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/cm2) are more likely to be permanent. There exists a turning point of fluence rate (314 mW/cm2), 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.
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