Optical assessment of tumor resection margins in the breast

Abstract

Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.

Fig. 1

Photomicrographs of H&E-stained breast tumor margin sections, representative of (A) invasive ductal carcinoma extending the full length of the margin (positive) (B) at ~1mm from the surgical margin (close) and (B) greater than 2 mm from the inked surface (negative).

Fig. 2

Distribution of single margin areas observed in 120 BCS patients.

Fig. 3

Schematic of the clinical instrument and the fiber arrangement of the multi-channel probe. Each channel has 4 (200 μm) collection fibers and a central bundle of 19 (200 μm) illumination fibers. All 8 channels are arranged in a 4×2 array with a separation distance of 10 mm (center to center).

Fig. 4

A) Photograph of the multi-channel fiber optic probe in an aluminum adaptor to space each of the 8 probes 10 mm apart in a 2 × 4 configuration, and the two pieces of the plexi-glass box, B) Photograph of a mockup of a lumpectomy specimen being imaged in the plexi-glass box. The two pieces of the box slide together to hold the specimen in place and the probe is placed in contact with the specimen via the holes in the box.

Fig. 5

Representative results from the clinical study, showing results from a pathologically-confirmed negative margin. These screenshots depict the β-carotene:< μs′> (left) and total hemoglobin:< μs′> (right) maps, as well as the corresponding histograms for these images. The percentage of image pixels below the pre-defined thresholds are indicated in this histogram insets, and the corresponding predicted margin diagnosis is indicated at the bottom of the screen. Path-confirmed cancer-free pixels are indicated with white circles.

Fig. 6

Representative results from the clinical study, showing results from a pathologically-confirmed positive margin (IDC). The black circles indicate pixels which were confirmed to contain residual invasive ductal carcinoma, whereas white circles indicate pixels which were confirmed to be free of residual cancer.

Fig. 7

Boxplots of image-descriptive variables with highest diagnostic potential. A) Boxplot of percentage of β-carotene:< μ_s′> image pixels below 6 μM-cm, B) boxplot of percentage of total hemoglobin:< μ_s′> image pixels below 8 μM-cm. P-values from Wilcoxon rank-sum tests are given in the panels.