1. Temporal-Spectral Imaging of Functional States Randall L. Barbour NIRx Medical Technologies LLC SUNY Downstate Medical Center 4 th NIH Optical Imaging Workshop 2004

2. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Motivation Dynamic Optical Tomography – Natural vascular rhythms Arteries ~1 Hz Veins ~ 0.3 Hz Microvessels ~0.02 – 0.15 Hz – Varying metabolic demand influences tissue vascular coupling Response to provocation Influence of disease Effects of drugs Time series of images – Multiple features – High intrinsic contrast – No need for injection

3. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Motivation Dynamic Optical Tomography – Tumor detection / monitoring response to therapy – Diabetes (PVD) – Functional brain imaging – Small animal/pharmacological agents Value of intrinsic signals Instrumentation Analysis tools

4. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Vascular Dynamic States Non-propagating – Time varying local change (e.g., arterial HbO 2 ) – Pulsating behavior Propagating – Mayer Waves – Maneuver induced blood volume changes

5. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop 199920002001200220032004 1 st NIH Workshop OI: Dynamic OT sisi d i+c d i+j s i+j+c11 mcmc mjmj Symmetry based calibration Simultaneous dual-breast scan DYNOT at Photonic West DYNOT at Photonic West 1 st commercial DYNOT DYNOTcompact Evolving Technology – Milestones 1988/89: First description of Diffuse Optical Tomography 1995: First description of Diffuse Fluorescence Tomography NDM  Robust Solutions

6. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Integrated Imaging Platform System setup check 12 Real time display of raw readings

7. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Simultaneous Dynamic Dual Breast Measurements Healthy Breast – Coherent response to provocation Tumor Breast – Sluggish perfusion – Reduced response to natural effectors – Elevated Hb levels

8. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Dual Breast Measurement Head

9. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Simultaneous Dual Breast Measurement 12

10. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Dual Breast Imaging Result 1234567 1.5e-8 0 -9.3e-9 2.1e-8 0 -1.2e-8 Left (tumor) 1234567 Right (healthy)  Hbred [mol/l] Imaging frames

11. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Valsalva Maneuver Spatially averaged HbO 2 response Seconds 0 1500 Left Breast Right Breast 1- 0- 1- 0-

12. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Temporal Features for Valsalva

13. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Scatter Plot Analysis – Case 1 Right breast (healthy) Left breast (healthy) HbR HbO 2

14. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Scatter Plot Analysis – Case 2 Right breast (cyst) Left breast (healthy) HbR HbO 2

15. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Scatter Plot Analysis – Case 3 Right breast (healthy) Left breast (cystectomy) HbR HbO 2

16. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Scatter Plot Analysis – Case 4 HbR HbO 2 Right breast (tumor) Left breast (healthy)

17. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Information Content of Dynamic Behavior Amplitude changes Time delay, rate of change, … Directional features – Propagating behaviors, responses Mayer waves

18. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Tensor Imaging Time Frame n (small subregion of image area)  Spatial distribution of imaged property has moved between times n and n+1  Estimate magnitude of displacement  displacement  velocity  Find distances Δx and Δy for which f 2 (x+ Δx,y+ Δy) and f1(x,y) are most similar Time Frame n+1 Net displacement vector f1(x,y)f1(x,y) f2(x,y)f2(x,y)

19. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Object Size time

20. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Feature Propagation time

21. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Velocity Vector Fields

22. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Healthy Subject

23. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Diabetic Subject

24. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Things of Interest Temporal organization of vector fields Trajectories Duration Response to provocation, etc…

25. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Quantitative Performance of 1 st Order NDM ● NDM – 1 th Order Solution: FEM Model Spatial Correlation: 0.2456 Temporal Correlation: 0.9946 Reconstructed Images Targets X-Y Plane X-Z Plane Y-Z Plane

26. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Image Enhancement by Linear Deconvolution   ImageMedium ReconstructionFilter  MediumImage Reconstruction (a)(b)

27. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 1 2 3 4 5,... Step1 : Assign N independently known optical coefficient distributions where n is the number of mesh nodes. Temporal Encoding of Spatial Information Relative Amplitude

28. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Generation of Deconvolution Filter (2) Step2 : Simulate the detector readings and reconstruct the optical coefficient distributions using NDM: Step3 : Compute deconvolution filter : Known Distribution Reconstructed Distribution

29. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Temporal-Spectral Imaging Temporal Function Target X-Y Plane X-Z Plane Y-Z Plane 1 st Order NDM Without Deconvol. 1 st Order NDM With Deconvol.

30. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Image enhancement with noise t=0 t=T/4 t=T/2 t=3T/4 t=T X-Y Plane X-Z Plane X-Y Plane X-Z Plane X-Y Plane X-Z Plane (a) Before deconvolution and low-pass filter (b) After deconvolution and before low-pass filter (c) After deconvolution and low-pass filter Nosie level 2: 1%--10% Sinusoidal time series: T=10 s ● Images with noise:

31. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Summary Integrated, scalable technology Comprehensive software tools – System control, calibration – Data integrity – Image recovery, analysis, display Simultaneous multi-site monitoring Fast, stable reconstructions Exploration of varying forms of dynamic behavior – Amplitude, rate imaging – Tensor Imaging

32. 9/22/2004R.L. Barbour / NIH Optical Imaging Workshop Finding … ? …..Nemo!