Longitudinal in-vivo quantification of tumour microvascular heterogeneity by optical coherence angiography in pre-clinical radiation therapy.

Stereotactic body radiotherapy (SBRT) is an emerging cancer treatment due to its logistical and potential therapeutic benefits as compared to conventional radiotherapy. However, its mechanism of action is yet to be fully understood, likely involving the ablation of tumour microvasculature by higher doses per fraction used in SBRT. In this study, we hypothesized that longitudinal imaging and quantification of the vascular architecture may elucidate the relationship between the microvasculature and tumour response kinetics. Pancreatic human tumour xenografts were thus irradiated with single doses of [Formula: see text], [Formula: see text] and [Formula: see text] Gy to simulate the first fraction of a SBRT protocol. Tumour microvascular changes were monitored with optical coherence angiography for up to [Formula: see text] weeks following irradiation. The temporal kinetics of two microvascular architectural metrics were studied as a function of time and dose: the diffusion-limited fraction, representing poorly vascularized tissue [Formula: see text] µm from the nearest detected vessel, and the vascular distribution convexity index, a measure of vessel aggregation at short distances. These biological metrics allowed for dose dependent temporal evaluation of tissue (re)vascularization and vessel aggregation after radiotherapy, showing promise for determining the SBRT dose-response relationship.

Volumetric tumor delineation and assessment of its early response to radiotherapy with optical coherence tomography.

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.

Optical assessment of tissue anisotropy in ex vivo distended rat bladders.

Microstructural remodelling in epithelial layers of various hollow organs, including changes in tissue anisotropy, are known to occur under mechanical distension and during disease processes. In this paper, we analyze how bladder distension alters wall anisotropy using polarized light imaging (followed by Mueller matrix decomposition). Optical retardance values of different regions of normal rat bladders under different distension pressures are derived. Then optical coherence tomography is used to measure local bladder wall thicknesses, enabling the calculation of the tissue birefringence maps as a measure of the tissue anisotropy. Selected two-photon microscopy is also performed to better understand the compositional origins of the obtained anisotropy results. The dome region of the bladder shows maximum birefringence when the bladder is distended to high pressures, whereas the ventral remains roughly isotropic during distension. In addition, the average anisotropy direction is longitudinal, along the urethra to dome. The derived wall anisotropy trends are based on birefringence as an intrinsic property of the tissue organization independent of its thickness, to aid in understanding the structure-functions relation in healthy bladders. These new insights into the wall microstructure of ex vivo distending bladders may help improve the functionality of the artificially engineered bladder tissues.