Imaging Platform Based On Nonlinear Optical Microscopy For Rapid Scanning Large Areas Of Tissue
- 技术优势
- The present invention improves existing nonlinear optical microscopy instruments by allowing for a much larger field of vision (FOV) (at least 5 larger), while also improving the scan speed (at least 15 times faster), without compromising the sub-micron resolution, making it more suitable for clinical use (e.g., provide diagnoses).
- 技术应用
- The present invention is applicable to medical and healthcare industries, which rely on non-invasive skin imaging, for detection of skin diseases, like skin cancer. Additionally, the present invention is applicable to optical microscopy and micro-spectroscopy for biological and biophysical research.
- 详细技术说明
- Nonlinear optical microscopy (NLOM) is a widely adopted imaging technique in the life sciences and is emerging as a highly valuable tool in biomedical and clinical applications. NLO microscopy uses a set of noninvasive imaging techniques that provide high resolution three-dimensional (3D) label-free molecular contrast of endogenous components in a tissue sample. This technique uses a focused laser beam that is raster-scanned across the sample to create high-resolution images upon signal detection. A 3D view of the sample can be reconstructed by scanning at multiple depths. The ability to generate high resolution 3D maps of specific tissue molecular compounds (i.e., flavin adenosine dinucleotide (CAD), reduced nicotinamide adenine dinucleotide (NADH), collagen, keratin, melanin, elastin fibers, lipids, proteins and water) without the need for extrinsic labels makes it an ideal imaging technique for superficial tissues in vivo. In particular NLO microscopy is a preferred tool for label-free imaging of skin in vivo. In skin in vivo, high resolution imaging is combined with a label-free contrast mechanism. The contrast is mainly derived from second harmonic generation (SHG) of collagen and two-photon excited fluorescence (TPEF) of tissue components such as the co-factors NADH and FAD + , elastin, keratin, and melanin. Clinical examination of skin crucially relies on the ability to quickly examine large tissue areas and rapidly zoom in to regions of interest. Skin lesions often show irregularity in color and appearance, especially when they start to progress towards malignancy. Examination of the entire lesion is essential to avoid false negative diagnostic assessments. Therefore, imaging of large field of views (FOVs) and automatic translation of the inspected area are practical requirements for reliable clinical imaging. Commercial clinical microscopes based on multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) have implemented automatic translation of an imaging area. However the initial FOV is typically limited to less than 0.5x0.5 mm2 and thus, assessing large areas of several mm2 at different depths may be time consuming and impractical for clinical use. Similarly, while there have been advances in NLOM systems capable of appreciable FOVs (imaging up to 80 mm2 at a maximum speed of 5mm/ms), it has been at the expense of lateral resolution (between 1.2 μm and 2 μm across the entire FOV). The present invention improves existing NLO microscopy designs by allowing for faster imaging and a larger FOV of large volumes of biological tissues or other materials, ex vivo or in vivo, at sub-micron resolution. The present invention is designed specifically for clinical imaging of human skin, and features a large FOV of 800x800 μm2 acquired at a maximum frame rate of 10 frames/s, while maintaining submicron spatial resolution. A field of view of 1.2x1.2 mm2 can be obtained at the expense of increased field curvature. The design of the scan head includes a fast galvanometric scanner, relay optics, a beam expander and a high NA objective lens. The system is optimized based on the Olympus 25x, 1.05NA water immersion lens that features a long working distance of 2 mm. This objective has a focal distance of 7.2 mm (based on a tube lens focal length of 180 mm) and an entrance pupil diameter of approximately 15 mm. Proper tailoring of the beam expander, which consists of the scan and tube lens elements, enables scaling of the FOV. The beam expander of our system has a 1.8x magnification, determined by the maximum beam diameter of 9 mm allowed by the scanning mirror and the objective entrance pupil diameter, 15 mm. Lastly, the design criteria include a flat wavefront of the beam, minimum field curvature, and suppressed spherical aberrations. All aberrations in focus are below the Marechal criterion of 0.07λ rms for diffraction-limited performance.
- *Abstract
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The present invention discloses a nonlinear optical microscopy (NLOM) instrument for rapid imaging of wide areas and large volumes of biological tissues or other materials, ex vivo or in vivo, at sub-micron resolution. The instrument allows much larger field of view (FOV) at the same time improves the scan speed.
- *IP Issue Date
- Apr 26, 2018
- *Principal Investigation
-
Name: Mihaela Balu
Department:
Name: Hideharu Mikami
Department:
Name: Eric Potma
Department:
Name: Bruce Tromberg
Department:
- 其他
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State Of Development
The laser-scanning microscope is in working prototype stage. Optimization of the imaging platform for clinical use is in progress.
Related Materials
Tech ID/UC Case
27435/2016-756-0
Related Cases
2016-756-0
- 国家/地区
- 美国
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