This application is a competitive renewal of an R01 completing its first cycle. The overall goal is to use in vivo magnetic resonance diffusion imaging (dMRI) to study white matter (WM) pathology in schizophrenia (SZ). Measurement of microstructural WM pathology has the potential to have a huge impact on new SZ treatment strategies (anti-inflammatory drugs, drugs promoting cell regeneration, myelin protective medication, etc.) The previous project cycle was focused on diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) models, and established that there are subtle abnormalities in the WM in SZ. In this new proposal we plan to develop more sensitive probes of tissue microstructure using advanced dMRI scanning and analysis techniques, to help explore the nature of the subtle abnormalities and pinpoint specific micro- pathology. The proposed advances in dMRI include development of methods for multiple-shell imaging to en- able measurement of the full 3D diffusion function (the propagator), and implementation of the recently developed double pulsed field gradient (double-PFG) sequence on a clinical scanner. These technologies will in- crease the scan time but will provide more specific information about tissue microstructure, increasing the sensitivity to brain changes and abnormalities. To make both double-PFG and multiple-shell measurements feasi- ble in clinical time, we propose to employ compressed sensing, an advanced sampling and reconstruction strategy that allows reconstruction of the image data with considerably fewer data points than are traditionally required. We will develop novel quantitative analysis methods, with special focus on analysis of the unique data produced by the double-PFG sequence. This type of data has not yet been investigated in clinical studies. Finally we will scan patients with schizophrenia and normal controls with the proposed protocols and apply the analysis methods to study group differences. We expect that upon successful completion of this project, we will have developed a clinically feasible dMRI paradigm including scanning and analysis pipelines that will help identify and quantify subtle changes in diffusion induced by pathology, which cannot be detected with current technology.

Public Health Relevance

The overall goal is to use in vivo magnetic resonance diffusion imaging (dMRI) to study white matter (WM) pathology in schizophrenia (SZ). The proposed advances in dMRI include development of methods for multiple- shell imaging to enable measurement of the full diffusion function, and implementation of the recently developed double pulsed field gradient (double-PFG) sequence on a clinical scanner. We will scan patients with schizophrenia and normal controls with the proposed protocols and apply the analysis methods to detect cellular alterations in the WM in SZ.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH074794-07
Application #
8452073
Study Section
Special Emphasis Panel (ZRG1-NT-L (09))
Program Officer
Rumsey, Judith M
Project Start
2005-07-01
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
7
Fiscal Year
2013
Total Cost
$657,629
Indirect Cost
$284,555
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Albi, Angela; Meola, Antonio; Zhang, Fan et al. (2018) Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects. J Neuroimaging 28:173-182
Özarslan, Evren; Yolcu, Cem; Herberthson, Magnus et al. (2018) Influence of the size and curvedness of neural projections on the orientationally averaged diffusion MR signal. Front Phys 6:
Zhang, Fan; Savadjiev, Peter; Cai, Weidong et al. (2018) Whole brain white matter connectivity analysis using machine learning: An application to autism. Neuroimage 172:826-837
Ning, Lipeng; Rathi, Yogesh (2018) A Dynamic Regression Approach for Frequency-Domain Partial Coherence and Causality Analysis of Functional Brain Networks. IEEE Trans Med Imaging 37:1957-1969
McCarthy-Jones, Simon; Oestreich, Lena K L; Lyall, Amanda E et al. (2018) Childhood adversity associated with white matter alteration in the corpus callosum, corona radiata, and uncinate fasciculus of psychiatrically healthy adults. Brain Imaging Behav 12:449-458
Lyall, A E; Pasternak, O; Robinson, D G et al. (2018) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry 23:701-707
Seitz, Johanna; Rathi, Yogesh; Lyall, Amanda et al. (2018) Alteration of gray matter microstructure in schizophrenia. Brain Imaging Behav 12:54-63
Zhang, Fan; Wu, Weining; Ning, Lipeng et al. (2018) Suprathreshold fiber cluster statistics: Leveraging white matter geometry to enhance tractography statistical analysis. Neuroimage 171:341-354
Saito, Yukiko; Kubicki, Marek; Koerte, Inga et al. (2018) Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia. Brain Imaging Behav 12:229-237
Nilsson, Markus; Larsson, Johan; Lundberg, Dan et al. (2018) Liquid crystal phantom for validation of microscopic diffusion anisotropy measurements on clinical MRI systems. Magn Reson Med 79:1817-1828

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