In Vivo 3D Lithium MRI of the Human Brain
Fernando Emilio Boada¹, Yongxian Qian¹, Ariel Gildengers², Mary Phillips², David Kupfer^2
1MR Research Center, University of Pittsburgh, Pittsburgh, PA, United States; ²Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States

Bipolar Disorder (BPD) is a devastating mental illness that is often treated using Lithium Carbonate therapy. Unfortunately, lithium carbonate therapy has life-threatening side effects. Moreover, its mechanisms of action and preferred accumulation sites in the in vivo brain continue to be unknown sixty years after its original introduction. A methodology for studying the spatial distribution of lithium carbonate in the brain of BPD subjects could, therefore, be an invaluable tool for studying this disease. In this work we present the first demonstration of 3D lithium MRI in the in Vivo human Brain at 7 Tesla.

4T ⁷Li MRSI in the Brains of Bipolar Disorder Subjects
Jing-Huei Lee^1,2, Matthew M. Norris¹, Caleb M. Adler^2,3, Elizabeth E. Macaluso², Wen-Jang Chu^2,3, Richard A. Komoroski^2,3, Stephen M. Strakowski^2,3
1Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States; ²Center for Imaging Research, University of Cincinnati, Cincinnati, OH, United States; ³Psychiatry, University of Cincinnati, Cincinnati, OH, United States

This work proposes and compares two approaches for ⁷Li MRSI data analysis: Method I: 1D-3D vs. Method II: 3D-1D approach. The result shows that there is virtually no difference between these two approaches. However, Method I is preferred for use in future data analysis since it is simple in practice. Furthermore, this study is the first demonstration of the ⁷Li distribution in the brain of bipolar patients who are on lithium therapy. The distribution is not uniform throughout the entire brain for all patients, which is unexpected. Further investigations are ongoing.

Decreased PHi and [ADP] in Anterior Cingulate Cortex of Bipolar Disorder: Further Evidence of Mitochondrial Dysfunction
Jonathan Dudley¹, Wen-Jang Chu^2,3, Xin Wang¹, Matt Norris¹, Jing-Huei Lee^1,3
1Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States; ²Psychiatry, University of Cincinnati, Cincinnati, OH, United States; ³Center for Imaging Research, University of Cincinnati, Cincinnati, OH, United States

The theory of mitochondrial dysfunction in bipolar disorder (BD) has been supported by numerous MRS studies.  However, the absolute quantitation of phosphor metabolites in this disease has not been well studied.  This work is to determine phosphor metabolite concentrations in the anterior cingulate cortex among different subject groups.  The results were in concordance with the theory of mitochondrial dysfunction, showing a decrease in intracellular pH and [ADP] in manic and mixed BD patients relative to controls.

Metabolic Changes in Medication-Free Patients with Bipolar and Unipolar Disorder
Ulrike Dydak^1,2, Jonathan M. Nixon¹, Mario Dzemidzic³, Harish Sai Karne⁴, Amit Anand^4
1School of Health Sciences, Purdue University, West Lafayette, IN, United States; ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States; ³Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States; ⁴Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States

Changes in brain metabolism were studied in medication-free patients with bipolar and unipolar disorder and compared to matched healthy controls. 2D MRSI data acquired in an axial slice including thalamus, anterior and posterior cingulate cortex (ACC & PCC) were analyzed using LCModel. Significant decreases in NAA/ creatine were found in bipolar patients compared to healthy controls in the right thalamus and right ACC. Furthermore, when comparing bipolar to unipolar patients, significant decreases in the choline/creatine ratio were observed in the right thalamus. No significant group differences were found in the PCC nor any of the left hemisphere regions of interest.

Dissociation of Anterior Cingulate Glutamate and Induced Theta EEG Activity in Schizophrenia
Antonio Napolitano¹, Kathrin Doege², Mallikarjun Pavan², Peter Liddle², Dorothee P. Auer^1
1Academic Radiology, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ²Division of Psychiatry, University of Nottingham, United Kingdom

The glutamate hypothesis stimulated over the last two decades several MRS studies to research alterations of glutamate levels in schizophrenia. In this study, we used a combined EEG/MRS protocol to investigate whether prefrontal glutamate levels are altered in patients with early schizophrenia and whether there is an interrelation between glutamate and theta activity in schizophrenia.

Tissue Specific Changes in Brain Phosphodiesters in Late Life Major Depression
David G. Harper^1,2, J. Eric Jensen^2,3, Caitlin Ravichandran^2,4, E. Yusuf Sivrioglu⁵, Daniel Iosifescu^6,7, Perry Renshaw⁸, Brent Forester^2,9
1Geriatric Psychiatry, McLean Hospital, Belmont, MA, United States; ²Psychiatry, Harvard Medical School, Belmont, MA, United States; ³Neuroimaging Center, McLean Hospital, Belmont, MA, United States; ⁴Laboratory for Psychiatric Biostatistics, McLean Hospital, Belmont, MA, United States; ⁵Psychiatry, Uludag University, Bursa, Turkey; ⁶Psychiatry, Massachusetts General Hospital, Boston, MA, United States; ⁷Psychiatry, Harvard Medical School, Boston, MA, United States; ⁸Psychiatry, University of Utah, Salt Lake City, UT, United States; ⁹Geriatric Psychiatry, Mclean Hospital, Belmont, MA, United States

Biological membranes serve numerous, essential cellular functions.  MRI findings in late life depression include increased white matter hyperintensities and reduced fractional anisotropy as measured by diffusion tensor imaging suggesting that membrane integrity, especially in white matter, may be compromised. Phosphatidylethanolamine, in the inner mitochondrial membrane, serves an essential function and is synthesized via a unique pathway not involving phosphoethanolamine.  We  hypothesized that glycerophosphocholine  (GPCho) and glycerophosphoethanolamine (GPEtn), particularly in white matter, will be increased in late-life depression, and we hypothesized that GPEtn will be altered fundamentally differently than GPCho due to the additional pathway of the inner mitochondrial membrane and that GPEtn would therefore show changes in gray matter.

¹H MRS Measurement of Brain Glutathione Supports Increased Oxidative Stress in Major Depressive Disorder
Sanjay J. Mathewew¹, Xiangling Mao², Sarah Pillemer¹, James W. Murrough¹, Dikoma C. Shungu^2
1Psychiatry, Mount Sinai School of Medicine, New York, NY, United States; ²Radiology, Weill Cornell Medical College, New York, NY, United States

A large body of anecdotal evidence now implicates increased oxidative stress in a number of pathophysiologic models of major depressive disorder (MDD). In this study, the first in vivo ¹H MRS measurements of the primary cellular antioxidant glutathione (GSH) were made in the occipital lobe of MDD patients and found to be significantly decreased compared to healthy control subjects, which supports the presence of increased oxidative stress in the disorder.

Evidence of Age Effects in Cortical Areas But Not in the Subcortex of ADHD Children: A Multi-Voxel In Vivo ³¹P Spectroscopy Study at 4 Tesla
Jeffrey A. Stanley¹, Dalal Khatib¹, Rachel M. Dick¹, Olivia A. McGarragle¹, Frank P. MacMaster¹, Vaibhav A. Diwadkar¹, Arthur L. Robin¹, David R. Rosenberg^1
1Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States

Attention Deficit Hyperactivity Disorder (ADHD) is a serious public health problem that affects between 3 to 9% of children and accounts for between 30 to 40% of child referrals to mental health services. While the cause of this illness remains poorly understood, ADHD is increasingly seen as a neurodevelopmental disorder. In vivo ³¹P spectroscopy is a neuroimaging method that is sensitive in detecting biochemical changes as the brain develops. The purpose of this study is to provide further evidence of a developmental mechanism where early maldeveloped corticostriatal pathways may impact the maturational integration of prefrontal corticostriatal pathways in pediatric ADHD.

Disruption of Commissural White Matter Tracts in Pediatric Bipolar Disorder
Hao Huang¹, Kirti Saxena², Annie Walley², Min Xu¹, Nancy Rollins^3
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States; ³Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Identifying early signs of bipolar disorder is important because it may enable health care providers to intervene earlier and prevent progression of increased morbidity and personal dysfunction. Commissural tracts including corpus callosum (CC) and anterior commissure (AC) are the research target in this study. In our study, we acquired high resolution DTI from 10 pediatric bipolar patients and 10 age matched control subjects. We found that AC and anterior segment of CC has statistically smaller FA. Compared to DTI results of adult BP, the disruption pattern caused by BP demonstrates anterior to posterior pattern from childhood to adult.

Atypical Development of White Matter Microstructure in Adolescents with Autism Spectrum Disorders
Kun-Hsien Chou¹, I-Yun Chen², Ya-Wei Cheng², Jean Decety³, Yang-Teng Fan², Ching-Po Lin^2,4
1Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; ²Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; ³Departments of Psychology and Psychiatry, The University of Chicago, Chicago, United States; ⁴Institute of Biomedical imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan

Autism spectrum disorders is a common brain developmental disorder that occurs in one in 150 children. It is characterized by early onset of impaired social reciprocity and communication difficulties, along with restricted interest and stereotyped behavior. Several brain morphometry studies suggested that cascade failure of neurodevelopment is the most likely the core deficit of ASD. But whether aberrant WM development persisted into later childhood and adolescence was a crucial issue to probe. The aim of the present study was to examine WM microstructure using diffusion tensor imaging (DTI) and to investigate its relations to age in adolescents with ASD.