Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy

Daekeun Kim; Ki Hean Kim; Siavash Yazdanfar; Peter T. C. So

doi:10.1117/12.597055

30 March 2005 Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy

Daekeun Kim, Ki Hean Kim, Siavash Yazdanfar, Peter T. C. So

Author Affiliations +

Proceedings Volume 5700, Multiphoton Microscopy in the Biomedical Sciences V; (2005) https://doi.org/10.1117/12.597055
Event: SPIE BiOS, 2005, San Jose, CA, United States

Abstract

Histological analysis is the clinical standard for assessing tissue health and the identification of pathological states. Its invasive nature dictates that its use should be minimized without compromising diagnostic accuracy. A promising method for minimally invasive histological analysis is optical biopsy, which provides cross sectional or 3D images without any physical sectionings. Optical biopsy method based on multiphoton excitation microscopy can image cross-sectional image for deep tissue structures with subcellular resolution based on tissue endogenous fluorescence molecules. Despite its suitability for tissue imaging, multiphoton microscopy has not been used for in vivo clinical applications due to both compactness and imaging speed problems. We are developing a high-speed, handheld, miniaturized multifocal multiphoton microscope (H²M⁴) as an optical biopsy probe to enable optical biopsy with subcellular resolution. We incorporate a compact raster scanning actuator based on optimizing a piezo-driven tip tilt mirror by increasing its bandwidth, and reducing its nonlinearity. For flexible light delivery, we choose a photonic bandgap crystal fiber, which transmits ultrashort pulsed laser delivery with reduced spectral distortion and pulse width broadening. We further demonstrate that this fiber produces minimal spatial mode distortion and can achieve comparable image point spread function (PSF) as free space delivery. We further investigate the applicability of multiphoton microscopy for clinical dermal investigation by imaging ex vivo human skins with both normal and abnormal physiologies. This demonstrates the performance of H²M⁴ and the possibility of optical biopsy for diagnosing skin diseases.

Citation Download Citation

Daekeun Kim, Ki Hean Kim, Siavash Yazdanfar, and Peter T. C. So "Optical biopsy in high-speed handheld miniaturized multifocal multiphoton microscopy", Proc. SPIE 5700, Multiphoton Microscopy in the Biomedical Sciences V, (30 March 2005); https://doi.org/10.1117/12.597055

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