Optical scatter imaging of resected breast tumor structures matches the patterns of micro-computed tomography

Abstract

In patients undergoing breast-conserving surgery (BCS), the rate of re-excision procedures to remove residual tumor left behind after initial resection can be high. Projection radiography, and recently, volumetric x-ray imaging are used to assess margin adequacy, but x-ray imaging lacks contrast between healthy, abnormal benign, and malignant fibrous tissues important for surgical decision making. The purpose of this study was to compare micro-CT and optical scatter imagery of surgical breast specimens and to demonstrate enhanced contrast-to intra-tumoral morphologies and tumor boundary features revealed by optical scatter imaging. A total of 57 breast tumor slices from 57 patients were imagedex vivoby spatially co-registered micro-CT and optical scatter scanning. Optical scatter exhibited greater similarity with micro-CT in 89% (51/57) of specimens versus diffuse white light (DWL) luminance using mutual information (mean ± standard deviation of 0.48 ± 0.21 versus 0.24 ± 0.12;p < 0.001) and in 81% (46/57) of specimens using the Sørensen-Dice coefficient (0.48 ± 0.21 versus 0.33 ± 0.18;p < 0.001). The coefficient of variation (CV) quantified the feature content in each image. Optical scatter exhibited the highest CV in every specimen (optical scatter: 0.70 ± 0.17; diffuse luminance: 0.24 ± 01; micro-CT: 0.15 ± 0.03 for micro-CT;p < 0.001). Optical scatter also exhibited the highest contrast ratios across representative tumor boundaries with adjacent healthy/benign fibrous tissues (1.5-3.7 for optical scatter; 1.0-1.1 for diffuse luminance; 1.0-1.1 for micro-CT). The two main findings from this study were: first, optical scatter contrast was in general similar to the radiological view of the tissue relative to DWL imaging; and second, optical scatter revealed additional features associated with fibrous tissue structures of similar radiodensity that may be relevant to diagnosis. The value of micro-CT lies in its rapid three-dimensional scanning of specimen morphology, and combined with optical scatter imaging with sensitivity to fibrous surface tissues, may be an attractive solution for margin assessment during BCS.

Keywords: breast cancer; breast-conserving surgery; micro-CT; optical scatter imaging; spatial frequency domain imaging.

Figure 1.

Wide field-of-view images of representative invasive ductal carcinoma specimens (yellow arrows = adipose tissue; pink arrow = connective tissue; red arrows = malignant tissue). 1 cm scale bars are shown in the first column. In the optical images, surgical ink (yellow, orange, red) is visible along some specimen margins. Linear attenuation coefficient values correspond to 50 kVp. DWL = diffuse white light.

Figure 2.

Wide field-of-view images of representative invasive lobular carcinoma specimens (yellow arrows = adipose tissue; pink arrows = connective tissue; red arrows = malignant tissue). 1 cm scale bars are shown in the first column. In the optical images, surgical ink (orange, red, blue) is visible along some specimen margins. Linear attenuation coefficient values correspond to 50 kVp. DWL = diffuse white light.

Figure 3.

(A)–(D) Image similarity metrics quantified between micro-CT and either diffuse white light luminance or optical scatter images. (E) and (F) The coefficient of variation quantified for each image type. The legend in (A) applies to all subplots in (A)–(D). The legend in (E) also applies to (F). DWL Lum. = white light diffuse luminance; scatter = 490 nm optical scatter; CT = micro-CT; Ca = carcinoma; other = metaplastic tumor.

Figure 4.

Representative tumor slices demonstrating intra-tumoral fibrous structures. Regions of interest (white squares, 1.5 cm × 1.5 cm, column 1) magnify the malignant primary tumor (red lines) in the following four columns. Ring artifacts are seen in the micro-CT images in the top two rows, and a microcalcification is seen in the micro-CT of the last specimen (yellow arrow). 1 cm scale bars are shown for each row. Linear attenuation coefficient values correspond to 50 kVp.DWL = diffuse white light; IDCa, IG = invasive ductal carcinoma, intermediate grade; ILCa = invasive lobular carcinoma.

Figure 5.

Representative tumor slices exhibiting malignant tissue boundaries (red lines/arrows) with adjacent non-malignant fibrous tissue (pink lines/arrows = healthy connective tissue; cyan line/arrow = fibrocystic disease). Regions of interest (white squares, 2 cm × 2 cm, column 1) magnify malignant tissue boundaries in the following four columns. A beam hardening artifact from a surgical clip is seen in the top row micro-CT (yellow arrow), and a ring artifact is present in the bottom micro-CT. 1 cm scale bars are shown for each row. Linear attenuation coefficient values correspond to 50 kVp. DWL = diffuse white light; Ca = carcinoma; IDCa, LG = invasive ductal carcinoma, low grade; IDCa, IG = invasive ductal carcinoma, intermediate grade; IDCa, IG = invasive ductal carcinoma, high grade.

Figure 6.

(A) Intra-tumoral structure CV values from 1.5 cm × 1.5 cm tumor-bearing ROIs shown in figure 4. (B) Tumor boundary CV values from 2.0 cm × 2.0 cm ROIs shown in figure 5. (C) TBCR values quantified in 2 mm diameter samples on either side of the tissue boundary (solid colored dots in figure 5 column 1).DWL Lum. = diffuse white light luminance; scatter = 490 nm optical scatter; Ca = carcinoma; IDCa, LG = invasive ductal carcinoma, low grade; IDCa, IG = invasive ductal carcinoma, intermediate grade; IDCa, IG = invasive ductal carcinoma, high grade; ILCa = invasive lobular carcinoma.