## 4 Discussion
Furthermore, the TD-DOS method is less affected by the superficial layer, but more sensitive to deeper regions than other DOS methods [36; 37; 38]. In this study, the depth of ROI was determined as 2 cm based on the relationship between the skin-to-chest wall distance and the tHb [26]. In the case of breast measurement, the absorption in the 900 nm region, which reflects the characteristics of water and lipid, is fairly high compared with the absorption at 750-850 nm reflecting the characteristics of hemoglobin. It causes difficulty in detection of the photons which have passed through the deeper region in the 900 nm range. Therefore, it is expected that the water and lipid contents obtained by TD-DOS reflect the informationwithin the region shallower than 2 cm. In addition, the fat and fat-free fractions obtained by DECT change according to the size of ROI due to the heterogeneity of the breast tissue. For that reason, the regression slope in Figure 5 will be improved by employing a ROI that has more appropriate depth. Several reports have compared DOS-measured physiological parameters between normal and tumor breast tissue [4; 27; 39; 40; 41]. In tumor tissue, tHb and water are higher than those in normal tissue, while lipid is lower. A significant reduction in \(\text{StO}_{2}\) in tumor caused by tissue hypoxia due to metabolically active tumor cells has been reported [39; 41], but results showing no significant differences have also been reported [27]. High tHb reflects angiogenesis as a tumor grows, and [PERSON] et al. described the association between tHb level estimated by TD-DOS and mitotic count score evaluated as a proliferation marker, or \(\text{SUV}_{\text{max}}\) on FDG PET/CT [4]. High water content and low lipid content of tumors compared with normal tissue has also been reported using magnetic resonance spectroscopy (MRS) [42]. The high water content indicates edema and increased cellularity [43]. As breast tumors grow, adipose tissue is extruded, so a decrease in lipid content is predicted. Our results showed a significant difference in water and \(\text{StO}_{2}\) between tumor and normal tissue. Although tHb and lipid did not show a significant difference, tHb tended to be higher in the tumor (\(p\) = 0.063). In this study, differences in these parameters may not have been observed because the tumors were smaller in size than those in the previous report or because the number of cases was small. When all 32 patients, including ones only measured by TD-DOS (untreated patients, excluding one case with the probe resting on the nipple, and 2 cases with a hematoma near the tumor) were analyzed using the Wilcoxon signed rank test, and significant differences in the parameters became clear as the number of cases increased. We confirmed a significant decrease in lipid (\(p\) = 0.0043) and an increase in tHb (\(p\) = 0.0032) in tumor, as described in previous reports [27; 41]. The present study has some limitations. Since the number of patients was small, especially the number of patients with very low lipid content, the regression line between TD-DOS and DECT for lipid might be affected by this scarcity of lipid data. Furthermore, due to the small tumor size, some parameters (tHb and lipid) showed no significant difference between normal and tumor, unlike other cases reported in the literature. It has been reported that skin-to-chest wall distance, depth of the tumor, and thickness of the tumor, all affect the measurement values of breast cancer [26; 44]. [PERSON] et al. proposed tHbnet as an index of tHb for tumors in order to improve the evaluation of tumors by reducing the effect of the skin-to-chest wall distance, which differs among individuals. This measurement used a standard curve of tHb and skin-to-chest wall distance for a normal breast [44]. In addition, a tissue optical index (TOI) combining water, lipid, and HHb has also been proposed as a contrast function for cancer and normal tissue [27].