work describes a quantitative analysis of lactate ¹³C-labeling pattern following the metabolism of hyperpolarized [²H₇,U-¹³C₆]-D-glucose. This lactate production results from 12 biochemical steps including glucose transport, 10 enzymatic steps of glycolysis, and LDH mediated pyruvate-to-lactate conversion. The 3-compartment model description was found a good compromise to interpret the hyperpolarized metabolic curves. This demonstrates the potential of hyperpolarized [²H₇, U-¹³C₆]-D-glucose as a new biochemical probe for brain energy metabolism.

Viivi Hyppönen¹, Jessica Rosa¹, and Mikko Kettunen^1
1A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland

Anesthesia has profound effects on overall metabolism, leading to significant signal changes in metabolic MR brain experiments using hyperpolarized [1-¹³C]pyruvate. In the current study, we studied the possible origins of the signals from rat liver and heart under isoflurane anesthesia and while the animals were awake. Increased metabolite signals, especially lactate, were observed from both organs in awake animals.

Biranavan Uthayakumar¹, Nadia Bragagnolo², Hany Soliman³, Albert P Chen⁴, Ruby Endre⁵, William J Perks⁶, Nathan Ma⁶, Chris Heyn⁷, Sandra E Black⁸, and Charles H Cunningham^5
1Medical Biophysics, University of Toronto, Mississauga, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Radiation oncolocy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴GE Healthcare, Toronto, ON, Canada, ⁵Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ⁶Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁷Radiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁸Neurology and Hurvitz Brain Sciences Research Program Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

It is well known that glucose is the primary source of energy in the brain, but mounting evidence suggests that at least some of this glucose is first converted to lactate and shuttled between cellular compartments before being oxidized in the TCA cycle. In this study, the hypothesis that this ”lactate shuttle” contributes to the ¹³C-lactate and ¹³C-bicarbonate signal observed in the awake human brain is tested using hyperpolarized ¹³C MRI (HP¹³C-MRI).

Rie Beck Olin¹, Juan Diego Sánchez-Heredia¹, James T Grist^2,3,4,5, Wenjun Wang⁶, Nikolaj Bøgh⁷, Vitaliy Zhurbenko⁶, Esben S Hansen⁷, Rolf F Schulte⁸, Damian Tyler^2,3, Christoffer Laustsen⁷, and Jan Henrik Ardenkjær-Larsen^1
1Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark, ²Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ³Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom, ⁴Department of Radiology, Oxford University Hospitals Trust, Oxford, United Kingdom, ⁵Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom, ⁶Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark, ⁷MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, ⁸GE Healthcare, Munich, Germany

Parallel imaging can aid hyperpolarized ¹³C MRI in extracting more information in the limited time window of the hyperpolarized signal. Using a dedicated, flexible ¹³C receive coil design with coupling coefficients matched for both ¹³C and ²³Na, sensitivity profiles for reconstruction can be acquired at the ²³Na frequency. We demonstrate this method in two hyperpolarized in vivo experiments involving pig kidneys and human brain using a two-times accelerated 3D blipped stack-of-spirals sequence with dual-resolution. The results show good SNR, coverage, and resolution. The method is promising for integrating and automating parallel imaging for hyperpolarized ¹³C MRI.

Rie Beck Olin¹, Tobias Speidel², Juan Diego Sánchez-Heredia¹, Esben S Hansen³, Christoffer Laustsen³, Lars G Hanson^1,4, Volker Rasche⁵, and Jan Henrik Ardenkjær-Larsen^1
1Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark, ²Core Facility Small Animal MRI, University of Ulm, Ulm, Germany, ³MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, ⁴Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark, ⁵Department of Internal Medicine II, University of Ulm, Ulm, Germany

The Seiffert spirals trajectory has favorable properties for hyperpolarized ¹³C MRI. It allows for high degrees of undersampling and combined conjugate gradient compressed sensing SENSE reconstruction when multi-channel arrays are used. The trajectory was evaluated in simulations, in phantom, and for in vivo hyperpolarized ¹³C-urea MRI of pig kidneys with retrospective undersampling and high temporal resolution. For single-frequency imaging, flexible acceleration is achieved through reconstruction based on any number and combination of spiral arms. Simulations demonstrated noise-like aliasing and successful reconstruction. The in vivo experiment showed improved characterization of urea dynamics after undersampling. The reconstruction algorithm can be further improved.

Julia Traechtler¹, Maximilian Fuetterer¹, Tobias Hoh¹, Mohammed Albannay¹, Andreas Dounas¹, and Sebastian Kozerke^1
1University and ETH Zurich, Zurich, Switzerland

In hyperpolarized ¹³C MRI, the achievable base SNR depends on the T₁ relaxation of pyruvate in blood. Heart rate dependency on the resulting SNR is examined using simulations and exemplarily shown on human data of the heart. Measured T₁ and T₂ values at 1.5T and 3T of hyperpolarized ¹³C pyruvate in blood are reported. The results indicate that for a range of pyruvate concentrations, T₂ remains >6s and hence T₂^* is primarily determined by field inhomogeneities. T₁ is reduced at lower concentrations, and therefore heart rate plays a decisive role for the achievable SNR. Exemplary in-vivo data illustrate these findings.

Hikari A. I. Yoshihara¹, Rolf Gruetter¹, and Verena Hoerr^2,3
1LIFMET, EPFL, Lausanne, Switzerland, ²Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany, ³Heart Center, Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany

Ketones bodies are an important metabolic fuel, and butyrate is a ketogenic short-chain fatty acid. We report the metabolism of hyperpolarized (1-¹³C)butyrate in the rat kidney and liver. The main metabolites in the kidney include [1-¹³C]acetoacetate, [1-¹³C]butyrylcarnitine and [5-¹³C]glutamate, and [1-¹³C]acetylcarnitine,  3-hydroxy[1-¹³C]butyrate, [5-¹³C]citrate and [3-¹³C]acetoacetate are also detectable. Fasting results in significantly lower butyrylcarnitine/[1-¹³C]acetoacetate and glutamate/[1-¹³C]acetoacetate ratios. Ketogenesis is observed in the liver and the [1-¹³C]butyrylcarnitine + [1-¹³C]acetoacetate signal normalized to butyrate is higher with fasting. The unexpectedly low 3-hydroxy[1-¹³C]butyrate signals are functional evidence of metabolic zonation, with acetoacetate production and reduction occurring in different cells.

Tobias Speidel¹, Stephan Knecht², Martin Gierse², Tobias Lobmeyer¹, Gordon Winter³, Jessica Löffler³, Maximilian Fellermann⁴, Ilai Schwartz², Holger Barth⁴, and Volker Rasche^1
1Internal Medicine II, Ulm University Medical Center, Ulm, Germany, ²NVision Imaging Technologies GmbH, Ulm, Germany, ³Department of Nuclear Medicine, Ulm University Medical Center, Ulm, Germany, ⁴Institute for Pharmacology and Toxicology, Ulm University Medical Center, Ulm, Germany

Hyperpolarized [1-13C] fumarate has been shown to be a reliable imaging biomarker for monitoring cellular necrosis with conversion of [1-13C]fumarate to [1-13C]malate via Fumarate hydratase. However, the inherently low 13C-sensitivity limits biomedical applications with a need for accessible and low-cost hyperpolarization methods.

In this abstract we show that parahydrogen-induced polarization methods can overcome these limitations by providing highly polarized and purified [1-13C]fumarate as a non-toxic perfusion agent with the capabilities of acting as a biomarker of cell necrosis in metabolic 13C MRI.