Robin Damion^1,2,3, Daniel Cocking^3,4, Hester Franks¹, Daniel Wilkinson^5,6, Matthew Brook^2,6,7, Dorothee Auer^1,2,3, and Richard Bowtell^2,3,4
1School of Medicine, University of Nottingham, Nottingham, United Kingdom, ²NIHR Nottingham Biomedical Research Centre/Nottingham Clinical Research Facilities, University of Nottingham, Nottingham, United Kingdom, ³Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ⁴School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom, ⁵Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Nottingham, United Kingdom, ⁶MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham, United Kingdom, ⁷School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

Double-quantum filtered (DQF) deuterium spectra were obtained on a 3T scanner from lower leg and forearm muscles of volunteers whose deuterium abundance was increased by approximately 100 times through ingestion of deuterium oxide. Quadrupolar splitting frequencies of approximately 20 – 40 Hz were measured throughout the various muscle groups of the lower leg, with some regions showing little or no splitting. Although the DQF sequence considerably reduces the signal intensity, it has the advantage that it removes any isotropic signal component and therefore reveals an anisotropic component that might have been obscured.

Philip M. Adamson¹, Keshav Datta², Ron Watkins², Lawrence Recht³, Ralph Hurd², and Daniel Spielman^2
1Department of Electrical Engineering, Stanford University, Palo Alto, CA, United States, ²Department of Radiology, Stanford University, Palo Alto, CA, United States, ³Department of Neurology, Stanford University, Palo Alto, CA, United States

Deuterium metabolic imaging (DMI) is an emerging modality for investigating glucose metabolism with particular 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.   Using a birdcage ²H RF coil, modified gradient filter, and spherical k-space sampling, we demonstrate high-quality 3T whole-brain DMI of healthy adults following the oral ingestion of deuterated glucose. Results from these experiments provide critical data needed to explore DMI SNR, spatial resolution, and imaging time tradeoffs.

Daniel Cocking^1,2, Robin Damion^2,3,4, Hester Franks⁵, Daniel Wilkinson^6,7, Matthew Brook^4,6,8, Dorothee Auer^2,3,4, and Richard Bowtell^1,2,4
1School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ²Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ³Mental Health and Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁴NIHR Nottingham Biomedical Research Centre/Nottingham Clinical Research Facilities, Queen's Medical Centre, Nottingham, United Kingdom, ⁵Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁶MRC-Versus Arthritis Centre for Musculosketal Ageing Research, University of Nottingham, Nottingham, United Kingdom, ⁷Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁸School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

Deuterium magnetic resonance measurements are of growing interest in the field of metabolic imaging. Four subjects were loaded with D₂O to ~1.5% enrichment over a 6-week period for a parallel study of immune cell proteomics. We report T₁ and T₂^* relaxation times of deuterium in HDO measured from cerebral spinal fluid (CSF), white matter (WM) and grey matter (GM) in vivo, using a 7T Philips Achieva scanner with a dual-tuned ²H/¹H birdcage coil. ²H T₁ values are significantly shorter than corresponding values for ¹H in H₂O, due to the quadrupolar ²H relaxation, whilst T₂* values are comparable to ¹H values.

Elton Tadeu Montrazi¹, Qingjia Bao², Dana Peters³, Keren Sasson¹, Lilach Agemy¹, Avigdor Scherz¹, and Lucio Frydman^1
1Weizmann Institute of Science, Rehovot, Israel, ²Chinese Academy of Sciences, Wuhan, China, ³Yale School of Medicine, New Haven, CT, United States

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of cancers. We recently showed that deuterium metabolic imaging (DMI) can serve as a potential method for PDAC’s detection; we also demonstrated that multi-echo balanced steady-state free precession (ME-bSSFP) can greatly increase DMI’s SNR per unit time compared to CSI acquisitions. This study synergizes these aspects, to provide high resolution maps on the metabolic kinetic of PDAC and pancreatitis mouse models.  ME-bSSFP at 15.2T showed that lactate accumulated in different kinds of tumors. In general, glucose was also uptaken by the tumors, and HDO concentrated in them.

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

²H-MRS is a novel method of imaging flux through metabolic pathways. Here, we show that ²H-MRS can be used to probe the isocitrate dehydrogenase 1 mutation (IDHmut), which catalyzes production of the oncometabolite 2-hydroxyglutarate (2-HG) in low-grade gliomas. Our results indicate that 2-HG production from [3,3’-²H]-α-KG can be specifically observed in IDHmut cells. Importantly, treatment with an IDHmut inhibitor, which is in clinical trials for low-grade glioma patients, results in a significant reduction in 2-HG production from [3,3’-²H]-α-KG in IDHmut cells. Our results point to the potential of [3,3’-²H]-α-KG as a probe of glioma IDHmut status and response to therapy.

Neil Wilson¹, Abigail Cember¹, Laurie Rich¹, Puneet Bagga², Ravi PR Nanga¹, Sophia Swago³, Deepa Thakuri¹, Mark Elliott¹, Mitchell Schnall¹, John Detre⁴, and Ravinder Reddy^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN, United States, ³Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, ⁴Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

Deuterium metabolic imaging (DMI) has brought about a renewed interest in the application of ²H-labeled substrates to map metabolism in vivo, yet deuterium spectroscopy remains challenging. We have shown that metabolism of deuterium-labeled glucose can be observed in the proton spectrum through a reduction in signal of downstream metabolites in a technique called quantitative exchange label turnover MRS (qMRS). Here, we show that prior knowledge fitting that includes unlabeled as well as deuterium-labeled forms of glutamate can be used to map neural metabolism reliably with qMRS.

 

Michael Vaeggemose^1,2, Rolf F. Schulte³, Christoffer Laustsen², Esben Søvsø Szocska Hansen², and Nikolaj Bøgh^2
1GE Healtcare, Broendby, Denmark, ²MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark, ³GE Healtcare, Munich, Germany

Deuterium metabolic imaging (DMI) has emerged as a novel biomarker comparable to ¹⁸FDG PET by adding quantitative metabolic kinetic capabilities at high field (>3T). The main barrier for widespread clinical adoption, is the availability of high field clinical scanners. The aim of this study is to determine if DMI for neurological applications is feasible on a clinical 3T MRI scanner. Our findings suggests that it is indeed feasible, and that metabolic breakdown product (Glutamine/Glutamate) can be quantified around 120 min after ingestion.

Daniel Cocking^1,2, Robin Damion^2,3,4, Hester Franks⁵, Daniel Wilkinson^6,7, Dorothee Auer^2,3,4, Matthew Brook^4,6,8, and Richard Bowtell^1,2,4
1School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ²Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ³Mental Health and Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁴NIHR Nottingham Biomedical Research Centre/Nottingham Clinical Research Facilities, Queen's Medical Centre, Nottingham, United Kingdom, ⁵Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁶MRC-Versus Arthritis Centre for Musculosketal Ageing Research, University of Nottingham, Nottingham, United Kingdom, ⁷Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁸School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

Deuterium magnetic resonance imaging and spectroscopy at 7T has been used to follow the deuterium concentration in the brain over an ~eight-hour period while subjects orally-loaded with D₂O to 100x natural abundance. Changes in deuterium concentration of ~ 0.1% can be readily monitored in ²H spectra acquired in 1 minute and images acquired in 7.5 minutes. The change in deuterium concentration estimated from ²H spectra is in agreement with the value calculated from cumulative D₂O dose and body mass and the signal changes measured from ROIs in the brain have similar time-courses, with relative signal strengths dictated by T₂*-weighting.

Minghao Zhang¹, Jabrane Karkouri¹, Daniel Atkinson¹, Brandon Tramm², Scott Schillak², and Christopher T. Rodgers^1
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, ²Virtumed LLC, Minneapolis, MN, United States

Deuterium metabolic imaging (DMI) has been proposed as a means to probe glucose uptake and metabolism. It is expected that DMI will reveal important changes in cancer and neurodegeneration. We constructed a dual-tuned 7T ²H/¹H array coil and assessed appropriate RF power limits by EM modelling. The coil performance has been assessed with phantom scans on a D₂O-enriched agar phantom. We are now ready to start human in vivo scanning.

Xiao Gao^1,2,3, Jeremy Gordon², Kai Qiao², Ilona Polvoy², Tanner Nickles^2,3, David Wilson², and Myriam M. Chaumeil^1,2,3
11 Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ³UC Berkeley-UCSF Bioengineering Program, University of California, San Francisco, San Francisco, CA, United States

2-deoxy-d-glucose (2-DG) is a glucose analog widely used in FDG-PET imaging as a biological tracer of glucose uptake. This study innovatively redirects its application in ²H NMR by using a deuterated version of 2-DG (2-DG-d2) and explores its imaging potential in mapping glucose uptake without ionizing radiation. A workflow is described here regarding multi-band RF pulse design and bSSFP sequence optimization, which enables a rapid ²H imaging with high sensitivity. Both in vitro and in vivo imaging results have validated the pulse sequence’s specificity and sensitivity of detecting 2-DG-d2 with high spatial resolution, inspiring its further implementation in the future.

Ying Xiao^1,2, Daniel Wenz¹, and Lijing Xin^1
1Animal imaging and technology (CIBM), EPFL, Lausanne, Switzerland, ²Laboratory for Functional and Metabolic Imaging (LIFMET), EPFL, Lausanne, Switzerland

¹H-[¹³C] NMR spectroscopy is a powerful tool to study metabolic information in human brain. At 7T, the proton-observed carbon-edited (POCE) method provides high sensitivity and improved spectral resolution. However, the application in human brain has more constraints due to high RF power deposition at 7T. In this study, we investigated the performance of the STEAM-based POCE sequence without decoupling to reduce the RF power. The phantom experiments and the Monte Carlo simulations demonstrated high-quality ¹H-[¹³C] MR spectra and the accurate quantification of ¹³C-labeled glutamate and glutamine without decoupling at 7T.

Lawrence Michael Lechuga¹, Paul Begovatz², Bruce D Collick³, and Sean B Fain^4
1Medical physics, University of Wisconsin Madison, Madison, WI, United States, ²Medical Physics, University of Wisconsin, Madison, Madison, WI, United States, ³Radiology, University of Wisconsin, Madison, Madison, WI, United States, ⁴Radiology, University of Iowa, Iowa City, WI, United States

The focus of this work is on the optimization of fluorine-19 enabled SPGR, bSSFP, and phase cycled bSSFP (bSSFP-C) pulse sequence parameters to improve signal acquisition efficiency for perfluoropolyether (PFPE) at 3T with a multi-channel coil. Bloch simulations and subsequent experimental validation were performed to determine the parameters to maximize the SNR-efficiency for each sequence. Acquisitions of the optimized SPGR, bSSFP, and bSSFP-C were then assessed for their achieved SNR-efficiency. bSSFP and bSSFP-C demonstrated increased sensitivity compared to SPGR. Feasibility of bSSFP-C with parallel imaging demonstrated the ability to reduce scan times by 2-fold without compromising the qualitative image quality. 

Alex Ensworth^1,2, Cariad-Arianna Knight¹, Piotr Kozlowski^1,2,3,4, Cornelia Laule^1,2,3,5, Alex L. MacKay^1,3,4, and Carl A. Michal^1
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada, ⁴UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ⁵Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Phosphorus (³¹P) nuclear magnetic resonance spectroscopy (NMR) has the potential to play a valuable role in the characterization of myelin due to the concentration of ³¹P present in myelin phospholipids. This study demonstrates the feasibility of detecting ³¹P through cross polarization (CP) and magnetization transfer (MT) from hydrogen in preserved murine spinal cord and fresh porcine brain. The results demonstrate the detection of myelin phospholipids through these NMR techniques and provide compelling proof of concept for the potential applicability of MT-CP in ³¹P MRI for non-ambiguous myelin characterization in vivo.

Vanessa L. Franke^1,2, Johannes Breitling¹, Renate Bangert¹, Mark E. Ladd^1,2,3, 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, ³Faculty of Medicine, University of Heidelberg, Heidelberg, Germany

The determination of tissue pH under varying cellular conditions by means of ³¹P MRS is challenging. We propose a concept for a dictionary-based approach for pH estimation under different chemical conditions. As proof-of-concept, we demonstrate its feasibility for a limited subset of conditions using the chemical shifts of ATP and their dependence on pH and magnesium. For the presented subset, the estimated pH values are in good agreement with the prepared values. However, for application to in vivo data, an extension of the dictionary to include other influences, e.g. of other ions, is required and the subject of ongoing work.

Rolf Pohmann¹ and Klaus Scheffler^1,2
1Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ²Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany

Even after a large number of studies with varying outcome, the effect of brain activation on the ³¹P spectrum is still unclear. Here, the SNR gain expected from a field strength of 9.4 T is used to determine changes in the metabolite peaks during a 5 min stimulus. In spite of the high SNR and spectral quality, no significant variations were found. Especially the amplitude and linewidth of the PCr-peak did not change, and, while the signal of extracellular inorganic phosphate was well visible after averaging over all subjects, no variations in its amplitude or position were observed.

Jan-Ruediger Schuere¹, Eike Steidl¹, Elisabeth Neuhaus², Manoj Shrestha³, Elke Hattingen¹, and Ulrich Pilatus^1
1Neuroradiology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany, ²Goethe University Hospital Frankfurt, Frankfurt am Main, Germany, ³Brain Imaging Center, Goethe University, Frankfurt am Main, Germany

In this work, APT-CEST imaging in combination with 1H and 31P spectroscopy was performed to investigate 17 patients with different brain tumors. A synergistic analysis should help for a better understanding of the APT-CEST contrasts such as MTRasym with regard to tumor metabolism and further physiological relationships such as the pH-sensitivity.