P2-10-09: Detecting Breast Cancer with Dynamic Diffuse Optical Tomographic Imaging.
Authors: Flexman ML , Kim HK , Lim E , Desperito E , Barbour RL , Hershman DL , Hielscher AH 
Published: June 2012

Background: Over the last decade diffuse optical tomography (DOT) has emerged as a novel medical imaging modality. Near-infrared light is used to non-invasively probe biological tissue, and three-dimensional (3D) maps of blood-dependent parameters can be obtained. Several studies are underway to show the clinical utility of DOT for imaging brain disease, joint disease, and breast cancer. Here we present the largest clinical study to date that uses hemodynamic effects caused by a simple breath hold to identify breast tumors using DOT.

Methods: We have designed and built a DOT breast imaging system that can acquire full 3D data sets within a fraction of a second. The system affords the ability to study fast hemodynamic effects in both breasts simultaneously. Using non-compressive imaging heads we measured the oxygenated and deoxygenated hemoglobin levels in the breasts of 15 patients whose mammogram showed a mass &gt;1 cm (4 benign, 11 malignant) and 3 healthy controls. Data was acquired over the course of a 30-second breath hold and 30 seconds thereafter. In addition, a baseline measurement of 30 seconds prior to the breath hold was obtained. A multi-wavelength image reconstruction algorithm was used to create 3D maps of hemoglobin-dependent parameters (Δ[HbO2] and Δ[Hb]) in the breast every 0.58 seconds, over the course of the 90-second experiment. An image analysis algorithm identified regions of peak percentage change in [Hb] and [HbO2] in the breast and then computed the average hemoglobin levels in those regions.

Results: We observed an increase in the hemoglobin levels in all breasts during the breath hold. Upon resuming breathing, these hemoglobin levels returned to baseline. Tumor bearing breasts showed a statistically significant slower return to baseline than healthy breasts. In particular, we found that tumors can be detected by a substantially larger Δ[Hb] value as compared to normal tissue in images acquired 15 seconds following the end of the breath hold. In 10 of 11 patients the malignant tumor was identified using this technique, suggesting sensitivity over 90%. No regions of increased Δ[Hb] were seen in the healthy breasts, or in the breasts with benign masses. The peak percentage change in [Hb] at the 15 second post-breath hold time point was 10.0 ± 6.0% (n=11) in the malignant tumors compared to 1.4 ± 0.5% (n=3) (p=0.001) in healthy patients and 4.8 ± 1.9% in benign masses (n=4)(p=0.03).

Discussion: A breath hold impedes venous return to the heart, which causes pooling of blood in the breast. This is observed as an increase in [Hb] and [HbO2] using DOT. Tumor vasculature is known to be more disorganized, tortuous, and leakier than normal vasculature. Therefore, once the breath hold is released and blood is allowed to drain from the breast, blood accumulated in the tumor during the breath hold will drain more slowly than blood in healthy tissue. This study has shown that DOT allows us to visualize these hemodynamic effects and use them to detect tumors with a simple breath hold and compression-free imaging head. Future studies need to explore the detection limits and general clinical utility of this technique for screening, differentiating malignant from benign masses, and treatment monitoring.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-09.