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Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements

机译：紧凑型固态CMOS单光子探测器阵列，用于体内NIR荧光寿命肿瘤学测量

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In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores’ lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the avb3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG􀀀E[c(RGDfK)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG􀀀c(RGDfK). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions.
机译：在近红外荧光引导的手术肿瘤学中，将健康组织与癌性组织区分开来是一项挑战。一种有前途的研究途径是分析外源荧光团的寿命，然而，其寿命在（亚）纳秒范围内。我们已经在一个紧凑的时间门控测量系统FluoCam中集成了基于标准CMOS SPAD（单光子雪崩二极管）的单光子像素阵列。体内测量是以吲哚花青绿（ICG）修饰的针对avb3整联蛋白的衍生物进行的，首先是在经基因工程改造的黑色素瘤小鼠模型上注射了结合了四聚环五肽的ICG（ICG＆＃x100000; E [c（RGDfK）4] ），然后在携带U87-MG（人原发性胶质母细胞瘤细胞系）肿瘤异种移植物的小鼠上注射ICG＆＃x100000; c（RGDfK）单体。对肿瘤，肌肉和尾巴位置的测量使我们能够证明使用FluoCam进行体内寿命测量的可行性，以确定特征寿命（约500 ps）以及结合的和未结合的ICG修饰的荧光团之间的细微差别（10％的水平） ，并估算实际条件下可用的光子通量。

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