Utilizing Optical Tomography with Ultrasound Localization to Image Heterogeneous Hemoglobin Distribution in Large Breast Cancers

PURPOSE: Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Noninvasive imaging that can monitor angiogenesis may be invaluable initially for diagnosis and then for assessing tumor response to treatment. By combining ultrasound (US) and near-infrared (NIR) optical imaging, a reliable new technique has emerged for localizing and characterizing tumor angiogenesis within the breast. METHODS: This new technique employs a commercial US transducer coupled with an array of NIR optical fibers mounted on a hand-held probe. The US image is used for lesion localization and for guiding optical imaging reconstruction. Optical sensors are used for imaging tumor total hemoglobin distribution, which is directly related to tumor angiogenesis. RESULTS: Six large breast carcinomas were studied and microvessel density count was then performed on tissue samples obtained from these cancers. Two patients had locally advanced breast cancers and received neoadjuvant chemotherapy for 3 months. In one patient, before chemotherapy, the total hemoglobin distribution showed a high concentration at the cancer periphery; the distribution was later confined to the core area after 3 months of treatment. In another patient, as treatment progressed, the maximum hemoglobin concentration decreased from 255.3, to 147.5, to 76.9 wmol/I with an associated reduction in spatial extension. The other four patients had cancers of 2.0 to 3.0 cm in size and were imaged either at the time of core biopsy or definitive surgery. The histologic microvessel density counts from these tumor samples correlate to hemoglobin distributions with a correlation coefficient of 0.64 (P < .05). CONCLUSION: These initial results suggest that this new imaging technique may have great potential in imaging the heterogeneous vascular distribution of larger breast cancers in vivo and in monitoring treatment-related changes in angiogenesis during chemotherapy.