## 2 Materials and Methods
### Dual-Energy Computed Tomography (DECT) Measurement  
All CT examinations were performed on a dual-source multidetector-row scanner (SOMATOM Definition FLASH system, Siemens Healthcare). All patients lay in the supine position with hands raised on the scanner table. After the acquisition of lateral and anteroposterior topograms, each patient was scanned in the craniocaudal direction with their breath held after deep inspiration. Dual-energy images were acquired with an automatic exposure control system (Care dose 4D; Siemens Healthcare; Table 1).  
Image data with two different tube potentials (100 kVp and 140 kVp) were processed with dual-energy software (Syngovia version VB10B; Siemens Healthcare) running on a workstation. The Liver VNC application program (Siemens Healthcare) consists of a three-material decomposition algorithm analyzing soft tissue, fat, and iodine, and their relative changes of attenuation at different peak voltages [19]. This application normally uses the CT number of the liver as the CT number of soft tissue. In this study, the CT number of breast cancer was used instead of that of the liver, with this being determined in a previous study [25]. Assuming that every voxel in the field is composed of fat, soft tissue, and iodine, this spectral algorithm generates a map that encodes not only the iodine distribution, but also the fat distribution.  
In the first part of the study, a ROI was placed over the entire fibroglandular tissue, shown as an intermediate density region at the level of the nipple on a transverse image, to measure the fat fraction of fibroglandular tissue in normal breast by DECT (Figure 1b).  
To measure the fat content of breast cancer by DECT in the second part of the study, an image showing the largest diameter of the tumor was selected. In general, the measurement depth of the NIRS is stated as half of the source-detector separation distance. However, [PERSON] et al. reported that the influence of the chest wall was small, and that the tHB concentration was constant, when the skin-to-chest wall distance was 2 cm or more for the TD-DOS source-detector separation of 3 cm [26]. According to the relationship between the skin-to-chest wall distance and tHb, a semicircular ROI with a transverse diameter of 3 cm and a depth of 2 cm was placed over the tumor (Figure 1c). In the second part of the study, the fat fraction of normal breast was measured by placing the same ROI in a symmetrical area in the contralateral breast (Figure 1d). The remaining components of the fat-free fraction were calculated by subtracting the fat fraction from 100%. [PERSON] et al. measured twenty pairs of postmortem breast samples using chemical analysis as a gold standard [22]. They reported that the breast consisted mainly of water, lipid, and protein, whose measured values were about 10-70%, 25-90%, and 0-10%, respectively. In this study, the fat-free fraction of the breast is considered to be a parameter related to water content, as the breast is low in protein.  
Figure 1: ROIs on MRI and DECT. (**a**) ROI on an MRI image of fibroglandular tissue in a normal breast in the first part of the study. (**b**) ROI on a DECT image of fibroglandular tissue in a normal breast in the first part of the study. (**c**) ROI on a DECT image of breast cancer in the second part of the study. (**d**) ROI on a DECT image in a symmetrical area of the contralateral breast in the second part of the study. Yellow dashed lines show the measurement axes for TD-DOS. Blue arrows indicate the position of the source (S) and detector (D) fiber bundles.