Coherent raman tissue spectroscopy for in vivo disease diagnosis

早期诊断和及时治疗癌症患者的生存率更高。因此，在过去的10-15年中，在开发用于不同临床应用的光学诊断方面做出了很大的努力，包括基于组织的光吸收、弹性散射、荧光（内源性和外源性施用荧光团）的技术。这些技术中的每一种都有其自身的优势和局限性，这取决于诸如信号强度、速度、分辨率（空间、时间和/或光谱）以及对改变的组织性质（结构、生物化学、分子）的灵敏度和特异性等因素。近红外拉曼光谱（NIRS）具有对组织生物化学的变化敏感的特定优点，而无需额外的造影剂或药物。它基于分子对光的非弹性散射现象，并探测（生物）分子的振动状态。近红外光谱技术在过去的10年中得到了广泛的研究，用于非侵入性或微创组织临床诊断（“光学活检”），并且非常有助于癌症诊断和手术指导，但在广泛的临床应用中遇到了重要的障碍，主要与其低信号强度有关。相干拉曼效应（汽车）可用于产生比在NIRS中强得多的拉曼信号，而没有与内源荧光相关的问题。该建议的基本假设是，这种新的光学技术将提供对自发拉曼的必要改进，以允许其用于临床中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）。为了证明这一假设，我们将构建一个宽带汽车光谱系统，并在组织样本和癌症动物模型中将其性能与NIRS进行比较。一旦汽车光谱优于自发拉曼光谱的优势已经得到证明，我们将在临床前试验中使用具有有限成像能力的原型来确认汽车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.