Rong Guo^1,2, Yibo Zhao^1,2, Yudu Li^1,2, Pallab Bhattacharyya³, Mark Lowe³, Hannes M. Wiesner ⁴, Yao Li⁵, Xiao-Hong Zhu⁴, Wei Chen⁴, and Zhi-Pei Liang^1,2
1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ⁴Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ⁵School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

Ultrahigh field systems provide significant SNR benefits to MRSI, but also bring new challenges for accelerated MRSI due to increased spectral bandwidth and larger B₀/B₁ inhomogeneities. We have managed to overcome these problems and developed a SPICE-based data acquisition and processing technique for rapid, high-resolution spectroscopic imaging of the human brain without water-suppression at 7T. The proposed method can simultaneously obtain metabolite signals at 3.0×3.0×3.0 mm³ resolution and companion water signals at 1.0×1.0×3.0 mm³ resolution with high SNR in a single 8 min scan.

Tao Gong¹, Yufan Chen¹, Liangjie Lin², Youting Lin³, and Guangbin Wang^1
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, ²Philips Healthcare, Beijing, China, ³Departments of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

The aim of this study was to investigate the metabolic dysfunction of FCD associated epilepsy using Edited MRS. 14 patients and 14 age- and sex-matched healthy controls underwent MR scans, including Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). The results indicated that GABA levels were significantly increased in epilepsy focal region of patients compared with contralateral regions and healthy controls, while no significant alterations were found in GSH and Glx levels. GABAergic inhibition enhances in FCD foci suggested that GABA may play a central role in the pathophysiology of FCD associated epilepsy.

Lihong Tang¹, Hui Huang¹, Miao Zhang², Yibo Zhao^3,4, Rong Guo^3,4, Yudu Li^3,4, Zhi-Pei Liang^3,4, Wei Liu⁵, Yao Li¹, Biao Li², and Jie Luo^1
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³Department of Electrical and Computer Engineering, University of Illinois at Urbana Champaign, Urbana, IL, United States, ⁴Beckman Institute for Advanced Sciences and Technology, University of Illinois at Urbana Champaign, Urbana, IL, United States, ⁵Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

NAA decrease and FDG low uptake in cortical and subcortical regions of the limbic system are among the most common findings in temporal lobe epilepsy (TLE) patients. In addition, tissue susceptibility changes in the deep nuclei, myelin water fraction and NAA decrease in white matter bundles might offer complementary information for lateralization. We demonstrated the feasibility of simultaneous high-resolution 1H-MRSI (2.0 x 3.0 x 3.0 mm³), MWF, QSM, and ¹⁸F-FDG-PET and investigated potential of the multimodal information for detecting metabolic and microstructural changes in subcortical, cortical and white matter regions for TLE, with results consistent with literature for each modality.

Lei Wang¹, Longxiao Wei¹, and Menghui Yuan^1
1Nuclear Medicine, Tangdu Hospital of Air Force Medical University, Xi'an, China

The commonly used granger causality (GC) and the metabolic effective connection (MEC) methods, had been compared the efficacy in identifying the directional pathways of dopamine system on the base of simultaneous PET/MR data. GC and MEC both identified different directed pathways of dopamine system. GC identified more long pathways from cortex to nucleus than MEC, while MEC did better job in identifying subtentorial pathways. The unidirectional frontostriatal pathways identified by MEC was more inline with existing researches than GC, the latter reported bidirectional interaction pathways there. MEC was recommended in region-wise research when PET/MR is available.

Jialin Hu¹, Miao Zhang², Yaoyu Zhang¹, Rong Guo^3,4, Yudu Li^3,4, Yibo Zhao^3,4, Ziyu Meng¹, Biao Li², Jun Liu⁵, Binyin Li⁵, Jie Luo¹, Chao Ma⁶, Georges El Fakhri⁶, Zhi-Pei Liang^3,4, and Yao Li^1
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 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 Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁶Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

Beta-amyloid (Aβ) aggregation and neurometabolic changes are biomarkers for Alzheimer’s disease (AD) at early stage. But their underlying relationship in association with AD pathology is still not fully understood. In this study, we simultaneously acquired 3D high-resolution MRSI using SPICE and ¹⁸F-AV45-PET images on a PET-MR scanner. Concurrent changes in neurometabolite concentrations and Aβ deposition in healthy control, mild cognitive impairment, and AD groups were compared. An increase in myo-inositol and a decrease in N-acetylaspartate were found as dementia became more severe. Our findings may lay a foundation for further investigation of AD pathogenesis using multimodal metabolic imaging.

Rui Vasco Simoes¹, Rafael N Henriques¹, Beatriz M Cardoso¹, Francisca F Fernandes¹, Jonas L Olesen², Sune N Jespersen², and Noam Shemesh^1
1Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal, ²Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Glioblastoma multiforme has been reported to rely both on glycolysis and oxidative metabolism but methods are lacking to assess such heterogenity in vivo. We previously showed a novel application of Marchenko–Pastur PCA denoising (MP-PCA) to dynamic glucose-enhanced deuterium MRS (DGE ²H-MRS). Here, we use this approach to measure glycolytic and oxidative metabolic turnover rates in mouse glioma, thereby assessing their functional metabolic heterogeneity. This methodology can be extended to other cancer models and is available for clinical translation, holding strong potential for improving non-invasive cancer phenotyping and/or assessment of early therapeutic response.

Bretta Russell-Schulz¹, Jasmyne Kassam², Michael Waine², Erin L MacMillan^1,3,4, Irene Vavasour¹, Helen Cross², Anthony Traboulsee², Robert Carruthers², and Shannon Kolind^2,5,6
1Radiology, UBC MRI Research Centre, Vancouver, BC, Canada, ²Medicine, University of British Columbia, Vancouver, BC, Canada, ³Philips Healthcare Canada, Markham, ON, Canada, ⁴Simon Fraser University's ImageTech Lab, Surrey, BC, Canada, ⁵Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁶Radiology, University of British Columbia, Vancouver, BC, Canada

This study establishes pre-treatment baseline metabolite concentrations for a longitudinal clinical trial for RRMS and PPMS using ¹H-MRS. The high MRS data quality and similar in FWHM across all participants creates a strong baseline for detecting change over time. Furthermore, knowing the pre-treatment concentration and tracking concentration changes in the MS subtypes compared to a baseline HC group will allow us to learn more about the mechanisms of action of this therapy.

Gerd Melkus^1,2, Michael Taccone^3,4, Ioana D Moldovan^4,5, John Woulfe^3,5,6, Gerard Jansen^3,7, Ian Cameron^1,2, Fahad AlKherayf^3,4,5, and Thanh Binh Nguyen^1,2
1Medical Imaging, The Ottawa Hospital, Ottawa, ON, Canada, ²Radiology, University of Ottawa, Ottawa, ON, Canada, ³University of Ottawa, Ottawa, ON, Canada, ⁴Division of Neurosurgery, The Ottawa Hospital, Ottawa, ON, Canada, ⁵The Ottawa Hospital Research Institute, Ottawa, ON, Canada, ⁶Division of Neurology, University of Ottawa, Ottawa, ON, Canada, ⁷Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, Canada

The main objective of this study is to evaluate the agreement of metabolites  between the MEGA-PRESS sequence (analyzing the edit-off spectrum) and a standard long TE PRESS sequence that is used in clinical routine for tumour characterization. The T2 corrected metabolite levels of NAA, Cho and Cr obtained from the edit-off spectrum of the MEGA-PRESS sequence are in good agreement with those obtained from the standard long TE PRESS sequence. No significant difference in the diagnostic accuracy was found.

Do-Wan Lee¹, Yeon Ji Chae², Monica Young Choi², Jae-Im Kwon³, Joongkee Min³, Chul‐Woong Woo³, Hwon Heo², Dong‐Cheol Woo^2,3, Jeong Kon Kim¹, Kyung Won Kim¹, Hyo Jeong Chin⁴, and Dong‐Hoon Lee^4
1Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ²Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ³Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of, ⁴Department of Radiological Science, College of Health Sciences, Yonsei University, Wonju, Korea, Republic of

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo proton magnetic resonance spectroscopy (¹H-MRS) at 7-T. The principal findings of the present study were significantly altered concentrations of gamma-aminobutyric acid, glutamate, myo-Inositol, tCr (creatine + phosphocreatine), and Glx (glutamate  + glutamine) in the hippocampus of the demyelination-induced rats relative to those in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Tianyao Wang¹, Danni Wang², Yujie Hu², Rong Guo^3,4, Yudu Li^3,4, Yibo Zhao^3,4, Jun Liu⁵, Zhi-Pei Liang^3,4, and Yao Li^2
1Radiology Department, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China, ²School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ³Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁵Radiology Department, Tong Ren Hospital Shanghai Jiao Tong University School Medicine, Shanghai, China

White matter tracts are known to be highly vulnerable to traumatic axonal injury. Myelin degradation is a major contributing factor for the white matter pathology in traumatic brain injury (TBI), but its relation to neurometabolite alterations is unclear. In this study, we used the latest SPICE technology to perform simultaneous 3D high-resolution MRSI and myelin water imaging to assess the relationship between myelin degradation and neurometabolic changes in acute mild TBI (mTBI) patients. Our results showed coupled MWF and NAA reductions in occipital CC tract of the patients, which provides new insights into TAI pathology in acute mTBI. 

Shiyu Tang^1,2, Su Xu^1,2, Donna Wilder³, Joseph Long³, Venkata Siva Sai Sujith Sajja^3,4, and Rao Gullapalli^1,2
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ²Center for Advanced Imaging Research (CAIR), University of Maryland School of Medicine, Baltimore, MD, United States, ³Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States, ⁴The Geneva Foundation, Tacoma, WA, United States

We studied the longitudinal changes in brain metabolism and impulsivity behavior in ferrets, a gyrencephalic animal model subjected to novel blast exposure conditions that closely mimic those encountered by Warfighters. Compared to rodents, the ferret model has greater similarities to human in terms of developmental process, brain structure and sophisticated behavior. Ferrets demonstrated increased behavioral impulsivity and higher glutamate and taurine in prefrontal cortex following blast exposure. Our findings are in agreement with clinical observations in patients, suggesting that this model is a good gyrencephalic animal model to study brain biochemical profile changes and neuropsychiatric alterations associated with blast exposure.

Sam H. Jiang¹, David M. Benedek², Patricia Spangler², James West², Catherine L. Dempsey², Ashley Phares², Brian Andrews-Shigaki³, Eduardo Coello¹, and Alexander P. Lin^1
1Center for Clinical Spectroscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States, ²Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ³Office of Naval Research, United States Navy and Marine Corps, Alexandria, VA, United States

Active duty service members and veterans with post-traumatic stress disorder (PTSD) refractory to evidence-based therapy were randomized to receive either riluzole, a glutamate modulator, or placebo adjunctive to selective serotonin reuptake inhibitor therapy over an 8-week period. Subjects underwent ¹H brain magnetic resonance spectroscopy scans pre- and post-treatment and were assessed longitudinally for PTSD symptomology using the Clinician-Administered PTSD Scale (CAPS). Subjects were stratified into improved and non-improved groups based on a decrease in CAPS score. Analyses on within- and between-group metabolite differences revealed that riluzole modulated the glutamate-glutamine cycle, improved neural energetics, and may have induced choline-linked neuroprotective inflammation.

Chun-Xia Li¹, Frank Tong², Doty Kempf¹, Leonard Howell¹, and Xiaodong Zhang^1
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Radiology, Emory University, Atlanta, GA, United States

Previous studies have suggested cerebral Choline (Cho) is a sensitive marker of acute stroke and could protect the tissue from ischemic injury. Also the relative connectivity (RelCon) could be a robust index to reveal the functional connectivity changes using resting state fMRI (rs-fMRI). The results indicated progressively increased RelCon in secondary somatosensory cortex (RelCon-S2) and a significant positive correlation between RelCon-S2 and relative cerebral Choline level (RelCho) from hyper-acute phase to 96 hours post stroke. The RelCon and RelCho combined detection might be an optimized and promising approach in management and prediction of stroke recovery.

Eduardo Coello¹, Victoria Sanchez¹, Marcia Louis¹, Huijun Liao¹, Sam Jiang¹, Wufan Zhao¹, Katherine M. Breedlove¹, Raymond Huang¹, and Alexander Lin^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States

This work introduces a reference frame for the evaluation of single-voxel spectroscopy scans of brain tumors. The goal of this work is to stratify the classification of spectra based on metabolic features to maximize their specificity. The method was developed using decision trees and tested with different sample classifications that included tumor vs. non-tumor voxels and IDH vs. non-IDH tumors.

Gasper Zupan^1,2, Sebastian Stefanovic³, Marjana Turk Jerovsek³, Borut Stabuc³, Georg Oeltzschner^4,5, Stefan Ropele⁶, Dusan Suput¹, and Andrej Vovk^1
1Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, ²Institute of Radiology, University Medical Center Ljubljana, Ljubljana, Slovenia, ³Department of Gastroenterology and Hepatology, University Medical Center Ljubljana, Ljubljana, Slovenia, ⁴Russell H. Morgan Department of Radiology and Radiological Sciences, The John Hopkins University School of Medicine, Baltimore, MD, United States, ⁵M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁶Department of Neurology, Neuroimaging Research Unit, Medical University of Graz, Graz, Austria

Liver cirrhosis (LC) is a worldwide public health problem. One of the complications of LC is hepatic encephalopathy which can present only as subtle cognitive impairment. Using advanced MR methods (MEGA-PRESS Spectroscopy and Quantitative Susceptibility Mapping), decreased striatal GABA levels, decreased susceptibility in caudate nucleus and increased susceptibility in putamen were demonstrated in LC patients compared to healthy controls. GABA levels and susceptibility in putamen correlated with the results of neuropsychological tests in the LC group compared to healthy controls. 

Yulu Song¹, Tao Gong¹, Muhammad G. Saleh^2,3, Mark Mikkelsen^2,3, Guangbin Wang ¹, and Richard Edden^2,3
1Shandong Medical Imaging Research Institute, Shandong University, jinan, China, ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, baltimore, MD, United States, ³FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, baltimore, MD, United States

The aim of this study is to test the hypothesis that levels of gamma-aminobutyric acid (GABA) in the upper brainstem are reduced in patients with PD compared to healthy controls, using edited magnetic resonance spectroscopy (MRS of GABA+). GABA+-edited MRS was performed in 7.5-ml voxels in the upper brainstem in 18 PD patients and 18 age- and sex-matched healthy controls (HCs), and the spectra were processed using the Gannet software. The lower GABA+ levels in the upper brainstem of the PD patients suggest that a GABAergic deficit in the brainstem may contribute to the dopaminergic pathology in PD.

David Jing Ma¹, Sabrina Gjerswold-Selleck², Yanping Sun³, Matt Mattingly Mattingly⁴, and Jia Guo^5
1Biomedical Engineering, Columbia University, New York, NY, United States, ²Columbia University, New York, NY, United States, ³Herbert Irving Comprehensive Cancer Centre, Columbia University, New York, NY, United States, ⁴Bruker BioSpin, Billerica, MA, United States, ⁵Department of Psychiatry, Columbia University, New York, NY, United States

Glutathione (GSH) is an important intracellular antioxidant in the brain. Various clinical human studies report its measurement by localized ¹H spectroscopy using MEGA-PRESS and achieve high reliability and accuracy of GSH measurements at 3 T. As of today, animal model studies conducted at higher fields significantly enhance the armamentarium of tools available for the probing brain function and brain pathologies. However, even though mice are widely used in research, limited studies of GSH in mouse models are conducted. In this study, we demonstrate that MEGA-PRESS is a feasible technique to measure GSH in the mouse brain in vivo at 9.4T. 

Subechhya Pradhan^1,2,3, Sudeepta Basu⁴, Kushal Kapse¹, Devon Fisher¹, Stephanie Norman¹, and Catherine Limperopoulos^1,2,3
1Developing Brain Institute, Children's National Hospital, Washington, DC, United States, ²Radiology, Pediatrics, George Washinton University, Washington, DC, United States, ³Radiology and Diagnostic Imaging, Children's National Hospital, Washington, DC, United States, ⁴Neonatalogy, Children's National Hospital, Washington, DC, United States

Preterm brain metabolism studies using magnetic resonance spectroscopy (MRS) demonstrate an association between abnormal biochemistry and brain injury. To our knowledge, there are no reports on the reproducibility of these measurements as well as the optimal pulse sequence to measure each metabolite in the preterm brain. In this study, results of same-session reproducibility of metabolite concentration measurements from 15 preterm scanning sessions using 4 different pulse sequences are presented.

Iris Asllani^1,2, Francesco Di Lorenzo¹, Balazs Orzsik¹, Guillaume Madelin³, Neil Harrison⁴, and Mara Cercignani^1
1University of Sussex, Brighton, United Kingdom, ²Rochester Institute of Technology, Rochester, NY, United States, ³New York University, New York, NY, United States, ⁴University of Cardiff, Cardiff, United Kingdom

²³Na MRI data were acquired on healthy volunteers ~15 mins after either anodal, cathodal, or sham application of tDCS in the motor cortex. Tissue specific [Na] concentration images were obtained using a partial volume correction algorithm previously developed for ASL MRI. There was an average 14% increase in gray matter sodium concentration, [Na]_GM, across the group following the anodal tDCS; no significant change was observed for the sham application. Of note, all subjects exhibited a widespread pattern of increased [Na]_GM similar to that reported in ASL MRI studies that have measured changes in CBF also following anodal tDCS of M1.

Charles S. Springer¹, Brendan Moloney¹, Eric Baker¹, Martin M. Pike¹, and Xin Li^1
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States

The first aMRI [activity MRI] maps of the awake, heathy human brain are presented.  They show differences in cell density [ρ (cells/μL)], average cell volume [V (pL)], and on-going metabolic activity among different brain tissues.  Metabolic activity is represented by the mean steady-state cellular water efflux rate constant [k_io], which reflects homeostatic cytolemmal Na⁺,K⁺-ATPase [NKA] enzymatic turnover.  Cortical gray matter [GM] ρ is less than white matter [WM] ρ, while V_GM > V_WM.  Most interesting is the quite large WM k_io, 30 s^-1.  WM NKA activity per cell is considerably larger than in cortical GM.