Noninvasive monitoring of breast cancer during neoadjuvant chemotherapy using optical tomography with ultrasound localization

Abstract

The purposes of this study were 1) to investigate the feasibility of using optical tomography in the near-infrared (NIR) spectrum combined with ultrasound (US) localization (NIR/US) in monitoring tumor vascular changes and assessing tumor pathological response during chemotherapy and 2) to compare the accuracy of NIR/US with magnetic resonance imaging (MRI) in predicting residual cancer after neoadjuvant chemotherapy. Eleven female patients were studied during treatments with a combined imager consisting of a commercially available US system coupled to an NIR imager. Contrast-enhanced MRI was performed before treatment and surgery. Tumor vascular content was assessed based on total hemoglobin concentration and volume obtained from NIR data. A percentage blood volume index (%BVI) was calculated as the percentage ratio of the product of total hemoglobin concentration and volume normalized to pretreatment values. At treatment completion, pathologic assessment revealed three response groups: complete or near-complete responders (A), partial responders (B), and nonresponders (C). The mean %BVIs of groups A, B, and C at the treatment completion were 29.1 +/- 6.9%, 46.3 +/- 3.7%, and 86.8 +/- 30.1%, respectively (differences statistically significant, P < .04). At the end of cycle 2, the %BVI of group A was noticeably lower than that of the partial (P = .091) and nonresponder groups (P = .075). Both NIR/US and MRI were equally effective in distinguishing different response groups in this pilot study. Our initial findings indicate that NIR/US using %BVI can be used during chemotherapy to repeatedly monitor tumor vascular changes. NIR/US also may evaluate pathologic response during treatment allowing for tailoring therapies to response.

Figures

Figure 1

Combined US and NIR systems and a hand-held probe with a centrally located US linear array and NIR source-detector fibers distributed at the periphery of the probe.

Figure 2

%BVI obtained from complete/near-complete responder group A, partial responder group B, and nonresponder group C at the end of cycle 2 (blue bars) and before surgery (red bars).

Figure 3

Ultrasound images of a high-grade infiltrating ductal carcinoma (patient 1) obtained before treatment (a1), at the end of cycle two (a2), and before her surgery (a3). US images showed dramatic reduction of tumor size from 4.4 cm to a smaller area visible with the assistance of a metallic marker placed before chemotherapy. (b1) to (b3) are the corresponding tHb maps. In each tHb map, seven slices correspond to spatial images of 9 cm x 9 cm obtained starting at 0.5 cm underneath the skin surface to 3.5 cm deep toward the chest wall with 0.5 cm spacing in depth. The color bar in tHb map is in units of micromoles per liter. The tHb map showed a heterogeneous pattern before treatment and was more confined to a much smaller core area at the end. (c) is a postcontrast CT scan before initial treatment showing a lobulated tumor. (b4) displays the %BVI computed from the NIR hemoglobin images at the three treatment points with the first point measured before treatment as the baseline. The %BVI dropped to 32.1%. This patient received near-complete pathologic response.

Figure 4

US images of a high-grade infiltrating ductal carcinoma (patient 3). (a1) to (a3) are US images acquired the same day before initial treatment, at the end of cycle 2, and before definitive surgery, respectively. US images showed significant reduction in tumor volume at the end of cycle 2. (b1) to (b3) are corresponding tHb concentration maps. In each tHb map, seven slices correspond to a spatial image of 9 cm x 9 cm obtained starting at 0.2 cm underneath the skin surface to 3.2 cm deep toward the chest wall with 0.5 cm spacing in depth. A 62.5 µM/l reduction in hemoglobin level was obtained at the end of the treatment and the corresponding %BVI dropped to 21.1% (b4). (c1) to (c2) are postcontrast subtracted MRI images acquired before initial treatment and before definitive surgery, respectively. MRI image revealed no tumor mass at the end of the treatment. This patient received a complete pathologic response.

Figure 5

US images of a low-grade infiltrating ductal carcinoma (patient 11) shown in the left column of (a1) to (a5). The tumor margins shown in the first three US images were not well defined but were better delineated in the last two images (88% reduction from pre- to posttreatment). The middle column of (b1) to (b5) shows corresponding hemoglobin maps from pretreatment (b1) to posttreatment (B5), which reveal substantial blood volume near the chest wall (third slice) throughout the treatment. In each tHb map, seven slices correspond to spatial a image of 9 cm x 9 cm obtained starting at 0.2 cm underneath the skin surface to 3.2 cm deep toward the chest wall with 0.5 cm spacing in depth. (b6) plots the corresponding %BVI from baseline to preoperative assessment every two cycles and no reduction in %BVI was observed. The left column shows postcontrast subtracted MRI images of pretreatment (c1) and posttreatment (c2), respectively. Volume reduction from MRI images is 16%. This patient received a mastectomy and the pathologic residual tumor was 3.3 x 2.8 x 1.2 cm extending to the skin and pectoralis muscle.

Figure 5

US images of a low-grade infiltrating ductal carcinoma (patient 11) shown in the left column of (a1) to (a5). The tumor margins shown in the first three US images were not well defined but were better delineated in the last two images (88% reduction from pre- to posttreatment). The middle column of (b1) to (b5) shows corresponding hemoglobin maps from pretreatment (b1) to posttreatment (B5), which reveal substantial blood volume near the chest wall (third slice) throughout the treatment. In each tHb map, seven slices correspond to spatial a image of 9 cm x 9 cm obtained starting at 0.2 cm underneath the skin surface to 3.2 cm deep toward the chest wall with 0.5 cm spacing in depth. (b6) plots the corresponding %BVI from baseline to preoperative assessment every two cycles and no reduction in %BVI was observed. The left column shows postcontrast subtracted MRI images of pretreatment (c1) and posttreatment (c2), respectively. Volume reduction from MRI images is 16%. This patient received a mastectomy and the pathologic residual tumor was 3.3 x 2.8 x 1.2 cm extending to the skin and pectoralis muscle.

Figure 6

MVD counted from anterior and deep surgical blocks of residual tumor specimens versus tHb maximum values measured at the top and deeper layers in the tHb images. The correlation coefficient of linear regression curve is 0.46, which is moderately significant (P = .0561).