Combining coherent imaging and nonlinear microscopy for early-stage cancer detection

Optical imaging is an attractive tool for medical diagnostics, as it is capable of imaging structures inside living tissue at much higher resolution than e.g. ultrasound or magnetic resonance imaging. Due to this high resolution, optical techniques enable the detection of small, disease-related changes in tissue morphology. The present gold standard for diagnosing cancer development is through histopathology, which requires painful and invasive biopsies to be taken at sometimes random locations, and has a significant risk of missing small early-stage tumors. Optical imaging enables fast and noninvasive tissue screening, achieving high resolution and contrast without the need for biopsies.To image at sub-cellular resolution, we have constructed a holographic microscope that employs light with an ultrabroadband spectrum, generated in a photonic crystal fiber. We exploit the short coherence length of this light source to produce holograms from a thin section inside tissue, allowing us to selectively look at cell structure at a specific depth. In addition, we are investigating two-photon microscopy to image cell structure inside living tissue, using sensitive detection of autofluorescence and second harmonic generation. Selective imaging of a slice of tissue in the epithelium (~10-100 mum deep) is of specific interest in cancer detection, as tumor formation usually starts in this layer before spreading into other parts of the body. We will present our results on combining single-shot 2D-OCT and microscopy to visualize developing tumors in cultured tissue samples, and discuss the prospects of our research for clinical applications.