Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction

Abstract

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 tomography with color Doppler US.

Materials and methods: The study was approved by the local internal review board committee and by the Human Subjects Research Review Board of Army Medical Research and Materiel Command. Signed informed consent was obtained, and the study was HIPAA compliant. Between May 2003 and March 2004, 65 consecutive women (mean age, 51 years; age range, 24-80 years) with 81 breast lesions underwent US-guided biopsy and were scanned with a combined imager. The hand-held probe, which consisted of a centrally located US transducer surrounded by near-infrared sensors, was used to simultaneously acquire coregistered US images and optical data. The lesion location obtained at US was used to guide optical imaging reconstruction. Light absorption was measured at two wavelengths. From these measurements, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration. A Student t distribution was used to calculate the statistical significance of mean maximum and mean average hemoglobin concentrations obtained in malignant and benign lesion groups, and P < .001 was considered to indicate a statistically significant difference.

Results: Biopsy results revealed eight early stage invasive carcinomas (malignant group) and 73 benign lesions (benign group). The mean maximum and mean average hemoglobin concentrations in the malignant group were 122 micromol/L +/- 26.8 (+/- standard deviation) and 88 micromol/L +/- 24.5, respectively. The mean maximum and mean average hemoglobin concentrations in the benign group were 55 micromol/L +/- 24.8 and 38 micromol/L +/- 17.4, respectively. Both the maximum and average total hemoglobin concentrations were significantly higher in the malignant group compared with the benign group (P < .001). When a maximum hemoglobin concentration of 95 micromol/L was used as the threshold value, the sensitivity, specificity, positive predictive value, and negative predictive value of optical tomography were 100%, 96%, 73%, and 100%, respectively, and the sensitivity, specificity, positive predictive value, and negative predictive value of color Doppler US were 63%, 69%, 19%, and 94%, respectively.

Conclusion: Findings indicate that optical tomography with US localization is feasible for differentiating benign and early stage malignant breast lesions.

Figure 1

Picture of combined probe and frequency domain near-infrared imager (arrow). Commercial US probe is located at center of combined probe, and optical source and detector fibers are distributed at periphery of probe. Because diffused photons launched from a source and received by a detector travel in a curved path, lesions underneath US probe can be imaged with high sensitivity.

Figure 2

Bar graph demonstrates average maximum total hemoglobin concentration obtained in seven groups. Group 1 represents carcinoma (121.6 μmol/L ± 26.8); group 2, fibroadenoma (65.9 μmol/L ± 25.5); group 3, fibrocystic changes (55.6 μmol/L ± 16.6); group 4, fibrosis (66.2 μmol/L ± 31.2); group 5, other solid benign lesions (55.2 μmol/L ± 25.2); group 6, complex cysts (40.7 μmol/L ± 21.3); and group 7, hyperplasia (56.2 μmol/L ± 0.0). Horizontal axis represents group number, and vertical axis represents maximum total hemoglobin concentration in micromoles per liter. Error bars indicate standard deviations.

Figure 3

Scatter plot shows maximum total hemoglobin concentration for carcinoma (small ▪), fibroadenoma (♦), fibrocystic changes (▴), fibrosis (•), other solid benign lesions (short bar), complex cysts (long bar), and hyperplasia (large▪). Total hemoglobin concentration is measured on vertical axis in micromoles per liter.

Figure 4

US image, optical absorption maps, and hemoglobin concentration maps of suspicious lesion at 3 o’clock position in left breast of 45-year-old woman. (a) US image demonstrates ill-defined, slightly heterogeneous, and mildly hypoechoic mass (arrow) measuring 6 mm in diameter. Color Doppler US revealed large blood vessels both inside and at periphery of lesion. Pathologic analysis revealed intraductal and invasive mammary duct carcinoma (nuclear grade 3, histologic grade 3). (b, c) Reconstructed optical absorption maps obtained at (b) 780 nm and (c) 830 nm. Optical absorption values range from 0 to 0.3 cm⁻¹. The first section (Slice #1 in b and c) is a 9 × 9-cm spatial x–y image obtained at a depth of 0.5 cm, as measured from skin surface, and the last section (Slice #7 in b and c) is a spatial x–y image obtained 3.5 cm toward chest wall. Spacing between sections is 0.5 cm in propagation direction. Lesion was well resolved in section two (Slice #2). (d) Total hemoglobin concentration map computed from absorption maps of b and c. Hemoglobin map revealed an isolated high concentration mass in section two (Slice #2). Maximum hemoglobin concentration was 149.9 μmol/L, and average hemoglobin concentration was 121.1 μmol/L, as calculated within FWHM region. Average total hemoglobin concentration of background areas outside FWHM region was 29.0 μmol/L. Vertical scale presents total hemoglobin concentration in micromoles and ranges from 0 to 150 μmol/L.

Figure 5

US image and hemoglobin concentration maps of infiltrating lobular carcinoma (nuclear grade 2–3) located at 12 o’clock position in right breast of 37-year-old woman. (a) US image demonstrates lesion (arrow) measuring 1 cm in diameter. No blood vessels or blood flow were seen at color Doppler US. (b) Total hemoglobin concentration map computed from absorption maps (not shown) obtained at 780 nm and 830 nm. Hemoglobin map reveals isolated high concentration mass in sections three (slice #3) and four (slice #4). Maximum hemoglobin concentration was 102.1 μmol/L, and average hemoglobin concentration was 68.7 μmol/L, as measured within FWHM region. Vertical scale presents total hemoglobin concentration in micromoles and ranges from 0 to 150 μmol/L.

Figure 6

US image and hemoglobin concentration maps of suspicious 6-mm lesion located at 7 o’clock position in right breast of same patient as Figure 5. (a) US image demonstrates lesion (arrow). No blood vessels or blood flow were seen at color Doppler US. Biopsy result revealed benign nonproliferative fibroadipose breast tissue. (b) Total hemoglobin concentration map computed from absorption maps (not shown) obtained at 780 nm and 830 nm. No resolvable lesion was found in hemoglobin map, and maximum total hemoglobin concentration was only 24.2 μmol/L. Vertical scale represents total hemoglobin concentration in micromoles and ranges from 0 to 150 μmol/L.

Figure 7

US image and hemoglobin concentration maps of suspicious 1.9 × 1.1-cm lesion at 9 o’clock position in right breast of a 75-year-old woman. (a) US image demonstrates lesion with solid component adjacent to cyst (arrow). Large blood vessels were seen at periphery of lesion during color Doppler US. Biopsy result revealed intraductal papilloma, with no evidence of atypical cells or malignancy. (b) Total hemoglobin concentration map computed from absorption maps (not shown) obtained at 780 nm and 830 nm. Vertical scale presents total hemoglobin concentration in micromoles and ranges from 0 to 150 μmol/L. Maximum total hemoglobin concentration was 38.2 μmol/L, and average total hemoglobin concentration was 26.3 μmol/L, as measured within FWHM region. Total hemoglobin distribution was diffused rather than localized, as seen in cases of malignancy.

Figure 8

US image and hemoglobin concentration maps of 1.3 × 1.0-cm lesion, simple cyst, and complex cyst located between 3 o’clock and 4 o’clock positions in left breast of 59-year-old woman. (a) US image demonstrates simple cyst with adjacent complex cyst or solid nodule (arrow). Complex cyst was aspirated completely, and no residual abnormality was noted. (b) Total hemoglobin concentration map indicates low hemoglobin concentration at central location of cyst (arrow) close to origin in section 2 (slice #2). Light absorption maps (not shown) indicated low light absorption. Incomplete ring with higher light absorption and high hemoglobin concentration was observed surrounding cyst. Although measured total hemoglobin concentration was highest in complex cyst owing to higher absorption ring, distribution was obviously different from malignant cases (maximum total hemoglobin concentration, 94 μmol/L; average total hemoglobin concentration, 62.8 μmol/L, as measured within FWHM region). Cysts, in general, have low light absorption (and therefore low hemoglobin concentration) owing to low water absorption in wavelength range studied. The higher absorption ring was likely caused by the cyst wall. This example suggests that both hemoglobin distribution and threshold level must be evaluated for accurate diagnosis of suspicious lesions.