View Presentation Video

Keywords: Deuterium, Deuterium

DMI is an emerging modality for investigating glucose metabolism in vivo with application for assessing the Warburg effect in tumors.  Although high-field systems, e.g. 7T, provide maximal signal-to-noise ratio (SNR), implementation on widely available 3T scanners could have immediate clinical impact. Here we explore the potential of 3T DMI using a birdcage ²H RF coil in two healthy volunteers and three patients with CNS lesions of varying pathology. Results from these experiments demonstrate the potential to examine the Warburg effect in CNS lesions with DMI at 3T and provide critical data needed to explore DMI SNR and spatial resolution limits.

Narayan Datt Soni¹, Anshuman Swain¹, Paul Jacobs¹, Halvor Juul¹, Ryan Armbruster¹, Ravi Prakash Reddy Nanga¹, Kavindra Nath¹, Corinde Wiers², John Detre³, and Ravinder Reddy^1
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Keywords: Spectroscopy, Deuterium, , 2H-MRS, Brain, TCA, Metabolism

Impaired neurometabolism is often attributed to altered TCA flux (V_TCA). Since, β-hydroxybutyrate metabolism bypasses glycolytic flux, it can be better used to monitor V_TCA. In the current study, [3,4,4,4]-²H₄-β-hydroxybutyrate was infused in 6-month-old mice, and the level of [4,4]-²H_2-Glx was monitored using ²H-MRS. A kinetic model was fitted to determine the rate of BHB metabolism (CMR_BHB) and V_TCA. Glx labeling followed a sigmoidal curve to reach a quasi-steady state concentration (~1.6±0.1 mM) in 30 minutes. CMR_BHB and V_TCA were determined to be 0.054±0.004 and 0.12±0.01 µM/g/min. In conclusion, this method can be used to monitor neurometabolism in health and disease.

View Presentation Video

Fabian Niess¹, Lukas Hingerl¹, Bernhard Strasser¹, Petr Bednarik^2,3, Dario Goranovic¹, Eva Niess¹, Stanislav Motyka¹, Gilbert Hangel^1,4, Martin Krssak⁵, Benjamin Spurny-Dworak⁶, Thomas Scherer⁵, Rupert Lanzenberger⁶, and Wolfgang Bogner^1
1Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria, ²Centre for Functional and Diagnostic Imaging and Research, Danish Research Centre for Magnetic Resonance, Copenhagen, Denmark, ³Department of Radiology, University Hospital Amager and Hvidovre, Copenhagen, Denmark, ⁴Department of Neurosurgery, Medical University of Vienna, Vienna, Austria, ⁵Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria, ⁶Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria

Keywords: Deuterium, Brain

Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are emerging MR techniques to non-invasively map brain glucose uptake and downstream metabolism using safe and affordable deuterium labeled glucose as tracer. This work compares dynamically detected deuterium labeled Glutamate+Glutamine time courses between three-dimensional 3T-¹H QELT-MRSI and 7T-²H-DMI using quantification of concentration estimates. Comparable enrichment of deuterated Glx could be observed in gray matter (1.59±0.24mM vs. 1.39±0.17mM) while differences were found in WM (0.89±0.32 mM vs. 1.31±0.2 mM) presumably due to partial volume contamination. Results showed a successful translation of QELT to clinical 3T. 

View Presentation Video

Keywords: Deuterium, Metabolism

We present an estimation of the minimal dose for D-glucose needed for evaluation of hepatic glucose dynamics by deuterium metabolic imaging (DMI) and investigate whether a subsequent change in hepatic glycogen content is observable by ¹³C-MRS at 7 T. Six healthy subjects received an oral glucose load of 60g, 20g or 10g and were examined with interleaved ²H-MRSI/¹³C-MRS scans for 150 min. Results suggest the feasibility of reducing D-glucose loads to as low as 10g per subject for hepatic DMI with several benefits ‑ including cost, but precision of determination of changes in hepatic glycogen content is substantially reduced.

View Presentation Video

Yanning Liu¹, Zachary Corbin¹, Robert K. Fulbright¹, Terry W. Nixon¹, Scott McIntyre¹, Henk De Feyter¹, and Robin A. de Graaf^1
1Yale University, New Haven, CT, United States

Keywords: Deuterium, Deuterium, DMI

Interleaved MRI-DMI (Deuterium Metabolic Imaging) is a transformative approach to obtain multi-contrast anatomic MRI and metabolic information in parallel with time efficiency. In this work, we expand the toolkit of interleaving ²H DMI with ¹H MRI, by using a newly developed interleaved 3D SWI-DMI sequence that relies on acquiring a truncated ²H signal. Acknowledging the limitations of fitting truncated ²H signals independently, we propose a method to combine truncated FID with fully-sampled acquisitions to improve DMI sensitivity. The updated interleaved MRI-DMI protocol with 3D SWI-DMI was demonstrated on a patient with a brain tumor. 

Xiao-Hong Zhu¹, Wei Zhu¹, Hannes M Wiesner¹, Yudu Li^2,3, Tao Wang¹, Zhi-Pei Liang^2,4, and Wei Chen^1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States

Keywords: Deuterium, fMRI, Functional deuterium metabolic imaging

The relationship of total glucose consumption, TCA cycle and glycolysis in healthy human brain under resting and activated conditions has not been well studied due to the lack of effective neuroimaging tools. The recently developed dynamic deuterium metabolic imaging method provides a long desired capability for such studies. Here, we present the first functional deuterium imaging study in human brains during hemi-field visual stimulation at 7T. Our results provide new insights into the metabolic shifting between oxidative phosphorylation and aerobic glycolysis from the rest to activated state in supporting high energy demand of evoked activity in human visual cortex.

View Presentation Video

Daniel Cocking^1,2, Robin Damion^1,3,4, Elizabeth Simpson³, Paul Greenhaff^3,5,6, Louise Dexter^1,2, Dorothee Auer^1,3,4, and Richard Bowtell^1,2,3
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ²School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ³NIHR Nottingham Biomedical Research Centre/Nottingham Clinical Research Facilities, Queen's Medical Centre, Nottingham, United Kingdom, ⁴Radiological Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁵MRC-Versus Arthritis Centre for Muscoskeletal Ageing Research, University of Nottingham, Nottingham, United Kingdom, ⁶School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

Keywords: Deuterium, Deuterium

We compared the use of DMI following D₂-glucose and D₇-glucose ingestion in the investigation of brain metabolism in vivo.  Multiple CSI measurements were acquired from five participants over ~180 minutes at 7T following ingestion of each labelled compound. D₇-glucose produced significantly larger signals allowing improved mapping of the signals from labelled metabolites.  Calculated time-courses of the changes in metabolite concentration in different brain tissues show significantly larger rates of increase of HDO and Glx in all tissues for D₇- versus D₂­-glucose (e.g. in GM HDO rate of increase for D₇/D₂ = 0.208±0.004/0.051±0.001 mM/min and Glx rate for D₇/D₂ = 0.059±0.003/0.029±0.001 mM/min).

View Presentation Video

Elton Montrazi¹, Dana Peters², Keren Sasson¹, Lilach Agemy¹, Avigdor Scherz¹, and Lucio Frydman^1
1Weizmann, Rehovot, Israel, ²Yale School of Medicine, New Haven, CT, United States

Keywords: Deuterium, Cancer, MRSI

Deuterium metabolic imaging (DMI) is a promising tool for studying tumor metabolism. In DMI [6,6’-²H₂]-glucose is uptaken by tumors, leading to the formation of HDO and of [3,3’-²H₂]-lactate as result of Warburg effect. DMI’s biggest challenge is SNR, consequence of ²H’s low Larmor frequency and the low concentrations of the targets. Depending on the type and size of the tumor, this can bring the key lactate signal below the noise level. This work explores weighted chemical shift imaging (CSI) methodologies for DMI based on SSFP sequences, providing improved lactate sensitivity over recently discussed CSI and multi-echo (ME) SSFP approaches.

View Presentation Video

Xiao Gao¹, Jeremy Gordon², Kai Qiao², Hecong Qin², David Wilson², and Myriam M Chaumeil^2
1Physical Therapy, UCSF, San Francisco, CA, United States, ²UCSF, San Francisco, CA, United States

Keywords: Deuterium, Alzheimer's Disease

We performed a deuterium metabolic imaging (DMI) investigation of two deuterated probes with different metabolic properties: 1) the glucose analog [2,2’-²H₂]-deoxy-D-glucose ([²H₂]2DG) which gets intracellularly trapped after being phosphorylated by hexokinase; and 2) [6,6′-²H₂]-D-glucose ([²H₂]Glc) which undergoes full oxidative catabolism. We tested their potential to detect metabolic impairment in a mouse model of Alzheimer’s disease. Our results demonstrated that the accumulation / metabolism of these two glucose derivatives can be detected dynamically in the mouse brain, and that DMI can detect disrupted glucose metabolism in an AD model.

View Presentation Video

Celine Taglang¹, Georgios Batsios¹, Anne-Marie Gillespie¹, and Pavithra Viswanath^1
1Radiology and Biomedical imaging, University of California San Francisco, San Francisco, CA, United States

Keywords: Deuterium, Cancer

Aberrant choline phospholipid biosynthesis is a metabolic hallmark of cancer. Choline kinase α (CKα) is the key enzyme in this pathway. Non-invasive methods of imaging CKα have the potential to report on tumor proliferation. Here, using a combination of RNA interference and doxycycline-inducible gene silencing systems, we show that deuterium magnetic resonance spectroscopy following administration of [²H₉]-choline non-invasively reports on CKα activity in patient-derived glioma cells and intracranial tumors. Importantly, [²H₉]-choline provides an early readout of response to chemotherapy in mice bearing intracranial gliomas. Our studies identify a novel agent for metabolic imaging of gliomas and their response to therapy.

View Presentation Video

Friederike Hesse^1,2, Flaviu Bulat^1,3, Felix Kreis¹, and Kevin M. Brindle^1,4
1CRUK CI, University of Cambridge, Cambridge, United Kingdom, ²Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ³Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, ⁴Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

Keywords: Deuterium, Molecular Imaging

²H MRI measurements of labeled malate production following intravenous injection of ²H-labeled fumarate (1 g/kg) have been used to detect tumor cell death post-treatment in pre-clinical tumor models. We show here that much lower concentrations of ²H-labeled fumarate (0.1, 0.3 and 0.5 g/kg) can still generate a significant increase in malate concentration post-treatment, which should facilitate clinical translation. Mice were implanted subcutaneously with a triple-negative breast cancer model (MDA-MB-231) and treated with three different concentrations of a TRAIL-R2 agonist (MEDI3039). The different degrees of cell death obtained were linearly correlated with the malate/fumarate signal ratio and the absolute malate concentration. 

View Presentation Video

Christian Licht¹, Jascha Zapp¹, Mark Bydder², Maxime Guye², Lothar R. Schad¹, and Stanislas Rapacchi^2
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²CRMBM, Aix-Marseille Université, Marseille, France

Keywords: Non-Proton, Multi-Contrast, Sodium

Sodium (²³Na) MRI has received increased attention as a potential biomarker for disease states thanks to the advent of high and ultra-high field MRI. One asset from ²³Na MRI is the distinction between single and triple quantum signal to provide new insights in tissue characterization. Hence, efficient sequences are needed that enable simultaneous ²³Na and ²³Na multi-quantum-coherences imaging to fully exploit the signal's potential. Therefore, we propose a new sequence utilizing a double-half-echo ²³Na readout. Additionally, we propose to exploit this image further to drive the reconstruction of the low resolution MQC images.

View Presentation Video

Samuel Rot^1,2, Jon O Cleary³, Ayse Sila Dokumaci^4,5, Michael Eyre^4,5,6, Philippa Bridgen^5,7, Yasmin Blunck^8,9, Warda Syeda¹⁰, Shaihan J Malik^4,5, Joseph V Hajnal^4,5, Bhavana S Solanky^1,11, Shan-Shan Tang⁶, Claudia AM Gandini Wheeler-Kingshott^1,12,13, and David Carmichael^4,5
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, ²Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ³Department of Radiology, Imperial College Healthcare NHS Trust, London, United Kingdom, ⁴Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom, ⁵London Collaborative Ultra high field System (LoCUS), London, United Kingdom, ⁶Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, ⁷Guys and St Thomas’ NHS Foundation Trust, King's College London, London, United Kingdom, ⁸Department of Biomedical Engineering, The University of Melbourne, Melbourne, Australia, ⁹Melbourne Brain Imaging Unit, The University of Melbourne, Melbourne, Australia, ¹⁰Melbourne Neuropsychiatry Centre, The University of Melbourne, Parkville, Victoria, Australia, ¹¹Quantitative Imaging Group, Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ¹²Department of Brain & Behavioural Sciences, University of Pavia, Pavia, Italy, ¹³Brain Connectivity Centre Research Department, IRCCS Mondino Foundation, Pavia, Italy

Keywords: Non-Proton, Relaxometry, Sodium, T2* mapping

In vivo ²³Na-MRI benefits greatly from SNR improvements at ultrahigh fields and with multi-channel receivers. Here, we report a pipeline for multi-echo radial imaging of ²³Na (MERINA)  at 7T, using a 32-channel receiver coil. This involves correction of image artifacts induced by gradient imperfections, followed by channel combination to maintain Rician noise distributions in combined magnitude images. This led to improved T₂* mapping with a fixed-component bi-exponential signal model. T₂* values (e.g. T_2s*=4.6±0.9ms, T_2l*=28.3±2.8ms in cerebral white matter) agree with reports in literature. Future work will involve correcting B₀ inhomogeneity effects, more sophisticated signal models and exploring potential clinical applications.

View Presentation Video

Vanessa L. Franke^1,2, Johannes S. Breitling¹, Renate Bangert¹, Philip S. Boyd¹, Nina Weckesser³, Heinz-Peter Schlemmer^3,4, Daniel Paech^3,5, Mark E. Ladd^1,2,4, Peter Bachert^1,2, and Andreas Korzowski^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ³Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Faculty of Medicine, University of Heidelberg, Heidelberg, Germany, ⁵Division of Neuroradiology, University Hospital Bonn, Bonn, Germany

Keywords: Spectroscopy, Non-Proton, 31P, phosphorus, pH

³¹P MRSI enables non-invasive mapping of pH value and magnesium content in vivo, and is conventionally done by calibration equations, like the modified Henderson-Hasselbalch equation, relating ³¹P chemical shifts to physiological parameters. The reliability of this approach might be hampered when applied to diseased tissue, like cancer, where the chemical conditions are altered. Recently, we proposed a chemical shift dictionary for ³¹P MRSI to potentially enable a condition-independent estimation of pH value and magnesium content. In this study, the applicability of this approach to in vivo data is tested, and its potential for further research identified.

View Presentation Video

Lieke van den Wildenberg¹, Ayhan Gursan¹, Leonard Seelen¹, Tijl van der Velden¹, Mark Gosselink¹, Martijn Froeling¹, Wybe van der Kemp¹, Dennis Klomp¹, and Jeanine Prompers^1
1Center for Image Sciences, University Medical Center Utrecht, Utrecht, Netherlands

Keywords: Liver, Spectroscopy

³¹P MRS can be used in liver disease diagnosis and treatment monitoring. However, it is unclear whether ³¹P metabolite concentrations differ across the healthy liver, which would be important to take into account. Using an integrated ³¹P whole-body transmit coil for a 7T MRI scanner in combination with a 16-channel body receive array, we aimed to assess spatial variations of ³¹P metabolites within the liver in healthy subjects. We showed that there is significant spatial heterogeneity of various ³¹P metabolites levels within the liver, with marked differences for the PME and PDE metabolites between the left and right lobe.