## 4 Discussion  
In this study, a hybrid DOI method is presented that combines discrete wavelength FD and broadband CW reflectance measurements for quantitative measurements of the optical properties of deep tissue inclusions with a simple reflectance-based handheld probe configuration. Simulations showed that the new hybrid DOI method demonstrates enhanced accuracy with a relatively low mean percentage difference from true values in \(\mu_{a}\) reconstructions over the conventional topographic DOI technique for both normal and tumor-containing tissue at all tumor depths considered. This showed that partial volume artifacts, unlike the homogeneous model reconstructions employed by the conventional method, were corrected by the hybrid DOI method. The hybrid DOI technique also demonstrated accuracy and repeatability in recovering hyperspectral absorption on the two heterogeneous phantoms A and B at varying inclusion depths in Figure 11.  
The hybrid DOI results for deep inhomogeneities (such as 10 mm) show large error bars at wavelengths above 900 nm compared to the conventional topographic DOI results (Figures 9 and 10). This is because in topographic DOI, a homogeneous model is employed where all photons measured at the tissue surface are considered to estimate optical properties for the homogeneous medium. However, in the hybrid technique, optical properties are estimated for tumor and normal regions separately. To estimate the optical properties of the inhomogeneity, the hybrid technique requires photons measured at the surface that have traversed the optical inhomogeneity/tumor (>10 mm). Therefore, for deeper inclusions (such as 10 mm), the light measured that have traversed the inhomogeneity/inclusion is limited, thereby resulting in more variation over repetitions. However, the simulations and the phantom experimental results show that the hybrid DOI technique demonstrates at poor scattering recovery for deeper inhomogeneities. The hybrid DOI technique recovered broadband \(\mu_{\text{s}}\)' with a mean percent difference of \(\sim\)48% and \(\sim\)52% over all wavelengths for the 10 mm tumor depth simulation and the deep end of Phantom B (predicted inclusion depth 9 mm), respectively. As expected, accuracy is reduced when attempting to characterize deeper inhomogeneities. Indeed, the poor scattering recovery of the deep lesions compared to the conventional topographic technique was unexpected. We have investigated the amplitude and phase sensitivity with respect to absorption and scattering for increasing tumor depths from 0 to 10 mm, and'it was observed that the overall sensitivity of amplitude and phase to scattering is considerably lower compared to the sensitivity to absorption. In addition, the sensitivity of amplitude to scattering was observed to decreases drastically when the tumor depth increases from 5 mm to 10 mm. Therefore, we can conclude that the scattering differences are not as perceptible as the absorption in deeper inclusions. However, FD component can still be considered significant in deeper, as it estimates a good scattering for the background/normal tissue. As part of our future work, we will perform more simulations to study this effect, but we hypothesize that this is due to reduced signal to noise ratio because of the increased optical attenuation in deeper tumors. Reflectance-based handheld probes have the advantage of being fast and portable, can be applied to a wide range of imaging applications, and used in a variety of clinical settings. We have investigated the ability to recover the broadband optical properties of a buried tumor-like inclusion using measurements captured with a single SDS probe translated in grid pattern. Besides representing a straightforward case for our analysis, this probe configuration was the same used in the ACRIN 6691 multicenter clinical trial of diffuse optical spectroscopy in breast cancer therapy.