Although the beneficial effects of regular physical exercise on brain aging and neurodegenerative diseases are well recognized, a clear understanding of how exercise leads to such benefits remains elusive. In this work, we investigated the effects of normal aging on cortical microvascular oxygenation, perfusion, and morphology and the impact of four months of voluntary wheel running on cortical microvascular oxygenation in 20 months old mice. We used two-photon microscopy to assess age-related and exercise-induced changes in the distributions of capillary oxygen partial pressure (PO2) and red-blood-cell flux across cortical depth in awake mice. Our finding suggests the mitigating effect of exercise on the progression of age-related changes in capillary oxygenation in deeper cortical layers which may be related to health-enhancing benefits of exercise in elderly individuals.
Although the development of tumor-targeted fluorescent probes is a major area of investigation, it will be several years before these probes are realized for clinical use. Here, we report an approach that employs indocyanine-green (ICG), a clinically approved, nontargeted dye, in conjunction with fluorescence lifetime (FLT) detection to provide high accuracy for tumor-tissue identification in mouse models of subcutaneous human breast and brain tmors. The improved performance relies on the distinct FLTs of ICG within tumors versus tissue autofluorescence and is further aided by the well-known enhanced permeability and retention of ICG in tumors and the clearance of ICG from normal tissue several hours after intravenous injection. We demonstrate that FLT detection can provide more than 98% sensitivity and specificity, and a 10-fold reduction in error rates compared to intensity-based detection. Our studies suggest the significant potential of FLT-contrast for accurate tumor-tissue identification using ICG and other targeted probes under development, both for intraoperative imaging and for ex-vivo margin assessment of surgical specimens.
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