Research Highlights
(In Press, Journal of Biomedical Optics)
The goal of our latest study was to identify the near-infrared (NIR) functional contrast between normal breast tissue and breast tissue with malignant tumors within a small but statistically relevant population of subjects.We define contrast as the difference between malignant and normal tissues. In this report we present the results from a clinical study of 58 stage II/III malignant breast tumors using the LAMMP-derived technology of SSFDPM.
Linescans of both normal and diseased tissues were taken by moving the SSFDPM handheld probe over the regions of interest.Tumor locations were known a priori via standard mammography and/or ultrasound.At each measured location, the complete NIR absorption and reduced scattering spectra were measured.The absorption spectra were translated into chromophore concentrations of the dominant NIR absorbers, oxy-hemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb), water (ctH2O), and lipids.The reduced scattering (μs′) spectra were fitted to a power law function of the form μs′ = Al-SP, where SP is termed the scatter power and A is termed the scatter amplitude.
Table 1 provides the results of comparisons between tumor and normal linescan tissue regions. We performed non-parametric standard tests for significance for these values (Wilcoxon Ranked-sum test). The results of the analysis show that the basis chromophores, HHb, O2Hb, H2O, and lipids, all display statistically significant differences between normal and malignant tumor-containing tissue.Significance was achieved at the 95% confidence interval using a 2-tailed distribution. As for calculated indices, the total hemoglobin concentration (ctTHb) displayed statistical significance while the tissue hemoglobin saturation (stO2) did not. All errors presented represent the standard deviation of the population average.
| PARAMETER | TUMOR | NORMAL | P | ||
| Name | Mean | Median | Mean | Median | Wilcoxon |
| ctHHb | 5.92±2.42 | 5.42 | 9.98±5.02 | 8.82 | <0.0001* |
| ctO2Hb | 14.6±7.5 | 12.6 | 21.5±11.3 | 18.9 | 0.0006* |
| LIPID | 63.2±12.3 | 64.7 | 49.7±18.0 | 53.4 | <0.0001* |
| ctH2O | 20.0±10.5 | 16.3 | 33.8±21.0 | 27.2 | <0.0001* |
| ctHHB | 0.634±0.278 | 0.530 | 0.830±0.412 | 0.708 | 0.0108* |
| stO2 | 67.7±8.82 | 68.9 | 65.6±11.7 | 67.4 | 0.47 |
| ctTHb | 20.6±9.5 | 18.4 | 31.4±15.2 | 26.6 | <0.0001* |
Changes in ctHHb were the most significant of all the base parameters. We found that ctHHb generally produced the largest relative changes in terms of both average (48%) and peak (68%) linescan values. Although ctHHb is the most sensitive parameter, additional tissue constituents such as water and lipid also produced significant differences that could aid in the detection and characterization of breast lesions.For the peak tumor values, we observed changes in absolute percent for lipids and water to be >13% for each parameter.
Surprisingly the stO2 was the least sensitive figure of merit presented here. In particular, the average value of the stO2 linescan was not significantly different than the normal linescan. The stO2 has been commonly used as a figure of merit for breast cancer detection. According to our results, the hemoglobin concentrations themselves were far better indices for cancer detection. Even the minimum stO2 value of the tumor linescans averaged for all subjects was about 61%.There were patients where the stO2 dropped significantly, as one might expect, but this was not always the case. Typically we have seen large stO2 decreases in large necrotic tumors.Also the hemoglobin concentration in breast is relatively low, especially in the post-menopausal breast, so that small errors in concentration manifest as large errors in stO2. This error will only be amplified by ignoring the contribution of water and lipids.
