Coherent raman tissue spectroscopy for in vivo disease diagnosis

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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.