Design and Initial Testing of Imager for Simultaneous Bilateral Optical Mammography

1. Design and Initial Testing of Imager for Simultaneous Bilateral Optical Mammography OSA Biomedical Optics Topical Meeting April 13-17th, 2004 Miami, Florida Randall L. Barbour, Ph.D. SUNY Downstate Med. Ct., Brooklyn, NY

2. CONFLICT • NIRx Medical Technologies, LLC

3. Motivation for Time-Series Imaging • Basic Physiology: Tissue-Vascular Coupling • Oxygen delivery to tissue • Blood Volume • Blood Oxygenation • Regulation of vascular response • Neural, hormonal, metabolic • Vascular rhythms • Clinical Applications: Functional changes precede structural changes

4. Figure 1. Corrosion Cast of Tumor Vasculature. ‘tp’, = tumor periphery, ‘st’ = surrounding tissue. From Ref. , p. 16. Motivation for Time Series Breast Imaging Corrosion Cast of Tumor Vasculature

5. Technology Development

6. Approach to System Design • Goal: Systems that have turn-key functionality that are suitable for a range of applications. • Problem Areas • Data Collection. • Data Integrity. • Image Recovery. • Time-Series Image Analysis. • Image Display.

7. System Design Approach • Large dynamic range (109) • Variable framing rate (2 - 90 Hz) • Multiwavelength (2-4 color) • Automated set-up and control • Real-time visualization • System-data integrity checks • Custom configured measuring heads • Comprehensive software: • System control, image recovery, signal analysis, image display. • Integrated vital sign monitoring.

8. Time Series Optical Tomography Frame 1 2 3

9. SUNY DYNOT Breast Imager • Single, Dual Breast Measurement Heads • Time multiplexed DC Illumination • 32 source x 64 detector channels per breast. • 64 channel optical switch • 2-90 Hz framing rate • Advantage of Dual Breast Measurement: • - Provides for differential measurement!

10. Breast Measurement Heads Single Breast - Medieval Style Dual Breast - Madonna Style

11. Detector setup 830 nm 760 nm Detector setup Source fibers Source fibers Detector fibers Detector fibers RIGHT LEFT

12. Dual Breast Set-up Screen

13. Dual Breast Display Screen

14. CASE STUDIES

15. Healthy Tumor bearing 3 4 4 3 1 2 2 1 HbO2 Normalized detector reading Normalized detector reading Hb Time point Time point Tumor Detection by Response to Transient Hypoxemia

16. 1.00 0.75 0.50 0.25 Relative Contrast Tumor Figure 5. Right, 3D DYNOT image of tumor identifying imbalance in tissue oxygen supply/demand. Image was produced without need of contrast agents or compression. Left, sonogram image of same breast showing location of tumor. Note close agreement in size and location. Image of Transient Hypoxemia

17. Valsalva Maneuver

18. Vascular Response to Valsalva Maneuver

19. GLM Analysis: Percentage of Variance Accounted for by Model Function 100 50 1

20. P1: Left Breast P1: Right Breast 3 4 2 5 6 7 1 1.5e-8 0 -9.3e-9 2.1e-8 0 -1.2e-8 1st derivative of the deoxyhemoglobin image time series at indicated time points indicated along the Valsalva maneuver (1) (tumor-bearing patient: P1) 1 2 3 4 5 6 7 Ductal Carcinoma

21. 3 N1: Left Breast 4 2 5 6 7 N1: Right Breast 1 1.1 e-8 0 -1.46e-8 4.7 e-8 0 -1.1e-8 1st derivative of the deoxyhemoglobin image time series at indicated time points indicated along the Valsalva maneuver (2) (Healthy Volunteer) 1 2 3 4 5 6 7

22. Simultaneous Bilateral Measurements Look for differential responses in baseline and in response to provocation!

23. Baseline Comparisons Spatially averaged, low-pass filtered (0-0.38 Hz) total Hb (i.e., blood volume) baseline signals (left breast, right breast) Amplitude CSD Phase CSD

24. Spatially averaged, bandpass filtered (0.005-0.43 Hz) total Hb baseline signals Patient with active breast cancer: Baseline

25. Is the respiratory rhythm simply absent from the left breast? • No! Presence of respiratory peak in SD time series indicates that there is, instead, loss of coordinated activity in the breast at this frequency. • FT phase is spatially heterogen-eous, and contributions from all parts of the breast cancel out in the mean time series. Breast Cancer Patient Time-dependent, spatial standard deviation of bandpass filtered total Hb baseline signals CSD Phase of Mean time series

26. Bilateral Response to Valsalva: Healthy Subject

27. 1st Derivative Images for Deoxy Hb: Healthy Subject 2243 2305 2362 2292 2232 2277 Time Points

28. Time Point Left 2610 2634 2677 2700 2750 2818 3050 Right Bilateral Response to Valsalva: Cancer Patient Tumor

29. Summary • Developed a integrated measuring system capable of simultaneous bilateral time-series breast imaging. • Preliminary studies have shown evidence of characteristic changes to both baseline and response to provocation. • The form of these changes include disturbances in basal rhythms, and localized rates of change following a respiratory maneuver.

30. SUNY-NIRx Development Team • Key Personnel Degree Expertise Responsibility Randall Barbour Ph.D. Biochem, Lab. Med., Biomedical Optics PI Harry Graber Ph.D. Biophysics, Theory, Signal analysis Senior Appl. Specialist Yaling Pei Ph.D. Engineering, Numerical Methods, Algorithm Dev. Dir. Software Eng. Christoph Schmitz Ph.D. Physics, System design and integration Dir. Engineering David Klemer M.D., Ph.D. Int. Med., Elec. Eng., Application Development Medical Director Mikhail Levin Ph.D. Physics, Physical Optics Optical System Design Margarita Levin Ph.D. Physics, Physical Optics Sys. Testing, Validation Yong Xu Ph.D. Physics, Numerical Methods Algorithm Development Raphael Aronson Ph.D. Physics, Theory Adv. Theory Studies Nelson Franco M.D. Surgical Resident Breast Studies Rosemarie Hardin M.D. Surgical Resident Breast Studies Michael Katz M.D. Surgical Resident Limb Studies Alessandro Smeraldi M.D. Vascular Fellow (Staten Island U. Hosp) Limb Studies

31. Acknowledgements • NYS Department of Health • Army Research Office • NIH: NIBIB, NIHLB, NINDS, NCI, NIDDK

32. I look to THE DIFFUSION OF LIGHT and education as the resource to be relied on for ameliorating the condition, promoting the virtue, and advancing the happiness of man. — Thomas Jefferson (1822)