MRS of Disease, Injury & Pathology in CNS
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Wednesday 9 May 2012
Room 212-213  16:00 - 18:00 Moderators: Jeffry R. Alger, William M. Spees

16:00 0488.   Comparison of Cerebral Glutamate and GABA in Schizotypal Personality Disorder using Spectral Editing and 2D Correlated Spectroscopy
Alexander Peter Lin1, Huijun Liao1, Ana Cadena1, Saadallah Ramadan2, Israel Molina3, and Robert McCarley4
1Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, 2School of Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia, 3Laboratory of Neuroscience, Veterans Affairs Boston Healthcare System, Brockton, MA, United States,4Psychiatry at Veterans Affairs Boston Healthcare System, Harvard Medical School, Brockton, MA, United States

Schizotypal personality disorder shares biological, genetic, and clinical features of schizophrenia however little is known the alterations of brain neurochemistry, in particular the important neurotransmitters of GABA and glutamate. Our goal was to use spectral editing and 2D correlated spectroscopy techniques to measure the concentration of these chemicals in SPD subjects. Our results show a decrease in GABA and increase in glutamate in SPD subjects when compared with controls. Results of the different MRS methods were also compared and showed to share the same results however 2D COSY provided additional information beyond the other techniques.

16:12 0489.   Lateralized Cortical and Subcortical Biochemical Abnormalities in Late-life Major Depression: A Proton MR Spectroscopy Study at 3T
Shaolin Yang1,2, Olusola Ajilore1, Minjie Wu1, Melissa Lamar1, and Anand Kumar1
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, 2Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

Neuroanatomical abnormalities have been identified in patients with late-life mood disorders. This study examined the biochemical correlates of late-life major depression in the cortical and subcortical gray matter and white matter by using proton MR spectroscopy at 3T. Relative to comparison subjects, the patients with late-life major depression had significantly elevated concentrations of myo-inositol in right frontal white matter and left head of caudate. No other neurochemical differences were observed between groups. The concentrations of myo-inositol in both regions were significantly correlated with the depressive symptomatology and the positive correlation between the concentration of myo-inositol and cognitive function as seen in the control group attenuated in the patient group.

16:24 0490.   Reduced Hippocampal NAA/Choline in Blast Related Traumatic Brain Injury with Memory Impairment: A 7T MRSI Study
Hoby Hetherington1, Hamada Hamid2, Rebecca Czlapinski2, Jullie Pan1, Faris Bandak3, Geoffrey Ling3, and Nihal deLanerolle1
1Neurosurgery, Yale University, New Haven, CT, United States, 2Neurology, West Haven VA, West Haven, CT, United States, 3Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Mild traumatic brain injury due to explosive blast exposure has gained attention for its prevalence in recent conflicts and a lack of positive imaging correlates in conventional MRIs. Despite the absence of conventional MRI findings, these patients express a constellation of ongoing deficits including memory dysfunction, migraines, and a variety of behavioral changes. Using high resolution MRSI at 7T we have measured a significant decline in NAA/Ch (p<0.05) from the anterior hippocampi in patients exposed to blast with self-reported memory dysfunction. These findings are consistent with the anatomical localization of memory function (hippocampus and temporal lobe).

16:36 0491.   Multimodal Validation of Oxidative Stress as a Pathophysiological Model of Chronic Fatigue Syndrome
Dikoma C Shungu1, Nora Weiduscat1, James W Murrough2, Xiangling Mao1, Sarah Pillemer2, Marvin S Meddow3, Jonathan P Dyke1, Benjamin H Natelson4, Julian M Stewart3, and Sanjay J Mathew5
1Radiology, Weill Cornell Medical College, New York, New York, United States, 2Psychiatry, Mount Sinai School of Medicine, 3New York Medical College,4Beth Israel Medical Center, 5Baylor College of Medicine

This study used multiple MR methods, including MRS measurement of the major antioxidant glutathione (GSH), to test the hypothesis that oxidative stress plays a major role in the pathophysiology of chronic fatigue syndrome (CFS).

16:48 0492.   A Sodium Imaging Study of Huntington's Disease at 4T
Sandro Romanzetti1, Kathrin Reetz1,2, Imis Dogan2,3, Christian Saß4, Cornelius Werner2, Johannes Schiefer2, Daniel Fiege1, Jörg B. Schulz2,3, and N.Jon Shah1,5
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Jülich, Jülich, Germany, 2Department of Neurology, RWTH Aachen University, Aachen, Germany, 3Translational Brain Medicine, JARA, Aachen, Germany, 4Department of Neurology, University Hospital Münster, Münster, Germany, 5JARA - Faculty of Medicine, RWTH Aachen University, Aachen, Germany

The proven sensitivity of sodium MRI to cell viability and death has been applied for the first time in this study for the characterization of pre-symptomatic as well as symptomatic patients affected by Huntington’s Disease (HD). Tissue Sodium Concentration maps of a group of patient were compared to those from an age-matched control group. A significant enhancement in sodium concentration was detected in the bilateral striatum, a key region, in HD. It has been shown that this imaging modality may provide a deeper insight into the pathophysiological mechanisms of tissue injury in HD.

17:00 0493.   Abnormal Response to Visual Cortex Activation in Early Stage Huntington Disease Patients using 31P-NMR Spectroscopy
Fanny Mochel1, Tra-My N'Guyen1, Dinesh K Deelchand2, Daisy Rinaldi1, Romain Valabregue3, Claire Wary4, Pierre G Carlier4, Alexandra Durr1, and Pierre-Gilles Henry2
1UMR S975, Institut du Cerveau et de la Moelle, Hopital La Salpetriere, Paris, France, 2Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 3CENIR, Institut du Cerveau et de la Moelle, Hopital La Salpetriere, Paris, France, 4NMR Laboratory AIM-CEA, Institute of Myology, Pitié-Salpêtrière University Hospital, Paris, France

We measured dynamic 31P NMR spectra in human visual cortex before, during, and after visual activation in controls and in patients with Huntington’s Disease. In controls, we observed an 11% increase in Pi/PCr ratio (p=0.012) and a 13% increase in Pi/ATP ratio (p=0.008) during brain activation. In contrast, in HD patients, both Pi/PCr and Pi/ATP ratios were unchanged during and after visual stimulation, most likely reflecting reduced mitochondrial activity. This may provide a new functional biomarker of brain energy deficit to assess therapeutic efficacy in HD in clinical trials.

17:12 0494.   Longitudinal changes in neurochemical profiles of Huntington’s disease mouse models
Ivan Tkac1, Lori Zacharoff2, and Janet M Dubinsky2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Department of Neuroscience, University of Minnesota, Minneapols, MN, United States

In vivo 1H NMR spectroscopy at 9.T was used to investigate neurochemical changes in three different mouse models of Huntington’s disease; transgenic R6/2, knock-in Q140 and bacterial artificial chromosome transgenic BACHD mouse models. Substantial differences in metabolite age-dependent trajectories were observed between these mouse models of HD. Metabolite changes mostly localized in striatum of the Q140 mice more closely resembles phenotypes of the human HD. Therefore, the Q140 mouse model might be preferential for studies of HD and its treatment.

17:24 0495.   MR detectable metabolic changes associated with mutant IDH
Sarah Woods1, Myriam Marianne Chaumeil1, Alessia Lodi1, Robert M Danforth1, Aaron Robinson2, Joanna J Philips2, and Sabrina M Ronen1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States

Our goal was to assess the MRS-detectable metabolic changes associated with mutation of the isocitrate dehydrogenase (IDH) gene in two isogenic glioblastoma cell lines: U87IDHmutant and U87IDHwild-type. 1H MRS of extracts confirmed the presence of 2HG and detected several metabolic changes including elevated phosphocholine and elevated lactate in U87IDHmutant compared to U87IDHwt. The pyruvate-to-lactate conversion as measured by hyperpolarized 13C MRS was significantly lower in U87IDHmutant cells likely due to a drop in lactate dehydrogenase activity. Our studies inform on the metabolic consequence of the IDH mutation and identify biomarkers of the mutation.

17:36 0496.   Correlation of 31P MRS Metabolite Ratios and Near-Infrared Spectroscopy Measurements of the Redox State of Cytochrome Oxidase During and After Hypoxia-Ischemia in the Piglet
Alan Bainbridge1, Ilias Tachtsidis2, Stuart Faulkner3, Sonya Mahony2, David Price1, David L Thomas4, Ernest B Cady1, Nicola J Robertson3, and Xavier Golay4
1Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London, United Kingdom, 2Medical Physics and Bioengineering, University College London, United Kingdom, 3Institute for Women's Health, UCL, United Kingdom, 4Institute of Neurology, UCL, United Kingdom

To investigate brain haemodynamic and metabolic changes during transient hypoxia-ischemia (HI) and recovery we integrated broadband near-infrared spectroscopy (NIRS – to characterise the time courses the redox state of cytochrome-c-oxidase) with 31P MRS. We speculate that during recovery from HI, different populations of cells recover at different rates and that the relationships observed occur as a result of this. These recovery curves could be used to estimate the extent of permanent mitochondrial damage that occurs during HI in this model and thus the proportion of tissue amenable to salvage via therapeutic intervention post HI.

17:48 0497.   
In vivo comparison of total and hyperpolarized lactate levels assessed by localized 1H MRS and hyperpolarized 13C MRSI in glioblastoma models at 14.1Tesla
Myriam Marianne Chaumeil1, Gerd Melkus1, Sarah Woods1, Robert M Danforth1, Alessia Lodi1, Aaron Robinson2, Joanna J Philips2,3, and Sabrina M Ronen1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States, 3Pathology, University of California, San Francisco, San Francisco, CA, United States

Localized 1H MRS and hyperpolarized (HP) 13C MRSI were performed in vivo at 14.1Tesla to assess total and HP lactate levels, respectively, in two orthotopic models of glioblastomas with significantly different intracellular lactate levels: U87IDHmut[Lac]>U87IDHwt[Lac]. In line with the intracellular levels, in vivo 1H lactate levels were significantly higher in U87IDHmut. In contrast, HP lactate-to-noise and lactate-to-pyruvate ratios from the same tumor voxel were not significantly different between the cell lines. This discrepancy confirms that HP 13C MRSI and 1H MRS provide complementary information, the 1H-detected lactate level not being a dominant factor in the detected HP lactate production.