2004 FBIRN Meeting FIRST BIRN: Challenges of Collaborative Multi- site, Multi-discipline Research Steven Potkin, MD Gary Glover, PhD Gregory McCarthy, PhD

Outline  Why is this important  Our vision  Clinical Aims  Challenges  Accomplishments Gary Glover: Calibration Experience Gregory McCarthy: Cognitive Challenges

Why Is This Important  Schizophrenia - Cause unknown No cure but treatable  Neuroimaging is critical to understanding Gross structural and functional abnormalities (e.g., frontal and temporal)

Statistical Parametric Map Mai et al Human Atlas, 2001 ?? ?? ?? ?? ?? ??

Why Is This Important  Research hampered by Spatial distortions (Morph BIRN) Inconsistent data & lack of replications Noncomparable imaging techniques Small and diverse patient populations

Solution: Queryable Federated Databases fMRI Are chronic, but not first-onset patients, associated with superior temporal gyrus dysfunction (MMN)? Integrated View View Receptor Density ERP Web PubMed, Expasy Wrapper Structure Wrapper Clinical Wrapper Mediator

 Functional Imaging Research Schizophrenia Testbed = First BIRN: Operational for 17 months  Builds on and extends the mouse BIRN and morphometry BIRN  Extend morphology BIRN technology Into 4D (time) During sensory and cognitive tasks Tackle schizophrenia

FIRST BIRN: Clinical Aims  Study brain functioning in schizophrenia with fMRI Dorsolateral pre-frontal cortex (working memory) Superior temporal gyrus (early cortical auditory processing) Site-specific cognitive tasks activating DLPFC and STG.  Develop infrastructure to understand the development & progression of schizophrenia  Sensitive to alteration by treatment

FBIRN: Patient Populations  Childhood schizophrenia  Elderly onset  First episode  Chronic baseline and after treatment Atypical antipsychotic Cognitive enhancers  Prodromal  Normal healthy volunteers

First BIRN Sites Brigham & Women’s Duke Iowa MGH Minnesota New Mexico UCI UCLA UCSD UNC Stanford Experienced imaging sites Well developed ideas on how imaging should be done

Challenges: Creating a New Culture  How to get competitors to cooperate Will this project decrease the RO1 $ pool How to share glory, work and $ Governance - who makes and keeps the rules  How to avoid “What’s mine is mine and what’s yours is mine”  How to communicate across fields efficiently: Clinician scientistsComputer scientists Experimental psychologistsMRI physicists StatisticiansDatabase engineers  How to show a clear scientific benefit from cooperation Efficiency of multiple studies in parallel; quick revisions Different perspectives create new ideas or achieve the lowest common denominator “designed by committee”

Challenges  How to incorporate HIPAA regulations Security - paperless/wireless & audit Confidentiality & IRB - what do subject need to know and agree to Rules of upload and down. access to data  How to develop a new model for data sharing  How to meet technological challenges: Space for storage Tools for manipulation Ability to transfer gigabytes of data around the country Assume that soft and hardware changes are inevitable  How to show usefulness outside of BIRN

Inter-site variability Different scanners = different raw images How bad it is?

Inter-site variability Different scanners = different raw images How bad it is?

A Unique Dataset: Human Calibration Subjects  5 healthy, right handed males  Between 18 and 40 years old  College students or graduates  Traveled around the country from late July to mid September, 2003  100 scanning sessions: over 800 different scans

Technology: HID GUI

Federated Imaging Databases

Solution: Federated Database fMRI Are chronic, but not first-onset patients, associated with superior temporal gyrus dysfunction (MMN)? Integrated View Receptor Density ERP Web PubMed, Expasy Wrapper Structure Wrapper Clinical Wrapper Mediator

Accomplishments: To Date  Common image translation method: XML  Common Database Schema for fMRI: HID (not yet federated)  Queryable clinical and imaging database: GUI  Initial phantom protocol and assessments: QA  Initial human calibration study  Analysis of same data with different methods  Initial calibration methods for multi-site fMRI studies  These methods are: Flexible, Expandable, and Adaptable to other types of data and fields of study

Major Accomplishments  Cultural change  A new way to do science that is both creative and exciting, and works Willingness to have others analyze your data with their methods To facilitate use of your methods on their data Sharing concepts as well as data Solving common problems –rapid turn around time, new perspectives

Why are we here today? WE NEED FEEDBACK FROM YOU:  Which developments are useful for your projects?  Which developments are we missing?  How can we build better bridges to your projects?