PURPOSE To investigate prospectively the feasibility of using optical tomography with ultrasonographic (US) localization to differentiate malignant from benign breast masses and to compare optical ...

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. 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. 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 micromol/l 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). 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.

Indocyanine green (ICG) as a fluorescent agent has been widely used in biomedical fields since its introduction.^{1 2 3 4 5} ICG has attractive features of very low toxicity and high absorptance in a wavelength range of 600 to 900 nm, which is a relatively transparent window for biological tissues. It is well known that the absorption and emission properties of ICG are affected by the concentration of ICG and the solvent in which ICG is dissolved.^{3 4 5} In a dilute aqueous solution, an absorption peak at the wavelength of 780 nm and an emission peak at the wavelength of 830 nm were observed. With the increasing ICG concentration, the absorption peak shifts to the wavelength of 695 nm.^{1 3 4 5 6 7} This shift of absorption peak is attributed to aggregation of ICG molecules from monomer to oligomer. Absorption and emission properties of ICG in other solvents, such as plasma and human serum albumin (HSA), are different from those in aqueous solution.^{3 4 5 6 7} These odd optical characteristics make ICG intriguing to investigators.^{3 4 5}

A novel two-step reconstruction scheme using a combined near-infrared and ultrasound technique and its utility in imaging distributions of optical absorption and hemoglobin concentration of breast lesions are demonstrated. In the first-step image reconstruction, the entire tissue volume is segmented based on initial coregistered ultrasound measurements into lesion and background regions. Reconstruction is performed by use of a finer grid for lesion region and a coarse grid for the background tissue. As a result, the total number of voxels with unknown absorption can be maintained on the same order of total measurements, and the matrix with unknown total absorption distribution is appropriately scaled for inversion. In the second step, image reconstruction is refined by optimization of lesion parameters measured from ultrasound images. It is shown that detailed distributions of wavelength-dependent absorption and hemoglobin concentration of breast carcinoma can be obtained with the new reconstruction scheme.