Coherent raman tissue spectroscopy for in vivo disease diagnosis

早期诊断，及时治疗，癌症患者的存活率更高。因此，在过去的10-15年里，在不同的临床应用中，光学诊断已经有了很大的努力，包括基于组织的光吸收、弹性散射、荧光(内源性和外源性给药荧光团)的技术。根据信号强度、速度、分辨率(空间、时间和/或光谱)以及对改变的组织属性(结构、生化、分子)的敏感性和特异性等因素，每种技术都有自己的优点和局限性。近红外拉曼光谱(NIRS)具有对组织生化变化敏感的独特优势，不需要添加造影剂或药物。它基于光被分子非弹性散射的现象，并探测(生物)分子的振动状态。近10年来，近红外光谱在非或微创组织的临床诊断(光学活检)方面得到了广泛的研究，对癌症的诊断和手术指导非常有帮助，但由于其信号强度低，在广泛的临床应用中遇到了重要的障碍。相干拉曼效应(CARS)可以用来产生比近红外光谱强得多的拉曼信号，而不存在与内源荧光有关的问题。这项建议的基本假设是，这种新的光学技术将提供对自发拉曼的必要改进，使其能够用于临床上的非侵入性癌症诊断的粗略和/或精细成像(更高的采样或生化图谱)。为了证明这一假设，我们将构建一个宽带CARS光谱系统，并在组织样本和癌症动物模型中将其性能与近红外光谱进行比较。一旦证明了CARS光谱相对于自发拉曼光谱的优越性，我们将在具有有限成像能力的原型的临床前试验中确认CARS光谱在体内的技术可行性。

The survival rate of cancer patients is better when a diagnosis is made early and treatment is carried out promptly. Hence, there has been a large effort in the development of optical diagnostics for different clinical applications over the last 10-15 years, including techniques based on light absorption by tissues, elastic scattering, fluorescence (endogenous and with exogenous administered fluorophores). Each of these techniques has its own strengths and limitations, depending on factors such as the strength of the signals, speed, resolution (spatial, temporal and/or spectral) and sensitivity and specificity to altered tissue properties (structural, biochemical, molecular). Near Infrared Raman Spectroscopy (NIRS) has the specific advantage that it is sensitive to changes in the tissue biochemistry, without additional contrast agents or drugs. It is based on the phenomenon of inelastic scattering of light by molecules and probes the vibrational states of (bio)molecules. NIRS has been investigated intensely especially in the past 10 years, for non- or minimally-invasive tissue clinical diagnostics ("optical biopsies"), and has been very helpful cancer diagnosis and surgery guidance, but has encountered important roadblocks for widespread clinical applications mainly related to its low signal strength. The coherent Raman effect (CARS) can be used to generate a Raman signal much stronger than in NIRS without problems related to endogenous fluorescence. The basic assumption in this proposal is that this novel optical technique will provide the necessary improvements over spontaneous Raman to permit its use for coarse and/or fine imaging (higher sampling or biochemical maps) in the clinic for non invasive cancer diagnosis. To prove this hypothesis, we will construct a broadband CARS spectroscopy system and compare its performance to NIRS in tissue samples and animal models of cancer. Once the superiority of CARS spectroscopy over spontaneous Raman has been demonstrated, we will confirm the technical feasibility of CARS spectroscopy in vivo in a pre-clinical trial with a prototype having limited imaging capabilities.