2004 FBIRN Meeting

FIRST BIRN: Challenges of Collaborative Multi-site, Multi-discipline Research

Steven Potkin, MD

Gary Glover, PhD

Gregory McCarthy, PhD

OutlineOutline

Why is this important Our vision Clinical Aims Challenges Accomplishments

Gary Glover: Calibration Experience

Gregory McCarthy: Cognitive Challenges

Why Is This ImportantWhy Is This ImportantWhy Is This ImportantWhy 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 MapStatistical Parametric MapMai et al Human Atlas, 2001Mai et al Human Atlas, 2001

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Why Is This ImportantWhy 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 DatabasesSolution: Queryable Federated Databases

fMRI

Are chronic, but not first-onset patients, associated with Are chronic, but not first-onset patients, associated with superior temporal gyrus dysfunction (MMN)?superior temporal gyrus dysfunction (MMN)?

IntegratedIntegrated ViewView

Receptor Density ERP

WebWeb

PubMed, Expasy

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Structure

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Clinical

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MediatorMediator

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-0.14-0.10-0.06-0.020.020.060.100.140.180.220.260.30

ARIP - 20MG ARIP - 30MG RISP - 06MG PLACEBOTreatment Group

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 AimsFIRST 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 PopulationsFBIRN: Patient Populations

Childhood schizophrenia Elderly onset First episode Chronic baseline and after treatment

• Atypical antipsychotic• Cognitive enhancers

Prodromal Normal healthy volunteers

First BIRN SitesFirst 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 CultureChallenges: 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 scientists Computer scientists• Experimental psychologists MRI physicists• Statisticians Database 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”

ChallengesChallenges

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 variabilityInter-site variability

Different scanners = different raw images

How bad it is?

Inter-site variabilityInter-site variability

Different scanners = different raw images

How bad it is?

A Unique Dataset: A Unique Dataset: Human Calibration SubjectsHuman 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 GUITechnology: HID GUI

Federated Imaging DatabasesFederated Imaging Databases

Solution: Federated DatabaseSolution: 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

WrapperWrapper

Wrapper

Structure

Wrapper

Clinical

Wrapper

MediatorMediator

0.150.18

0.140.11

-0.14-0.10-0.06-0.020.020.060.100.140.180.220.260.30

ARIP - 20MG ARIP - 30MG RISP - 06MG PLACEBOTreatment Group

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?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?