1. Qianqian Fang, Stefan Carp, Mark Martino, Richard Moore, Daniel Kopans, David Boas Optics Division, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School NIH R01-CA97305, R01-CA142575 3D OPTICAL IMAGING AND DIGITAL XRAY OF BREAST LESIONS HbT TOMO slice μMμM A F T A F T Fang et al Radiology 2011

2.  Background  Motivation and goal  A multi-modality approach  Technology development  Combined optical and tomosynthesis imaging system  Multi-modality imaging data analysis  Clinical trials and findings  Imaging healthy subjects  Imaging malignant and benign lesions  Statistical group analysis  Conclusions Outline

3. Second leading cause of death for women in the US Accounting for 15% female cancer death Early detection is critical Breast cancer fact sheet

4. Complex nature of diseases requires more diagnostic information Combine structural and functional imaging http://en.wikipedia.org/wiki/Positron_emission_tomography Multi-modality Imaging Optical & Mammography PET & CTPET & MRI

5. Position breast Compress Take optical measurement (45s)‏ Remove optical probes Take DBT scan (2s)‏ Duration: Approx 90s Multiplexed RF lasers: 40 (685/830nm) Multiplexed CW lasers: 150 positions (685/810/830nm) Frequency-encoded (FE) CW lasers: 26 (685/830nm) For 45 seconds: we run all FE CW at 20Hz, 7 repetitions for 22 MUX CW positions and 2 repetition for RF Tomographic Optical Breast Imaging Digital Breast Tomosynthesis Combined TOBI & DBT system Spatial vs. Temporal Resolution

6. Motivation for dynamic imaging Signal level drops up to 10% during 45 seconds of measurement Dynamic process leads to increased absorption Signal Intensity (A.U.) 0 20 40 60 Time (s) Signal Intensity (A.U.) 0 20 40 60 Time (s) Signal Intensity (A.U.) 0 20 40 60 Time (s)

7. Processing pipeline DBT Image reconstruction Optical/X-ray Registration Mesh generation Optical Image reconstruction 15 Projections over ±22.5° (MLEM Recon)

8. Processing Pipeline DBT Image reconstruction Optical/X-ray Registration Mesh generation Optical Image reconstruction

9. Processing Pipeline DBT Image reconstruction Optical/X-ray Registration Mesh generation Optical Image reconstruction

10. Processing Pipeline DBT Image reconstruction Optical/X-ray Registration Mesh generation Optical Image reconstruction

11.  Background and significance  Motivations and goals  A multi-modality approach  Technology development  Combined optical and tomosynthesis imaging system  Multi-modality imaging data analysis  Clinical trials and findings  Imaging healthy subjects  Imaging malignant and benign lesions  Statistical group analysis  Conclusions Outline

12. Sample optical images – Healthy I 37 yr old woman, right breast Fang Q, et al.,” IEEE Trans. Medical Imaging, vol. 28, issue 1, pp. 30 – 42, Jan. 2009. TOMO slice HbT C F A C F A Spatial vs. Temporal Resolution

13. TOMO sliceHbTStO 2 Scat. Coeff (830nm)‏ fibroglandular/adipose: 1.42 1.02 1.28 μMμM 1/cm C F A C F A C F A C F A Sample optical images – Healthy I 37 yr old woman, right breast

14. 45 yr old woman, right breast 2.5 cm IDC with a large portion of DCIS StO 2 Scat. Coeff (830nm)‏HbT TOMO slice μMμM 1/cm fibroglandular/adipose: 1.55 1.00 1.04 tumor/adipose: 2.07 0.99 1.09 A F T A F T A F T A F T Reconstructed images – Malignant

15. Age=79, L-side IDC, 2.5cm Age=77, R-side IDC grade 3, 0.7cm Age=42, L-side 2cm mass (invasive mammary carcinoma)‏ Age=45, R-side, IDC 2.5cm More malignant lesions (HbT Images)

16. ROI analysis and statistical tests

17. 42 years old woman: 8mm fibroadenoma Solid Benign Lesions: Fibroadenomas HbT (μM) 39 years old woman: 16mm fibroadenoma HbT (μM)

18. Left breast of a 49-year-old woman Two cysts 29x11x26mm and 12x9x5mm at the pointed locations Benign Lesions: cysts (μM) 1/cm TOMO sliceHbTStO 2 Scat. Coeff (830nm)‏

19. ROC – Malignant vs Benign AUC = 0.74 AUC = 0.75 n=25 n=8 n=17 Structural priors in Optical Imaging Reconstruction Spatio-Temporal Resolution Novel Biomarkers from Dynamics

20. ROC – Cyst vs Malignant AUC = 0.83 AUC = 0.86 Impact patient work flow for follow-up US

21. Compositional Prior Fang BOE 2010 DBTCfHbT binaryHbT normal HbT Compositional Prior

22. Compositional Prior Fang BOE 2010 DBTHbT compHbT normal DBTHbT compHbT normal Prior improves symmetry of optical properties between left and right breasts! Residual comparable or reduced… degeneracy of ill-posed reconstruction

23. StO 2 Scat. Coeff (830nm)‏HbT TOMO slice μMμM 1/cm A F T A F T A F T A F T Compositional Prior - Tumors Still only 2 components – Fibroglandular and Adipose Stats about the same as without prior

24. Compositional Prior - Tumors Add a 3 rd component, a gaussian sphere for Lesion HbT 2 Component HbT 3 Component 2 Component 3 Component

25. Summary HbT TOMO slice μMμM A F T A F T Signal Intensity (A.U.) 0 20 40 60 Time (s) HbT differentiates malignant from benign SO 2 & HbT differentiates Cysts Composition Priors expected to offer improvements 60 more lesion cases being analyzed now! 2 nd Generation with TechEn Inc. and Philips Medical (NIH AIP and Mass Life Science Center)