Multimodal and multispectral microscopy for clinical diagnostics

目前对癌症等病理学的诊断依赖于通过活组织检查程序切除的组织样本的细胞评估。虽然这项技术允许对患病细胞进行评估，但活组织检查对患者来说是不舒服的，通常是危险的，样本处理非常耗时，而且只评估更大器官的有限部分，导致许多假阴性诊断。光学相干层析成像(OCT)和反射共焦显微镜(RCM)等光学成像技术是一种非侵入性光学技术，能够通过基于光纤的小型仪器在不同深度产生细胞的高分辨率图像。生物光子学研究的最新进展导致了新的更小、更灵敏的仪器，其成像速度允许对更大区域进行非侵入性调查，从而降低了与活组织检查相关的风险。在过去的十年中，这两种技术(RCM和OCT)都被证明在活体中产生了高质量的结构(OCT)、细胞和亚细胞(RCM)图像。然而，由于缺乏特定的造影剂来再现活检样本上使用的染色的效果，它们的临床应用仅限于少数几个无法进行活检的器官。拟议的研究计划的目标是利用线性和非线性光子与组织的相互作用，以符合成像内窥镜几何约束的方式增加临床显微镜图像的对比度和特异性。这种方法的独创性在于将生物学家传统使用的工具与新开发的光学诊断工具相结合，以产生具有高度特定对比度的高分辨率非侵入性内窥镜成像。该研究计划包括开发光子学工具，使其能够快速转移到临床，并导致开发下一代医学成像内窥镜，该内窥镜能够以细胞敏感性和分子特异性在体内对人体器官进行非侵入性成像。这些新的光学诊断技术将提供增强的诊断能力，允许在存活率和治愈机会最大的早期阶段检测疾病。

Current diagnoses of pathologies such as cancer rely on cellular evaluation of tissue samples excised through biopsy procedures. While this technique allows for evaluation of diseased cells, biopsies are uncomfortable for the patient, often hazardous, sample processing is time-consuming, and only a limited portion of a much larger organ is evaluated, resulting in a number of false-negative diagnoses. Optical imaging technologies such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are non-invasive optical technologies capable of producing high resolution images of cells at different depth through small, fibre-optics based instruments. The recent developments in biophotonics research have led to new smaller, more sensitive instruments having imaging speeds that allow non-invasive investigation of larger areas, reducing the risks associated with biopsies. Within the last decade, both these technologies (RCM and OCT) were shown to yield high quality structural (OCT), cellular and sub-cellular (RCM) images in vivo. However, the lack of specific contrast agents that would reproduce the effect of stains used on biopsy samples, limits their clinical utility to the few organs on which biopsies are impracticable. The objective of the proposed research program is to exploit linear and non-linear photon-tissue interactions to increase contrast and specificity of clinical microscopy images in ways that are compatible with constraints associated with the geometry of imaging endoscopes. The originality of this approach consists in combining tools traditionally used by biologists with newly developed optical diagnostics tools to yield high-resolution non-invasive endoscopic imaging with highly specific contrast. The research program includes the development of photonics tools that will enable the rapid transfer to the clinics, and lead to the development of the next generation of medical imaging endoscopes capable of non-invasively imaging human organs in vivo with cellular sensitivity and molecular specificity. These novel optical diagnostics technologies will provide enhanced diagnostics capability, allowing detection of diseases at earlier stages, where chances of survival and cure are the greatest.