Function BIRN Science

FBIRN Goals Develop multi-site functional neuroimaging tools. Develop the capability to analyze, as a single data set, data acquired from multiple sites using tools developed from multiple sites. Implications for clinical applications and FDA approvals in addition to research.

The FBIRN Aims Calibration: –Assess and correct for the major sources of multi-site variation Cognitive Tasks: –Develop robust protocols for multi-site fMRI studies Analysis: –Develop methods to analyze multi-site fMRI data Tools: –Develop a scalable IT application toolkit to support multi-site fMRI studies Dissemination: –Make the tools, procedures, and collected datasets widely available

Research Plan 2005: Series B/C You Are Here March 2008: 3 rd year Progress Report due!!

5 FBIRN IT - We’re Up and We’re Mediated! UNM HID UMN HID UI HID Duke HID UCSD HID UCI HID BWH HID MGH HID Yale HID UCLA HID Stanford HID p1 p2 = Mediator tested = PostgreSQL test site = ph 1 and/or ph 2 data in DB Last year

6 FBIRN IT - We’re Up and We’re Populated UNM HID UMN HID UI HID Duke HID UCSD HID UCI HID BWH HID MGH HID Yale HID UCLA HID Stanford HID p1 p2 = Mediator tested = PostgreSQL test site = ph 1 and/or ph 2 data in DB UNM HID UMN HID UI HID Duke HID UCSD HID UCI HID BWH HID MGH HID Yale HID UCLA HID Stanford HID p1 p2 = Data Integration Environment = PostgreSQL test site = Phase 1 / Phase 2 data p1 p2 Duke: 67 BWH: 22 MGH: 12 UCLA: 54 UCSD: 6 UCI: 71 UNM: 57 UI: 64 UMN: 57 Yale: 66 Duke: 67 BWH: 22 MGH: 12 UCLA: 54 UCSD: 6 UCI: 71 UNM: 57 UI: 64 UMN: 57 Yale: Subject Visits 3174 Subject Assessments This year

What have we learned from Phase II? QC of uploaded datasets –Differences between formal protocol and what was actually done Importance of interoperability of datasets with analysis tools Keeping track of what you have done- data provenance Keeping terms straight- database semantic markup

Neuroinformatics progress Last fall ’ s milestone: Wrap and query BrainMap (non HID and not BIRN); GCRC This fall: BrainMap wrapped and registered. Mediated queries underway!

Neuroinformatics progress Programmers Week, May in Iowa See also the posters later today HID Interface improvementsHID Interface improvements HID, CALM code walkthroughsHID, CALM code walkthroughs Protocols added to database schemeProtocols added to database scheme XCEDE 2.0XCEDE 2.0 Integration of Freesurfer derived ROIsIntegration of Freesurfer derived ROIs Webservices/portlets trainingWebservices/portlets training

The FBIRN Aims Calibration: –Assess and correct for the major sources of multi-site variation Cognitive Tasks: –Develop robust protocols for multi-site fMRI studies Analysis: –Develop methods to analyze multi-site fMRI data Tools: –Develop a scalable IT application toolkit to support multi-site fMRI studies Dissemination: –Make the tools, procedures, and collected datasets widely available

User Query FIPS Results FMRI Images Automated Image Upload to SRB/HID for sharing FIPS: FSL Image Processing Scripts FBIRN Neuroinformatics Vision HIDB SRB/ Local fMRI Scanner Clinical Data Computer Aided Scale Input (CALM/GAME) Clinical Data Entry Interface URL links fMRI Scanner

Demographic Information Diagnostic Group SchizophreniaHealthy Volunteers N with images5360 Female/Male21/2727/29 Age (years)

Significant Main Effect of Diagnosis: AudOdd with Smooth To

Site effects minimized

MAGH ICA of Phase I Data

Novel analysis developments: fMRI Activation Pattern Spatial correlation of activation across voxels –bell shapes in local regions location of the activation centers size of peak activations area of the local activation cluster Beta Coefficients Whole brain 2D slide of β-map (Sensorimotor task) Thresholded results (incomplete) Surface results

QA Tool Summary into HID

Summary of Analysis Achievements Implementation and testing of a NIfTI compatible fBIRN image analysis pipeline (FIPS) Completion of a multicenter image upload and processing cycle using SRB, BIRN upload and download tools, fBIRN data base, fBIRN file structures, and fBIRN processing tools Significant progress in completing quality assurance analyses of Phase II images Initiation of multicenter analyses aimed at testing clinical hypotheses about abnormal brain function in schizophrenia.

The FBIRN Aims Calibration: –Assess and correct for the major sources of multi-site variation Cognitive Tasks: –Develop robust protocols for multi-site fMRI studies Analysis: –Develop methods to analyze multi-site fMRI data Tools: –Develop a scalable IT application toolkit to support multi-site fMRI studies Dissemination: –Make the tools, procedures, and collected datasets widely available

21 …………… Scrambled images Negative distracters Neutral distracters Memoranda Forced Choice ………… Working Memory for Words Design

22 Blah Duke 3T n=23 learn distract retrieval

23 View L VOTC

24 Robustness of ‘modes’

The FBIRN Aims Calibration: –Assess and correct for the major sources of multi-site variation Cognitive Tasks: –Develop robust protocols for multi-site fMRI studies Analysis: –Develop methods to analyze multi-site fMRI data Tools: –Develop a scalable IT application toolkit to support multi-site fMRI studies Dissemination: –Make the tools, procedures, and collected datasets widely available

27 The Effect of Adjusting for Site Differences in Signal-to-Noise-Ratio (Temporal) Friedman, Glover & The FBIRN Consortium, 2006 (Nov), NeuroImage

No calCalib 3.5 ≤ t ≤ 10 vol = p.001vol = 1.0 BH Calibration: Group Activation M. Thomason et al. 2006

BH Calibration: Inspiration control no control w/control

CBF can effect the amplitude & shape of the BOLD signal

ASL- quantitative rCBF maps

Selected Highlights Only Be sure to see the posters in the Hall

The FBIRN Aims Calibration: –Assess and correct for the major sources of multi-site variation Cognitive Tasks: –Develop robust protocols for multi-site fMRI studies Analysis: –Develop methods to analyze multi-site fMRI data Tools: –Develop a scalable IT application toolkit to support multi-site fMRI studies Dissemination: –Make the tools, procedures, and collected datasets widely available

Dissemination Web tutorials available: More tools and data available for download: FBIRN Traveling Subjects Dataset (Phase I): Deidentified versions of the imaging and demographic datasets, now with behavioral data of all subjects from many sites E-prime Programs used in data collection (Phase I and Phase II): –The SIRP, MMN, Rest, Breathhold, Sensorimotor tasks, the Auditory Calibration and Reaction Time tasks for both Phase I and Phase II

Dissemination FIPS 1.0 available with documentation and a training dataset Updated BXH/XCEDE tools suite External Collaborations: US: TURNS International: Phase 2 tools and paradigms to Italy, Norway and China

Invited presentations and abstracts this year Calhoun, V.D., "Independent Component Analysis of BOLD fMRI Data" for ISMRM Educational Course on "Multi-Modal fMRI: Physiology, Acquisition, and Analysis", May Turner, J.A. (2006). Calibration strategies to improve data comparability. Optimizing fMRI approaches to Adolescent Mental Disorders, NIMH Workshop, August 17-18, 2006 Potkin, S.G. (2006). The Integration of Brain Imaging and Genetics: A Strategy to Study Neuropsychiatric Disease. University of Utah, Grand Rounds, September 5, Yendiki, A., Wallace, S, Vangel, M., Clark, V., Lim, K.O., Andreasen, N., Greve, D., Manoach, D.S., Gollub, R.L. (2006). Multi-site characterization of an fMRI working memory paradigm: Reliability of activation indices. Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, Kilpatrick, L.A., Fallon, J., Turner, J.A., Kennedy, J., Macciardi, F., Potkin, SG. (2006). Genetic Impact on Dorsolateral Prefrontal Functional Connectivity in Schizophrenics During a Working Memory Task. Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, Turner, J.A., Stern, H., Friedman, L., Brown, G., Greve, D., Glover, G.H., Wible, C., Potkin, S.G., FBIRN. (2006) Variance reduction in multi-site functional imaging. Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, Keator, D.B, Grethe, J., Ozyurt, B., Gadde, S., Wei, D., Turner, J.A., Potkin, S.G., Brown, G.G., McCarthy, G., Glover, G.H., Stern, H., Lauriello, J., Friedman, L., Belger, A., Lim, K.O., Pieper, S., Greve, D., FBIRN. (2006). Function Biomedical Informatics Research Network (FBIRN) Open Source FMRI Informatics, Calibration, and Data Tools Repository. Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, Keator, D.B., Ozyurt, B., Wei, D., Gadde, S., Potkin, S.G., Brown, G., Morphometry BIRN, FBIRN., Grethe, J. (2006). A General and Extensible Multi-Site Database and XML based Informatics System for the Storage, Retrieval, Transport and Maintenance of Human Brain Imaging and Clinical Data. Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, Polina Goland. Anatomically-Guided MRF Spatial Regularization Model for fMRI Detection. (Using FBIRN Phase I data) Annual Meeting of the Organization for Human Brain Mapping, Florence, Italy, June 11-15, 2006.

Manuscripts and Publications This Year Thomason, M.E., Foland, L.C, and Glover, G.H. (2006) Calibration of BOLD fMRI using breath-holding reduces group variance during a cognitive task. Human Brain Mapping, in press. Friedman L, Glover GH (2006) Report on a Multicenter fMRI Quality Assurance Protocol. Journal of Magnetic Resonance in Imaging, 23: Brown, GG and Eyler, LT. (2006) Methodological and conceptual issues in functional magnetic resonance imaging: Applications to schizophrenia research. Annual Review of Clinical Psychology, Vol. 2: Friedman L., Glover GH, Krenz D, Magnotta V. FIRST BIRN. (2006). Reducing Scanner-to-Scanner Variability of Activation in a Multi-center fMRI Study: Role of Smoothness Equalization. Manuscript submitted. Friedman, L., FBIRN. (2006). Intra-Scanner and Inter-Scanner Reliability in a Multicenter fMRI Study. Manuscript submitted. Friedman L., Glover GH, FIRST BIRN. (2006). Reducing Scanner-to-Scanner Variability of Activation in a Multi- center fMRI Study: Controlling for Signal-to-Fluctuation-Noise-Ratio (SFNR) Differences. Neuroimage, in press. Lee, C.P., Dourish, P., Mark, G. (2006). The Human Infrastructure of Cyberinfrastructure. Manuscript in press. Kim, S, Smyth, P, Stern, H. (2006). A nonparametric Bayesian approach to detecting spatial activation patterns in fMRI data. Proceedings of the 9th International Conference on Medical Image Computing and Computer- Assisted Intervention (MICCAI), October Kim, S, Smyth, P. Hierarchical Dirichlet processes with random effects. Advances in Neural Information Processing 19, in press. Zou, KH, Bhagwat, JG, Wu, IY, Wells, WM, Jolesz, FA, Black, PM, Kikinis, R, Ohno-Machado, L, Talos, I. Statistical Designs of Neuroimaging Studies via Retrospective and Prospective Sample Size Calculations: An illustration on MR Guided Neurosurgery and Functional MR Imaging. Submitted to Academic Radiology special issue.

FBIRN Plans Continue New and better multi-site Calibration methods –Using BH improvements –Using ASL Broader multi-site Cognitive tasks –Efficient, combined tasks –Activating emotional and cognitive circuits, and interactions Improved multi-site Analysis methods and tools Publicly available, mediated datasets for queries and analysis