## 4 Discussion
We confirmed our hypothesis that applying the hybrid DOI technique could greatly improve the accuracy of tumor characterization compared to the homogeneous topographic approach used in ACRIN 6691 and related studies [36]. This would be helpful, for example, in better resolving optical property differences in highly attenuating tissue regions such as characterizing breast masses in the area. Therefore, in this study, our goal was to compare the accuracy of the hybrid DOI technique to the traditional topographic approach when applied to the same raw diffuse optical dataset. Topographic DOI does not consider any depth-dependent variations in the tissue composition and assumes optical homogeneity, which contributes to significant errors in optical property estimation of tissue inhomogeneities. On the contrary, the hybrid technique considers tissue inhomogeneities by reconstructing optical properties for different regions (normal and tumor) within the tissue. This additional spatial information is intended to be provided by complementary medical imaging, such as a ultrasound which has been integrated with reflectance-based DOI probes [40; 41]. Indeed, these studies have described how spatial guided techniques, such as ultrasound-guided DOI, help improve lesion localization and light quantification accuracy, which leads to more accurate estimation of hemoglobin content in breast lesions. Our method differs from these by providing access to much more optical contrast and chromophore accuracy through broadband optical property reconstruction. Though this study is not able to assess the clinical utility of this additional contrast and accuracy, we hypothesize that it would be beneficial in applications where accurate quantitative assessment of tissue optical properties is critical, such as in noninvasive diagnosis of human malignancies including breast, colorectal, and thyroid tumors. Furthermore, our technique is sensitive to absorption contributions from a priori unknown chromophores, which has been shown to be useful for different diagnosis of breast lesions [9; 10; 11; 12; 13]. Prior studies have also reported the measurement of broadband optical absorption over as many as 120 wavelengths using CW-only DOT measurements [42]. However, these studies assume that the tissue scattering coefficient is known, because the CW method alone has limited capability to separate absorption from scattering in the DOT reconstruction [25; 43]. This emphasizes the significance of the FD component in the hybrid DOI technique as it allows us to obtain good estimates of scattering across the entire wavelength range. The simulation and experimental results demonstrates that adding the FD component provides accurate absorption estimation for normal tissue and relatively shallow tumors. In addition, for deeper inhomogeneities (9 and 10 mm), a good scattering estimate of the normal tissue is significant to acquire accurate absorption estimates of the tumor. In this hybrid DOI approach, broadband optical properties are recovered at each wavelength individually without a priori spectral constrains, but with spatial constraints to reduce computational complexity and time. Use of prior information for reconstructions can be categorized as hard priors and soft priors [31]. Soft prior information has been extensively used in a number of experimental and clinical settings and has been found to be more robust in the presence of uncertainty in prior information [44; 45]. A limitation of our approach is requiring hard priors for the reconstructions wherein bulk homogeneous values are reconstructed for each region specified. We have restricted the hard prior reconstructions to two regions, namely, normal and tumor containing tissue. However, the same technique can also be extended to multiple regions, such as in cases of multiple lesions or to model heterogeneity within the tumor itself.