# Time-Domain Near-Infrared Spectroscopy and Imaging: A Review
## 5 Studies toward Clinical Applications of TD-NIRS
### Time-Domain Diffuse Optical Tomography (TD-DOT)
#### 5.3.5 Breast Imaging  
Breasts are recognized to have smaller \(\mu_{a}\) and \({\mu_{s}}^{\prime}\) than other tissues so that transmittance measurements are available. [PERSON] et al. [188] developed a transmittance TD-DOT system to image the optical properties of breast phantoms and reported the potentiality of TD-DOT for breast tumor diagnosis. The same group used the TD system with an exogenous agent, indocyanine green (ICG), for image enhancement in in vivo measurements on patients [189]. They obtained better localization of target tumors, observed the differences in the ICG distributions among malignant tumors, benign tumors, and healthy tissues, and compared the DOT images with the concurrently acquired gadolinium-enhanced MRI images. However, the use of exogenous agents for frequent measurements may cause complications for patients and may thus be avoided.  
[PERSON] et al. [190] reported a four-wavelength (760, 780, 830, and 850 nm) TD-DOT system for breast tumor measurement using a commercially available instrument. Tomographic images reconstructed by a non-linear inversion algorithm showed the distributions of \(C_{oxy-HB}\), \(C_{deoxy-HB}\), water content, and lipid content in compressed breasts from 49 patients, and differences in the blood content and water fraction between malignant and benign tumors were found.  
For the purposes of screening of breast cancers and of evaluating the effectiveness of chemotherapy for breast cancers, [PERSON] et al. [52] used a 48-channel TD-DOT system. In the DOT images of the breasts, cancer tissues were imaged with higher absorption than healthy surrounding tissues. In the case of breast cancers which had positively responded to chemotherapy, \(\mu_{a}\) of the tumor after chemotherapy drastically decreased by 34% from 0.0076 mm\({}^{-1}\) before chemotherapy, indicating the effectiveness of quantitative evaluation of chemotherapy. [PERSON] et al. [53] used a 12-channel TD-NIRS system with a hand-held probe for use at bed side and indicated the usefulness of the TD-DOT system for evaluation of the effectiveness of chemotherapy to breast cancers.  
[PERSON] et al. [191] investigated the response to hormone therapy of breast cancers using a 3D TD-DOT system. They found that the images of \(\Delta C_{total-HB}\) strongly correlated with the clinical assessment of response to hormone treatment of breast cancers.  
[PERSON] et al. [192] demonstrated the feasibility of improving the breast tumor diagnosis using combined TD-DOT and TD-FI. They used two wavelengths of 780 nm and 830 nm for the source and measured the TOF-distributions at 32 sites around cylindrical phantoms. The modified GPST was employed to reconstruct the images of (\(\mu_{a}\), \(\mu_{s}\)\({}^{\prime}\)) and (\(y_{f}\), \(\tau_{f}\)) where \(y_{f}\) and \(\tau_{f}\) are the fluorescence yield and lifetime, respectively. The images of (\(\mu_{a}\), \(\mu_{s}\)\({}^{\prime}\)) and (\(y_{f}\), \(\tau_{f}\)) were reconstructed independently with a reasonable quantitativelyness, but when the images of (\(y_{f}\), \(\tau_{f}\)) were used to provide the locations of targets as prior information for reconstructing (\(\mu_{a}\), \(\mu_{s}\)\({}^{\prime}\)) images (fluorescence guided DOT), the quantitativelyness of the (\(\mu_{a}\), \(\mu_{s}\)\({}^{\prime}\)) images was highly improved; for example, the ratios of the reconstructed to correct values of (\(\mu_{a}\), \(\mu_{s}{{}^{\prime}}\)) were (23.5%, 31.0%) for separate reconstruction and (76.6%, 86.2%) for fluorescence guided reconstruction.