2004 All Hands Meeting

Welcome to the BIRN All Hands Meeting

Welcome

Thanks to • BIRN-CC, • Local organizers from MGH • The Crossover Working Group

Welcome

NCRR• Mike Marron• Anthony Hayward

BIRN-CC• Mark Ellisman

Testbed PI introductions

Why are we here?

BIRN-CC: Central infrastructure Mouse BIRN: Animal models of human disease BIRN-CC and Mouse BIRN reports this morning

Function and Morphometry BIRN: Human diseases• Alzheimer’s Disease• Schizophrenia

Alzheimer’s Disease Affects a third of those over age 75 Progressive degenerative illness Loss of memory, ability to plan and

think Loss of activities of daily living and

develop troublesome behavior leading to institutionalization

Third most expensive illness A family illness with enormous

economic and social costs

AP = amyloid plaques; NFT = neurofibrillary tangles; Slide courtesy of: George Grossberg, M.D.; St. Louis University

Neuropathological ChangesNeuropathological ChangesCharacteristic of ADCharacteristic of AD

Normal

AP

AD

NFT

Impact of delaying onset of Alzheimer’s disease in USA

Adapted from: Brookmeyer R et al. Am J Public Health. 1998; 88: 1337–42

16

Delay (years)

12

8

4

0205220422032202220122002

0

1

5

Pre

vale

nc

e A

D

(millio

ns

)

AD = Alzheimer’s disease

Course of aging: MCI & ADCourse of aging: MCI & AD

AAMI

MCI

Clinical AD

Time (years)

Co

gn

itiv

e d

eclin

e ‘Brain’AD

Brain ageing Mild

Moderate

Moderately severe

Severe

AAMI = age-associated memory impairment; MCI = mild cognitive impairment

Distinguish other diagnoses

30 Nondemented Subjects with ApoE4 or E3 Allele

ApoE4 Genotype and Brain ApoE4 Genotype and Brain Activation Activation

Ch

a ng

e i n

Sig

na l

In

ten

s it y

(%

)

Trial Number

1.6

-0.46

-0.20.00.20.40.60.81.01.21.4

54321

ApoE4

ApoE3

Bookheimer SY,, et al. N Engl J Med. 2000(Aug 17);343(7):450-456

The Development of SchizophreniaThe Development of Schizophrenia

Sheitman BB, Lieberman JA. J Psychiatr Res. 1998(May-Aug);32(3-4):143-150

Age (Years)

Good

Function

Poor15 20 30 40 50 60 70

Premorbid Progression StableRelapsing

Pro

dro

me

?Improving

•

Fir

st

Ep

isod

e

Working Memory in SchizophreniaWorking Memory in Schizophrenia

Sternberg task: Sternberg task: Five Five Two Two

5 6 2 8 1

+

8

+

3

Five items compared to Two

0 9

+

6

+

9

Genomics and Human Brain FunctionGenomics and Human Brain Function

Clinical and cognitive measures

NeuroimagingInheritedgenotype

DNA

-48-48 AA

3’3’5’5’--

3’3’5’5’-- -48-48

GG

DRD1

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

5 6 2 8 1

+

8

+

3

5 6 2 8 15 6 2 8 1

++

88

++

33

Why are we here?

A concerted effort is required To achieve more in synergy than as multiple

uninvolved efforts This is a new way to do science

• Is it a useful one?• Is the whole greater than the sum of its parts?

Infrastructure development

Data sharing is essential and requires infrastructure Terabytes of data are not amenable to ftp or mail Data has to be meaningfully combined to generate

new findings that would not otherwise be possible

Clinical Measures

GenotypeData

Local Storage

DU

P

HumanData

Protection

INSTITUTION A

BIRN Rack

SRBMCAT

HID

PortalMediator

Calibration& Analysis

Tools

GridFederation: distributed DB, autonomous, access integrated resourcesMediator: translates heterogeneous data sources to consistent representation

ImagingData

Infrastructure development

We need resources to support this scientific strategy• The Shared Resource Broker (SRB)• A federated database system• Intelligent queries of nonlocal, integrated data,etc

The resources we develop are applicable beyond the original testbed intentions• U54s, etc., MIND, TURNS, CATIE, NTROI, industry• GCRC interactions

A new way of studying diseases

Cooperation among top competitors• How to share, work, glory and $

• Who makes and keeps the rules

Integrative and synergistic

A new way of studying diseases

Multidisciplinary research: • Researchers working in parallel, in sequence, or jointly on

a common problem maintaining a discipline-specific basis.

Transdisciplinary: • Bridging several fields • Develop a shared conceptual framework formed by

integrating and synthesizing discipline-specific theories, and perspectives to address a common problem

• Such that the whole is more than the sum of its parts (Rosenfield, 1992).

A new way of studying diseases

This meeting is an invaluable opportunity to enrich your own research• Collaborating with top researchers around the

country and • Developing novel methods across disciplines

What can the other test bed tools, methods, and findings offer you?

What of your methods and findings might enhance their research?

Today: Testbed Discussions

BIRN-CC (9:30 am) Mouse BIRN (10:45 am)

Morph BIRN (1:45 pm) Function BIRN (2:45 pm)

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

Today: BIRN Development

New initiatives involving BIRN (4:15 -5:00)• Four NCRR U54 funded and two directly involve BIRN• Roadmap Exploratory Center for Imaging Genetics• ADNI, etc…

Cross-testbed interactions & coordination (5:00- 6:00)• Information sharing, exploration of cross-test beds syngery• Eg. Can Mouse use Morphometry’s Slicer?• Eg. How FBIRN use Mouse registration tools?

Tomorrow: Steering the BIRN Future

Genetics: Its promise and challenge

(8:30-10:00)

Task Force discussions: (10:30-3:30)• Other institutions, investigators want access to the data

and resources This challenges current data sharing methods and policies This requires clear IP and human subjects’ protections This has IT resource implications and demands

• Given our experiences so far: How do we enable this access?

• This is an All-BIRN issue: these decisions affect YOU

Tomorrow: Where do we go now?

Providing BIRN toolkit and data, aka: Do you know where your portal is? (3:30 – 4:30 pm)

• What are the resources and tools currently available, developed by BIRN-CC and all the test beds

• How do you use these tools now?• What are the current plans for future developments

Milestones for the next year (4:45 – 6:00 pm)

• How is the whole greater than the sum of the parts• Does this infrastructure being created allow discovery of

new, integrated findings based on the collaborative synergy of BIRN?

Also not to be missed

Executive Committee meetings • Noon-2 pm each day

FBIRN Image Processing Pipeline Working Group meeting • Noon Today in the Nantucket Room

Mediator hands-on demos • Noon Tomorrow in the Nantucket Room

FBIRN Statistics Discussion • Noon-3 pm Tomorrow in the Quincy Room