Cristina Cudalbu¹, Katarzyna Pierzchala^1,2,3, Dunja Simicic^1,2, Graham Knott⁴, Stephanie Clerc-Rosset⁴, Bernard Lanz², and Ileana Jelescu^1
1Centre d'Imagerie Biomedicale, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Laboratory for functional and metabolic imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland, ⁴Biological Electron Microscopy Facility, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

In chronic hepatic encephalopathy (HE), high ammonium delivery to the brain is causing the accumulation of glutamine (Gln) and gradual release of other osmolytes. We aimed to follow the longitudinal evolution of brain Gln and other metabolite properties in chronic-HE using diffusion-weighted spectroscopy (DW-MRS) and evaluate the potential changes in diffusion behavior which might provide information on Gln localization and potential microstructural alterations during chronic-HE. Increased diffusivity and reduced kurtosis in BDL rats, showcased by DW-MRS analysis, are fully consistent with a less complex microstructure and swollen soma as highlighted by fluorescence and electron microscopy leading to increased molecule mobility.

Tianxiao Zhang¹, Tianyao Wang², Zengping Lin¹, Rong Guo^3,4, Yudu Li^3,4, Yibo Zhao^3,4, Ziyu Meng^1,3, Jun Liu², Danhong Wu⁵, Zheng Jin⁶, Xin Yu⁷, Zhi-Pei Liang^3,4, and Yao Li^1
1Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Radiology Department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, 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, ⁵Neurology Department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China, ⁶Shanghai Minhang Hospital of Integrated Traditional Chinese and Western Medicine Hospital, Shanghai, China, ⁷Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Mapping the concurrent changes in oxygen extraction fraction (OEF) and neurometabolic markers could provide a powerful tool for evaluation of brain tissue viability after stroke. In this work, we investigated the feasibility of fast simultaneous 3D brain OEF and neurometabolic imaging noninvasively in acute ischemic stroke using SPICE. We achieved concurrent mapping of OEF (1.2×1.2×1.2 mm³ nominal resolution) and MRSI (2.0×3.0×3.0 mm³ nominal resolution) within a 7-minute scan. Our experimental results demonstrated the feasibility of mapping OEF and neurometabolic alterations in acute stroke.

Dikoma C. Shungu¹, Xiangling Mao¹, Michelle Blate², Diana Vu², Guoxin Kang¹, Halinder S. Mangat³, Claire Henchcliffe³, Bejamin Natelson², and Nora Weiduschat^1
1Radiology, Weill Cornell Medicine, New York, NY, United States, ²Icahn School of Medicine at Mount Sinai, New York, NY, United States, ³Neurology, Weill Cornell Medicine, New York, NY, United States

N-acetylcysteine (NAC), a glutathione (GSH) synthesis precursor, is thought to have anti-glutamatergic properties for which direct in vivo evidence is lacking. In this study, the postulated anti-glutamatergic properties of NAC were investigated by using ¹H MRS to monitor changes in brain levels of both GSH and glutamate (Glu) in response to 4 weeks of NAC supplementation in patients with chronic fatigue syndrome (CFS) and healthy volunteers (HV). Following NAC treatment, GSH levels increased significantly in CFS and numerically in HV, while Glu decreased significantly in both groups compared to baseline – a finding that supports NAC as an anti-glutamatergic agent.

Petr Bednarik¹, Lukas Hingerl¹, Dario Goranovic¹, Alena Svatkova¹, Pedro de Lima Cardoso¹, Siegfried Trattnig¹, Rupert Lanzenberger², and Wolfgang Bogner^1
1Department of Medical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

Functional single-voxel MRS (fMRS) was capable to sensitively detect metabolite responses to sensory stimulation, but suffered from large partial volume effects, that questioned the clinical utility of fMRS. Free-induction decay (FID)-MRSI promises to possess sufficient SNR to reach the sensitivity of SV-MRS and overcome its limitations by selective mapping the volume of interest with multiple voxels and thus, with higher spatial resolution, minimize the partial volume issue.  Concentric-ring-trajectories (CRT)-based 3D FID-MRSI showed sufficient sensitivity and temporal stability to detect functional glutamate changes in the dominant sensorimotor region with expected most robust metabolite responses during finger tapping task.

Hannah J. Lees¹, Micaela Millan¹, Fayyaz Ahamed², Roozbeh Eskandari¹, Kristin L. Granlund¹, Sangmoo Jeong¹, and Kayvan R. Keshari^1
1Memorial Sloan Kettering Cancer Center, NEW YORK, NY, United States, ²University of California, Berkeley, Berkeley, CA, United States

The pyruvate-lactate flux, k_PL, shows promise as a biomarker of cancer presence and aggressiveness, and assessment of k_PL in patient-derived cells may be a useful tool to assess treatment response for advanced personalized medicine. Here we present a novel experimental protocol for the real-time measurement of pyruvate-lactate metabolic flux in multiple mass-limited cell suspension samples using a single dissolution, thereby increasing efficiency and providing greater control of the methodological variability associated with HP experiments. We then applied this protocol to the measurement of pyruvate-lactate flux in melanoma cells for the assessment of treatment response to BRAF inhibition.

Yao Li¹, Zengping Lin¹, Tianyao Wang², Tianxiao Zhang¹, Rong Guo^3,4, Yudu Li^3,4, Yibo Zhao^3,4, Ziyu Meng^1,3, Jun Liu², Xin Yu⁵, and Zhi-Pei Liang^3,4
1Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Radiology Department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, 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, ⁵Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Impaired metabolism was a key factor in the definition of ischemic penumbra. ¹H-MRSI has been recognized as a potentially powerful tool for metabolic imaging of stroke. In this proof of concept clinical study, we explored the potential of fast 3D high-resolution ¹H-MRSI to investigate brain neurometabolic changes at tissue-level in acute stroke. In a 6-min scan, we obtained N-acetylaspartate (NAA) and lactate (Lac) maps simultaneously. Our experimental results showed different NAA and Lac concentrations between hypoperfused tissue recruited to final infarct and that survived, indicating an improved delineation of penumbra by incorporating the tissue neuronal damage and acidosis information.

Shizhe Li¹, Li An¹, Christopher Johnson¹, Maria Ferraris-Araneta¹, Milalynn Victorino¹, Jyoti Tomar¹, and Jun Shen^1
1National Institutes of Health, Bethesda, MD, United States

This study demonstrates the feasibility of detecting carbonic anhydrase activity in the frontal lobe of the human brain. Upon saturation of carbon dioxide, a very large magnetization transfer effect catalyzed by carbonic anhydrase was measured in the frontal lobe of healthy human subjects using ¹³C MRS with oral administration of [U-¹³C₆]glucose. The results showed that it is feasible to examine carbonic anhydrase activity using magnetization transfer ¹³C MRS in the frontal cortex—where structural lesions, disturbed function, and morphology are strongly associated with many psychiatric symptoms.

Neda Gholizadeh¹, Peter B Greer^2,3, John Simpson^2,3, Jonathan Goodwin^2,3, Peter Lau^4,5, Arend Heerschap⁶, and Saadallah Ramadan^1,5
1Health Science, The University of Newcastle, Newcastle, Australia, ²Radiation Oncology, Calvary Mater Newcastle, Newcastle, Australia, ³Physics and mathematics, The University of Newcastle, Newcastle, Australia, ⁴Radiology, Calvary Mater Newcastle, Newcastle, Australia, ⁵Imaging Centre, Hunter Medical Research Institute (HMRI), Newcastle, Australia, ⁶Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Nijmegen, Netherlands

Due to histological heterogeneity of the central gland, accurate detection of central gland prostate cancer remains a challenge. A reliable and non-invasive imaging technique could increase the sensitivity and specificity for identification of central gland lesions missed by PI-RADS V2 or biopsies.  This study evaluates the diagnostic performance of individual and combined parameters of an mp-MRI exam, employed for PI-RADS evaluations (T2WI, DWI, DCE) and advanced GOIA-sLASER MRSI using an external phased-array coil for central gland prostate cancer detection, localization and grading. The results demonstrate that MRSI using GOIA-sLASER considerably improves central gland prostate cancer detection and localization.

Adil Bashir¹, Jianyi Zhang², and Thomas S Denney ^1
1Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, United States

Long TR and low concentration makes the quantification of inorganic phosphate (Pi) difficult in 31P magnetization saturation transfer experiments. An indirect method to measure Adenosine Triphosphate (ATP) turnover was demonstrated in animal studies, which does not require quantification of Pi. We demonstrate the application and validation of this technique in human studies. We measured the fluxes of ATP production and hydrolysis reactions using the indirect approach and validated the results against direct measurements. We also report the intrinsic T1 of Phosphocreatine, ATP and Pi in skeletal muscle at 7T. This will facilitate future studies of impaired bioenergetics in vivo.

Josephine L Tan^1,2, Daniel Djayakarsana^1,2, Rachel W Chan², Colleen Bailey^1,2, and Angus Z Lau^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

Deuterium (²H) magnetic resonance spectroscopy (MRS) is a novel metabolic imaging method that can measure aberrant glucose metabolism in cancer. In this abstract, we use ²H MRS to measure metabolic changes in acute myeloid leukemia (AML) cells after treatment with cisplatin. We show that this method is sensitive to differences in lactate levels, produced via glycolysis of deuterium-enriched glucose at 7T. These studies demonstrate the potential of ²H MRS to monitor chemotherapeutic response.