1. All Hands Meeting 2004 Title: Planned GCRC-BIRN Collaboration at BWH Jonathan Sacks, PhD

2. Quantitative perfusion analysis Methods - MRI protocol Absolute myocardial blood flows (MBF) (ml/min/g) at rest and during dipyridamole vasodilation were quantified by validated Fermi model deconvolution. Rest myocardial blood flow corrected for rate pressure product 6 segments at each endomyocardial and epimyocardial levels in each slice location Perfusion reserve (PR) = MBF during vasodilation MBF at rest Abnormal quantitative FPMP = Segmental endomyocardial PR significantly lower than matching epimyocardial PR by paired student t-test (p < 0.05)

3. Scenario One: Cardiac MR Cardiac research is being done at GCRC Under G. Adler M.D., PH.D., R. Kwong M.D. and others The study uses Cardiac MR to visualize blood perfusing through the heart. The purpose of the study is to determine whether treatment with an aldosterone receptor antagonist will improve myocardial perfusion in patients with diabetes mellitus. The image of the heart is divided into segments at each step in a time series. This enables blood perfusion to be visualized through time on each segment

4. Scenario One: Cardiac MR The Surgical Planning Lab (SPL) at BWH has over many years developed a set of tools for visualizing and analyzing MR images of the human brain and other organs. SPL is a participating site for both Morphometry and Function BIRN. These techniques provide superior resolution of MR images and many of them are automatic or semi-automatic If the techniques developed at SPL are applied to the study of blood perfusion in the cardiac study, very substantial gains in resolution and efficiency of computation are realized in comparison with current Cardiac MR

5. Scenario One: Cardiac MR One of the key requirements for tracking perfusion through a time series is registration of elements of the series with a baseline (the ‘first’ time slice) SPL has developed several registration techniques which are so accurate that it will be possible to track blood perfusion through a single voxel Segmentation using level sets, followed by ICP  Registration using non-linear warping  Spatio-temporal filtering

6. Scenario One: Cardiac MR  Alignment of anatomical models, MRI data and functional data from the CARTO system. Depicted here is simulated CARTO data and deidentified preoperative MRI data where the red dots show the position of the CARTO data points. The initial misaligned data (left) and the registration

7. Scenario One: Cardiac MR Figure 12. Ibrowser controller showing image intervals and controls for indexing and animating. name order visibility copy delete hold viewer FG viewer BG animation & viewing manual indexing

8. Figure 1. Generalized visualization and morphometric tools supporting FBIRN FLAC QA spatial processing activation detection data inspection morphometric interactive, multi-modality visualization report Interactive visualization tools DB  morphometric  functional  genetic  clinical  demographic … validation, reliability testing, population pooling activation detector suite … Interactive query for knowledge discovery Scenario One: Cardiac MR

9. fMRI AMPA Potentiator Study Design Baseline LY451395 (0.2 mg BID) or Placebo Scan 1 Scan 2 Scan 3 Week 0 Week 5 Week 9 Screening Visit -7 to -9 days LY451395 (1.0 mg BID) or Placebo

10. fMRI Block Design Paradigm Novel Face-Name Pairs Repeated Face-Name Pairs Novel Face-Name Pairs Repeated Face-Name Pairs 40s25s5s40s25s40s 25s5s +++ ++ Scenario 2: Alzheimer Study

11. LEAM fMRI  Thirteen AD subjects completed study with all three adequate fMRI scan sessions Eight subjects on MGH Siemens 3T (Trio) Five subjects on BWH GE 3T (long bore)

12. fMRI Block Design: Test-Retest Reliability in AD patient

13. Differences in prefrontal activation in LY451395 vs. placebo Session 3 > Session 1 for Drug (n=4) > Placebo (n=9)

14. GCRC: Gail Adler, MD, PhD Reisa Sperling Ray Kwong, MD Joe Ronda, MS Surgical Planning Lab, BWH: Ron Kikinis, MD Steve Pieper, PhD C.F. Westin, PhD Wendy Plesniak, PhD Acknowledgements