NAMIC Core 3.1 Overview: Harvard/BWH and Dartmouth

1. NAMIC Core 3.1 Overview: Harvard/BWH and Dartmouth Structural and Functional Connectivity in Schizophrenia October 17, 2006

2. Overview Analysis of white matter fiber tracts and the nodes connected by these pathways: • Uncinate fasciculus • Cingulate fasciculus • Arcuate fasciculus • Corpus callosum • Anterior limb of internal capsule • Temporal pole, amygdala-hippocampal complex, STG and inferior parietal lobule, thalamus Focus on DT-MRI and fMRI, but also MTR and structural MRI. October 17, 2006

3. Data Acquisition Recruitment of 60 chronic, 60 first episode, and 120 normal control patients. 1.5T. So far, we recruited and shared with Core1: 40 chronic schizophrenics and 40 controls scanned with the old DTI LSDI protocol (1.7 x1.7 x5 mm, 6 directions, 1 baseline) New sequence: 3T.(To be uploaded on BIRN followed by additional data. Contact information regarding data: marc@bwh.harvard.edu; shenton@bwh.harvard.edu) So far, we recruited and scanned 14 schizophrenics and 12 controls with SENSE EPI protocol (1.7 x1.7 x1.7 mm, 51 directions, 8 baselines). All these subjects have also 1 x 1 x 1mm structural scans available. We can make the 26 available or the 12 controls. Subjects will not be identified by diagnosis (Note: on going collection). October 17, 2006

4. Data Acquisition Dartmouth (ongoing collection) DTI – GE 1.5T Using our initial 1.5T DTI protocol we have scanned 43 potentially usable subjects: Pre-processed and reviewed - 17 patients and 11 controls Awaiting pre-processing and review - 15 other subjects All have 0.9375x0.9375x1.5mm SPGR structural scan (Samples to be uploaded on BIRN ASAP; followed by additional data Contact for DTI and SPGR: John.D.West@dartmouth.edu or A Saykin) Philips 3T data beginning to be acquired – sample subject with DTI, fMRI motor task, and MPRAGE structural was incorporated in NAMIC tutorial

5. Data Acquisition Dartmouth (ongoing collection) fMRI – GE 1.5T Auditory-verbal n-back Working Memory Task - 20 patients and 20 Controls Verbal Episodic Encoding/Recognition Task (event-related) - 14 patients and 9 Controls (samples on BIRN site; contact: saykin@dartmouth.edu)

6. Available Labelmaps • Amygdala/hippocampal complex • Middle temporal gyrus and inferior temporal gyrus • Superior temporal gyrus • Temporal pole and insular cortex • Male caudate nucleus • Female caudate nucleus (uploaded to mBIRN; contact for more information: marc@bwh.harvard.edu; shenton@bwh.harvard.edu) October 17, 2006

7. Methodologies fMRI: DT-MRI: • Fiber organization (diffusivity). • Cross sectional areas of fiber bundles. • Asymmetries (left vs. right, hemispheric). • Fiber tractography based connectivity and asymmetry estimation. • Measures of diffusivity (FA, RA, trace, ...). • Pattern of BOLD signal change in the networks of interest. • Changes in spatiotemporal patterns. Structural MRI: • Volume. • Area. • Shape. MTR: • Myelinization. Correlation of clinical status measures with image analysis results. October 17, 2006

8. General Hypotheses • Decreased fiber organization. • Decreased cross-sectional areas (ROI areas). • Decrease left>right asymmetry (also myelin decrease?). • Volume decreases lateralized to the left. • Correlations with clinical measures. • fMRI: connection between activation and connectivity measures. October 16, 2006

9. Work relating to fasciculi UF: 2 ROI tractography analysis with mean FA measures, doDTI submitted to Brain. CF: previously defined ROIs, tractography with behavioral Stroop data, doDTI submitted to Archives of General Psychiatry. AF: Registration of Susumu Mori’s atlas to our cases. Slicer  Nonlinear FA to FA. No results. Need better registration. CC: (1) Tractography. Fibers seeded in one slice CC ROI. Automated fiber clustering results in ROI color coded based on fiber clustering (Slicer,MIT Collaboration). (2) Atlas based approach warping a CC subdivision to individual cases (UNC Collaboration). ALIC: Work in progress. Tractography from anterior and posterior limb of the internal capsule. Slicer October 17, 2006

10. Work relating to fasciculi connections STG: Mean FA, mean diffusivity within ROI defined on SPGR Slicer, submitted to Biological Psychiatry. October 17, 2006

11. Collaborations within NAMIC UNC: Shape analysis of caudate, CC subdivision. MIT: Optimal path analysis (using fMRI activation for seeding), Stochastic tracking, Spectral clustering, Segmentation (STG, amygdala/hippocampal complex). GaTech: Semiautomatic parcellation of the striatum, Spherical wavelets. Utah: Smoothing of diffusion weighted images. October 17, 2006

12. Old Wish-List Revisited • Anatomical Atlas (gray and white matter combined, including fiber tracts) Susumu Mori’s atlas for white matter. • Combination of different modalities (functional and anatomical connectivity)  still needed. • Improved fiber tracking (smoothing, regularization, anatomical regions for automatic seeding) ongoing. • Statistical analysis for shape analysis software: compromise between too conservative and uncorrected statistics  FDR approach by Martin Styner. • Temporal lobe automated segmentation  still needed,STG tested, MTG/ITG under development. • Basal ganglia segmentation  still needed,semi-automated parcellation, segmentation still manual. October 17, 2006

13. Projects/Papers Submitted or About To Be Submitted • UF: 2 R01 tractography analysis with mean FA measures, doDTI, submitted to Brain. • CF: Previously defined ROIs, tractography with behavior Stroop data, doDTI, submitted to Archives General Psychiatry. • STG: STG automatic segmentation (MIT) – submitted toNeuroImage. • STG: Mean FA, mean diffusivity within ROI defined on SPGR, Slicer, ready to be submitted – Biological Psychiatry. • Ca: Caudate shape analysis (UNC) – ready to be submitted to Biological Psychiatry. October 17, 2006

14. Core 3.1- Short Term Goal for Paper Submission Prior to 08/2007 • CC(1):Tractography. Fibers seeded in one slice CC ROI. Automated fiber clustering results in ROI color coded based on fiber clustering (Slicer, MIT Collaboration). • CC(2): Atlas based approach warping a CC subdivision to individual cases (UNC Collaboration). • ALIC: Tractography from anterior and posterior limb of internal capsule (Slicer, MIT Collaboration). • AF and other fibers: Registration of new 3T diffusion data using new techniques as discussed at meeting. (UNC and GE(?)). (Previously used Susumu Mori’s atlas with FA to FA registration, with no results on 1.5 T diffusion data). • Ca: Shape analysis of the caudate with spherical wavelets (GaTech). • Striatum: Semiautomated parcellation of the striatum (GaTech). • UF and other fibers: Registration of 1.5T DTI using new techniques discussed at meeting. Use template to extract data from relevant fiber tracts. (UNC, Dartmouth/IU & Utah?). Will be uploading sample sets for UNC to test in the next few days. Other data to follow. October 17, 2006

15. Core 3.1 – Long Term Goals • Co-registration of structural, diffusion, and functional data – multimodal imaging data. (Nothing in Slicer, we use SPM). • DWI registration; fiber registration. • Improved fiber tracking (smoothing, regularization, anatomic regions for automatic seeding). • Fiber asymmetry computation. • Statistical analysis for shape analysis software (FDR approach by Martin Styner - ongoing). • Tractography of white matter structures seeded in gray matter areas (e.g., stochastic tracking- ongoing). • 3T artifact removal. • Segmentation of temporal lobe and basal ganglia. • Anatomical Atlas (gray and white matter combined, including fiber tracts – Note this is both aSHORT TERM & LONG TERM Goal). October 17, 2006

16. Conclusion A lot of structural work has been accomplished. Need for better diffusion tools. Critical Need for Effective ways to combine multimodal data. October 17, 2006