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Optical Coherence Tomography (OCT) is a powerful label-free approach for volumetric morphological imaging with numerous applications, especially within biomedicine. The penetration depth of OCT reaches well beyond conventional microscopy; however, signal reduction with depth leads to a rapid degradation of the signal below the noise level. The important pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. This has been valid for many microscopies; however, here, we postulate that in OCT, multiple scattering can enhance image contrast at depth. We demonstrate this using an original geometry that completely decouples the incident and collection light fields by introducing a spatial offset between them. This approach leads to a preferential collection of multiply scattered light with depth, compensating for signal attenuation and enhancing the image contrast at depth. A wave optics model and unified theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by over 24 dB. Our approach reveals mesoscale features in images of ex vivo mouse bone. Considering most approaches to date have aimed to minimize multiple scattering, our results suggest that the problem of OCT imaging at depth should be distinguished from optical microscopy at depth. This facile and widely applicable geometry enables a power capacity to dynamically tune for contrast at depth.

Type 2 Diabetes Mellitus (T2DM) is increasing in prevalence and its complications are potentially fatal. Recent studies suggest that long-term complications of T2DM include alterations of the bone, evident by a high coexistence rate of diabetes mellitus with both osteoporosis and different fracture types. Current measurements of fracture risk are based on Bone Mineral Density (BMD) measured via Dual-energy X-ray Absorptiometry (DXA); however, this method does not measure bone quality and often underestimates fracture risk in T2DM. Optical Coherence Tomography (OCT) holds the promise of early detection of diabetic bone microarchitectural alteration and serves as a possible non-ionizing alternative to DXA. The aim of this study is to evaluate the viability of using OCT-derived attenuation coefficients as a method for differentiating between healthy and diabetic bones in a diagnostic process. A TALLYHO/JngJ mouse model of diabetes was used and compared to a healthy control SWR/J; the differences in bone structure and quality of the TALLYHO/JngJ model compared with SWR/J is well documented in the literature. OCT cross-sectional images of four ex-vivo mouse femurs, two healthy and two T2DM, were used to calculate attenuation coefficients. Coefficients were calculated for the anterior side and the posterior side of the femurs. The posterior side was used as a control for the anterior side of the same femur sample. The attenuation-based comparison between healthy and diabetic bones shows that it is possible to differentiate between healthy and diabetic bones (p = 0.002). No significant difference in attenuation between the anterior and posterior side (p = 0.543, T2DM and p =0.055, healthy) was found. These preliminary results indicate that OCT-derived attenuation coefficients have the potential to differentiate between healthy and diabetic bones in a mouse model of T2DM.

The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics-based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth.

Type 2 diabetes mellitus (T2DM) is increasing in prevalence and its complications are potentially fatal. Recent studies suggest that long-term complications of T2DM include alterations of the bone, evident by a high coexistence rate of diabetes mellitus with both osteoporosis and different fracture types. Current measurements of fracture risk are based on bone mineral density (BMD) measured via dual-energy X-ray absorptiometry (DXA); however, this method does not measure bone quality and often underestimates fracture risk in T2DM. Optical coherence tomography (OCT) holds the promise of early detection of diabetic bone microarchitectural alteration and serves as a possible non-ionizing alternative to DXA. The aim of this study is to evaluate the viability of using OCT-derived attenuation coefficients as a method for differentiating between healthy and diabetic bones in a diagnostic process. A TALLYHO/JngJ mouse model of diabetes was used and compared to a healthy control SWR/J; the differences in bone structure and quality of the TALLYHO/JngJ model compared with SWR/J is well documented in the literature. OCT cross-sectional images of four ex-vivo mouse femurs, two healthy and two T2DM, were used to calculate attenuation coefficients. Coefficients were calculated for the anterior side and the posterior side of the femurs. The posterior side was used as a control for the anterior side of the same femur sample. The attenuation-based comparison between healthy and diabetic bones shows that it is possible to differentiate between healthy and diabetic bones (p = 0.002). No significant difference in attenuation between the anterior and posterior side (p = 0.543, T2DM and p =0.055, healthy) was found. These preliminary results indicate that OCT-derived attenuation coefficients have the potential to differentiate between healthy and diabetic bones in a mouse model of T2DM.