Sensitive assays for rapid quantitative analysis of histologic sections, resected tissue specimens, or in situ tissue are highly desired for early disease diagnosis. Stained histopathology is the gold standard but remains a subjective practice on processed tissue taking from hours to days. We describe a microscopy technique that obtains a sensitive and accurate color-coded image from intrinsic molecular markers. Spectrally reconstructed nonlinear interferometric vibrational imaging can differentiate cancer versus normal tissue sections with greater than 99% confidence interval in a preclinical rat breast cancer model and define cancer boundaries to ±100 μm with greater than 99% confidence interval, using fresh unstained tissue sections imaged in less than 5 minutes. By optimizing optical sources and beam delivery, this technique can potentially enable real-time point-of-care optical molecular imaging and diagnosis. Cancer Res; 70(23); 1–8. ©2010 AACR.

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