Radiation therapy (RT) is widely used for cancer treatment, alone or in combination with other therapies. Recent RT advances have revived interest in delivering higher dose in fewer fractions, which may invoke both cellular and microvascular damage mechanisms. Microvasculature may thus be a potentially sensitive functional biomarker of RT early response, especially for such emerging RT treatments. However it is difficult to measure directly and non-invasively, and its time course, dose dependencies, and overall importance in tumor control are unclear. We use functional optical coherence tomography for quantitative longitudinalin vivoimaging in preclinical models of human tumor xenografts subjected to 10, 20 and 30 Gy doses, furnishing a detailed assessment of vascular remodeling following RT. Immediate (minutes to tens of minutes) and early (days to weeks) RT responses of microvascular supply, as well as tumor volume and fluorescence intensity, were quantified and demonstrated robust and complex temporal dose-dependent behaviors. The findings were compared to theoretical models proposed in the literature.

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect (p < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma.

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. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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.

In this study, the electro-kinetic phenomena (EKP) induced in biological tissue by external electric field, while not directly visible in optical coherence tomography (OCT) images, were detected by analyzing their textural speckle features. During application of a low-frequency electric field to the tissue, speckle patterns changed their brightness and shape depending on the local tissue EKP. Since intensities of OCT image speckle patterns were analyzed and discussed in our previous publications, this work is mainly focused on OCT signal phase analysis. The algorithm for extracting local spatial phase variations from unwrapped phases is introduced. The detection of electrically induced optical changes manifest in OCT phase images shows promise for monitoring the fixed charge density changes within tissues through their electro-kinetic responses. This approach may help in the identification and characterization of morphology and function of healthy and pathologic tissues.