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In vivo near infrared (NIR) fluorescence imaging and laser speckle contrast imaging (LSCI) are emerging optical bioimaging modalities, which can provide information on blood vessels morphology, volume and the blood flow velocity. Optical tissue clearing (OTC) technique addresses a light scattering problem in optical bioimaging, which is imperative for the transcranial brain imaging. Herein, we report an approach combining NIR fluorescence and LSC microscopy imaging with OTC. A liposomal nanoformulation comprising NIR fluorescent dye ICG and photosensitizer BPD was synthesized and injected intravenously into mouse with OTC treated skull. Transcranial excitation of BPD in nanoliposomes resulted in the localized, irradiation dose dependent photodynamic damage of the brain blood vessels, which was manifested both in NIR fluorescence and LSC transcranial imaging, revealing changes in the vessels morphology, volume and the blood flow rate. The developed approach allows for bimodal imaging guided, localized vascular PDT of cancer and other diseases., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

The blood-brain barrier (BBB) is a dynamic barrier between the blood microcirculation system and the brain parenchyma, which plays an important role in the pathogenesis of a variety of neurological diseases. Meanwhile, a non-invasive therapeutic approach of photobiomodulation (PBM) has emerged as a promising treatment for neurological disorders through irradiation with near infrared (NIR) light. However, despite multiple encouraging results reported for PBM in vitro and in vivo , the mechanisms of its therapeutic effect on brain, especially on the BBB, remain barely known. Herein, the effect of NIR light irradiation on the in vitro BBB models was studied. 808 nm laser irradiation at the doses of 10 and 30 J/cm 2 was found to significantly increase the permeability of this BBB model. The results showed that NIR light affected mitochondria of cells in the in vitro BBB models, leading to an increase in the mitochondrial activity, reactive oxygen species (ROS) level and Ca 2+ influx. The activity of matrix metalloproteinases and the expression of the tight junction proteins in the endothelial cells were found to be inhibited by the NIR light, resulting in an increase in the BBB permeability. This study suggested a new strategy for drug transport across the BBB in development of treatments for brain disorders., Competing Interests: The authors declare no conflicts of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

This study investigates the fluence rate effect, an essential modulating mechanism of photodynamic therapy (PDT), by using photoacoustic imaging method. To the best of our knowledge, this is the first time that the fluence rate dependence is investigated at a microscopic scale, as opposed to previous studies that are based on tumor growth/necrosis or animal surviving rate. This micro-scale examination enables subtle biological responses, including the vascular damage and the self-healing response, to be studied. Our results reveal the correlations between fluence rate and PDT efficacy/self-healing magnitude, indicating that vascular injuries induced by high fluence rates are more likely to recover and by low fluence rates (≤126 mW/cm 2 ) are more likely to be permanent. There exists a turning point of fluence rate (314 mW/cm 2 ), above which PDT practically produces no permanent therapeutic effect and damaged vessels can fully recover. These findings have practical significance in clinical setting. For cancer-related diseases, the 'effective fluence rate' is useful to provoke permanent destruction of tumor vasculature. Likewise, the 'non effective range' can be applied when PDT is used in applications such as opening the blood brain barrier to avoid permanent brain damage., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)