Simone Poli^1,2, Ahmed Fahiem Emara³, Edona Ballabani³, Angeline Buser³, Michele Schiavon⁴, David Herzig³, Chiara Dalla Man⁴, Luc Tappy³, Roland Kreis^1,2, and Lia Bally^3
1Magnetic Resonance Methodology, Institute of Diagnostic and Interventional Neuroradiology, University of Bern, Bern, Switzerland, ²Translational Imaging Center, sitem-insel, Bern, Switzerland, ³Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism UDEM, Insel Hospital, University Hospital Bern, Bern, Switzerland, ⁴Department of Information Engineering (DEI), University of Padova, Padova, Italy

The liver takes a central role in the regulation of glucose homeostasis by storing glucose in the fed state and releasing it during food abstinence. As a consequence, the liver is critically involved in glucose homeostasis disorders. We propose a novel non-invasive approach combining Deuterium Metabolic Imaging (DMI) with ¹³C-MRS at 7 T to dynamically map hepatic glucose metabolism. Preliminary results support technical feasibility and provide first insights into distinct hepatic glucose profiles in patients with dysregulated glucose homeostasis. The proposed approach may open new avenues for a better understanding of pathophysiology of glucose dysregulation and development of targeted treatments.

Celine Taglang¹, Georgios Batsios¹, Meryssa Tran¹, Anne-Marie Gillespie¹, Sabrina Ronen¹, and Pavithra Viswanath^1
1Radiology, University of California San Francisco, San Francisco, CA, United States

Elevated choline phospholipid metabolism is a hallmark of cancer. Here, we show that silencing choline kinase a (CKα), the rate-limiting enzyme in choline phospholipid biosynthesis, abrogates total choline (tCho) production from [²H₉]-choline in patient-derived glioma models, indicating that tCho production from [²H₉]-choline predominantly reflects CKα activity. Importantly, we show that [²H₉]-choline metabolism to tCho serves to delineate tumor from normal brain in mice bearing orthotopic patient-derived low-grade gliomas. Furthermore, [²H₉]-choline informs on response to therapy, at early timepoints when anatomical alterations cannot be detected, pointing to the ability of [²H₉]-choline to assess pseudoprogression, which is a challenge in glioma imaging.

Petr Bednarik¹, Dario Goranovic¹, Alena Svatkova², Fabian Niess¹, Lukas Hingerl¹, Bernhard Strasser¹, Dinesh Deelchand³, Benjamin Spurny-Dworak⁴, Siegfried Trattnig¹, Gilbert Hangel^1,5, Thomas Scherer², Rupert Lanzenberger⁴, and Wolfgang Bogner^1
1High Field MR Center, Medical University of Vienna, Vienna, Austria, ²Department of Medicine III, Medical University of Vienna, Vienna, Austria, ³Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ⁴Department of Psychiatry ans Psychotherapy, Medical University of Vienna, Vienna, Austria, ⁵Department of Neurosurgery, Medical University of Vienna, Vienna, Austria

Recent studies have proposed deuterium (²H)-Magnetic Resonance Spectroscopic Imaging (MRSI) as a reliable, non-invasive, and safe method to quantify the human metabolism of ²H-labeled substrates such as glucose and their downstream metabolism and address the major drawbacks of positron emission tomography or carbon (¹³C)-MRS. Here, we pioneered a dynamic proton 3D (¹H)-MRSI for indirect ²H-measurements in humans. In contrast to ²H-MRS(I), the method provides higher sensitivity and chemical specificity to differentiate glutamate, glutamine, and gamma-aminobutyric acid deuterated at specific molecular positions while simultaneously mapping both labeled and unlabeled metabolites without specialized hardware after peroral ingestion of ²H-labeled glucose. 

Lena V. Gast¹, Laura-Marie Baier¹, Oliver Chaudry², Christian R. Meixner¹, Max Müller¹, Klaus Engelke^2,3, Michael Uder¹, Armin M. Nagel^1,4, and Rafael Heiß^1
1Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ²Department of Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ³Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁴Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

In this work, we investigated changes in the tissue potassium and sodium concentrations (TPC/TSC) of calf muscle tissue after exercise and in delayed-onset muscle soreness (DOMS) using combined ³⁹K/²³Na MRI. 14 healthy subjects were examined at baseline, directly after performing eccentric exercises and again 48h after exercise. Sodium and potassium concentrations showed inverse evolution, with changes in TSC being approximately twice as high as in TPC. Moreover, TPC was elevated in sore muscles without obvious edema, while TSC had returned to baseline or below. Thus, combined ³⁹K/²³Na MRI might help to elucidate physiological processes associated with DOMS and muscle fatigue.
 

Kyung Min Nam¹, Ayhan Gursan¹, Nam G. Lee², Jannie Wijnen¹, Dennis Klomp¹, Jeanine Prompers¹, Alex Bhogal¹, and Arjan Hendriks^1
1Radiology, University of Medical Center Utrecht, Utrecht, Netherlands, ²Biomedical Engineering, University of Southern California, Los Angeles, CA, United States

Deuterium metabolic imaging (DMI) is an emerging technique to spatially map metabolism in vivo through the intake of deuterium (i.e., ²H or D) labeled substrates such as [6,6′-²H₂]-glucose. Although DMI has the potential to become a powerful tool to assess liver metabolism, it has limitations due to its long scan time, and low signal-to-noise ratio (SNR) for high spatial resolution in the human body. In this work, we demonstrated the feasibility of low-rank and subspace modeling (LRSM) reconstruction to increase SNR by reducing spectral noise, allowing high spatiotemporal resolution for 3D DMI of the human liver at 7T.

Mohamed Mounir EL MENDILI^1,2, Bertrand AUDOIN^1,2,3, Ben RIDLEY ^1,2, Armin NAGEL⁴, Soraya GHERIB^1,2, Lauriane PINI^1,2, Patrick VIOUT^1,2, Maxime GUYE^1,2, Audrey RICO³, Clemence BOUTIERE³, Jean-Philippe RANJEVA ^1,2, Jean PELLETIER^1,2,3, Adil MAAROUF^1,2,3, and Wafaa ZAARAOUI^1,2
1Aix Marseille Univ, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital de la Timone, CEMEREM, Marseille, France, ³APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France, ⁴University Hospital Erlangen, Institute of Radiology, Erlangen, Germany

Inflammatory demyelinated lesions are a hallmark of multiple sclerosis (MS) and are the pathological substratum of clinical relapses. After their occurrence, neuropathological changes within lesions and lesion repair are variable and unpredictable. Chiefly, recovery from the first relapses is a key element of the long-term prognosis. Thus, in vivo exploration of lesion repair is of paramount importance.

The multi-TE sodium 7T MRI approach revealed that maintained sodium homeostasis within lesion is associated with a better recovery from relapses in MS. Sodium MRI appears to be a promising tool to assess in vivo preservation of neuronal function in MS.

Alixander S Khan^1,2, Joshua D Kaggie^1,2, Mary A McLean^1,2, Rolf F Schulte³, Matthew J Locke¹, Amy Frary¹, and Ferdia A Gallagher^1,2
1Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ²Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, United Kingdom, ³GE Healthcare, Munich, Germany

Deuterium metabolic imaging (DMI) and hyperpolarized ¹³C-pyruvate MRI (HP-¹³C-MRI) are two promising approaches for non-invasive and non-ionizing imaging of tissue metabolism. Here we directly compare these two techniques at 3 T for the first time in humans. DMI using [6,6’-²H₂]glucose, and ¹³C-MRI using hyperpolarized [1-¹³C]pyruvate, were undertaken in five healthy volunteers. The ratio of ¹³C-lactate/¹³C-bicarbonate (mean ±S.D. = 5.05 ±0.89) with HP-¹³C-MRI was higher than the equivalent ²H-lactate/²H-Glx ratio (0.43 ±0.19) with DMI, which can be explained by differences in tracer administration, subsequent timing of acquisition, and tissue physiology. The results demonstrate the two methods provide different yet complementary data. 

Eulalia Seres Roig¹, Henk M. De Feyter¹, Terence Nixon¹, Loreen Ruhm^2,3,4, Nikolai Avdievich², Anke Henning^2,4, and Robin A. de Graaf^1
1Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, ²High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ³IMPRS for Cognitive and Systems Neuroscience, Eberhard-Karls University of Tuebingen, Tuebingen, Germany, ⁴Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

Brain energy metabolism, for which glucose is the main fuel, is essential not only for normal brain function but also for its active role in the mechanisms that underly brain diseases. Deuterium Metabolic Imaging (DMI) is a promising MR modality for investigating whole brain energy metabolism in humans at ultra-high field. In this study, we explore the potential of DMI in the human brain in vivo at 7T. We present whole brain 3D DMI maps of well-resolved deuterated (²H) metabolite resonances of water, glucose and glutamate/glutamine (Glx) following oral administration of [6,6’-²H₂]-labelled glucose.