Rapid noninvasive optical imaging of tissue composition in breast tumor margins

Abstract

Background: In women undergoing breast conserving surgery (BCS), up to 60% can require re-excision. Our objective is to develop an optically based technology which can differentiate benign from malignant breast tissues intraoperatively through differences in tissue composition factors.

Methods: A prospective study of optical imaging of BCS margins is being performed. Optical images are transformed into tissue composition maps with parameters of total hemoglobin concentration, b-carotene concentration and scattering. The predicted outcome is then compared to the margin-level pathology.

Results: Fifty-five margins from 48 patients have undergone assessment. Within 34 specimens with pathologically confirmed positive margins, the ratio map of b-carotene/scattering showed the most significant difference reflecting a decrease in adipose and an increase in cell density within malignant margins (p=.002). These differences were notable in both in-situ and invasive disease.

Conclusions: We present a novel optical spectral imaging device that provides a rapid, non-destructive assay of the tissue composition of breast tumor margins.

Figure 1

A) Photograph of the portable optical spectral imaging device, and B) photograph of a mockup of a lumpectomy specimen being imaged by the handheld imaging probe of the device.

Figure 2

Maps of β-carotene:scattering coefficient for A) negative margin, C) margin positive for DCIS, E) margin positive for IDC. Site-level pathology for the margins indicated that the blue areas generally corresponded to cancer-free areas, whereas the red areas corresponded to regions with residual disease. Corresponding frequency histograms are given to the right of each map (B, D, F, respectively), and depict the distribution of β-carotene:scattering values present in each image. The vertical dashed line indicates the threshold on β-carotene:scattering values used in the predictive model to separate positive from negative margins; the percentage of image pixels below the threshold is given in the histogram inset.

Figure 3

Boxplots of A) percentage of pixels < 6 μM-cm β-carotene:scattering, and B) percentage of pixels < 8 μM-cm total hemoglobin:scattering, stratified by margin status (negative: blue, positive/close: red). P-values from Wilcoxon rank-sum tests are indicated in the plots.

Figure 4

ROC of the two predictors from Figure 3.

Figure 5

Maps of β-carotene:scattering coefficient (A, C) for margins positive for IDC but falsely classified as negative by the predictive model from 2 different patients. Corresponding frequency histograms are given to the right of each map (B and D, respectively), and depict the distribution of β-carotene:scattering values present in each image; the percentage of image pixels below the threshold is given in the histogram inset.