COMPARISON OF OPTICAL POLARIMETRY AND DIFFUSION TENSOR MR IMAGING FOR ASSESSING MYOCARDIAL ANISOTROPY

We have recently proposed an optical method for assessing heart structure that uses polarized light measurement of birefringence as an indicator of tissue anisotropy.The highly aligned nature of healthy cardiac muscle tissue has a detectable effect on the polarization of light,resulting in a measurable phase shift(“retardance”).When this organized tissue structure is perturbed,for example after cardiac infarction(heart attack),scar tissue containing disorganized collagen is formed,causing a decrease in the measured retardance values.However,these are dependent not only on tissue anisotropy,but also on the angle between the tissue’s optical anisotropy direction and the beam interrogating the sample.To remove this experimental ambiguity,we present a method that interrogates the sample at two different incident beam angles,thus yielding enough information to uniquely determine the true magnitude and orientation of the tissue optical anisotropy.We use an infarcted porcine heart model to compare these polarimetryderived anisotropy metrics with those obtained with diffusion tensor magnetic resonance imaging(DT-MRI).The latter yields the anisotropy and the direction of tissue water diffusivity,providing an independent measure of tissue anisotropy.The optical and MR results are thus directly compared in a common ex vivo biological model of interest,yielding reasonable agreement but also highlighting some technique-specific differences.

Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8+ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.