Analysis of semi-transparent low scattering biological structures in optical coherence tomography (OCT) has been actively pursued in the context of lymphatic imaging, with most approaches relying on the relative absence of signal as a means of detection. Here we present an alternate methodology based on spatial speckle statistics, utilizing the similarity of a distribution of given voxel intensities to the power distribution function of pure noise, to visualize the low-scattering biological structures of interest. In a human tumor xenograft murine model, we show that these correspond to lymphatic vessels and nerves; extensive histopathologic validation studies are reported to unequivocally establish this correspondence. The emerging possibility of OCT lymphangiography and neurography is novel and potentially impactful (especially the latter), although further methodology refinement is needed to distinguish between the visualized lymphatics and nerves.
We studied the protective effect of antioxidant echinochrome A on bleomycin-induced pulmonary fibrosis in rats at the early stages of postnatal ontogeny. Administration of echinochrome A was shown to reduce the severity of bleomycin-induced oxidative stress in the lungs, prevented the development of hypertrophy of interalveolar connective tissue and peribronchial lymphoid infiltration, and normalized the ratio of volume densities of interalveolar septa and alveolar lumen.
Texture analyses of optical coherence tomography (OCT) images have shown initial promise for differentiation of normal and tumor tissues. This work develops a fully automatic volumetric tumor delineation technique employing quantitative OCT image speckle analysis based on Gamma distribution fits. We test its performance in-vivo using immunodeficient mice with dorsal skin window chambers and subcutaneously grown tumor models. Tumor boundaries detection is confirmed using epi-fluorescence microscopy, combined photoacoustic-ultrasound imaging, and histology. Pilot animal study of tumor response to radiotherapy demonstrates high accuracy, objective nature, novelty of the proposed method in the volumetric separation of tumor and normal tissues, and the sensitivity of the fitting parameters to radiation-induced tissue changes. Overall, the developed methodology enables hitherto impossible longitudinal studies for detecting subtle tissue alterations stemming from therapeutic insult.
Radiation therapy (RT) is widely and effectively used for cancer treatment but can also cause deleterious side effects, such as a late-toxicity complication called radiation-induced fibrosis (RIF). Accurate diagnosis of RIF requires analysis of histological sections to assess extracellular matrix infiltration. This is invasive, prone to sampling limitations, and thus rarely used; instead, current practice relies on subjective clinical surrogates, including visual observation, palpation, and patient symptomatology questionnaires. This preclinical study demonstrates that functional optical coherence tomography (OCT) is a useful tool for objective noninvasive in-vivo assessment and quantification of fibrosis-associated microvascular changes in tissue. Data were collected from murine hind limbs 6 months after 40-Gy single-dose irradiation and compared with nonirradiated contralateral tissues of the same animals. OCT-derived vascular density and average vessel diameter metrics were compared to quantitative vascular analysis of stained histological slides. Results indicate that RIF manifests significant microvascular changes at this time point posttreatment. Abnormal microvascular changes visualized by OCT in this preclinical setting suggest the potential of this label-free high-resolution noninvasive functional imaging methodology for RIF diagnosis and assessment in the context of clinical RT.
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