Multifocal imaging systems and method

Abstract

In the systems and methods of the present invention a multifocal multiphoton imaging system has a signal to noise ratio (SNR) that is reduced by over an order of magnitude at imaging depth equal to twice the mean free path scattering length of the specimen. An MMM system based on an area detector such as a multianode photomultiplier tube (MAPMT) that is optimized for high-speed tissue imaging. The specimen is raster-scanned with an array of excitation light beams. The emission photons from the array of excitation foci are collected simultaneously by a MAPMT and the signals from each anode are detected using high sensitivity, low noise single photon counting circuits. An image is formed by the temporal encoding of the integrated signal with a raster scanning pattern. A deconvolution procedure taking account of the spatial distribution and the raster temporal encoding of collected photons can be used to improve decay coefficient. We demonstrate MAPMT-based MMM can provide significantly better contrast than CCD-based existing systems.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the priority of U.S. Provisional Application No. 60 / 684,608 filed May 25, 2005 entitled, MULTI FOCAL MULTIPHOTON IMAGING SYSTEMS AND METHODS, the whole of which is hereby incorporated by reference herein.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] N / A BACKGROUND OF THE INVENTION [0003] Systems and methods for microscopic analysis of biological material have been used for characterization and diagnosis in many applications. Fluorescence microscopy, for example, has been used for optical analysis including the histological analysis of excised tissue specimens. Optical coherence tomography has been used for three dimensional imaging of tissue structures, however, the limited resolution of existing systems has constrained its use for definitive pathological analysis. Confocal microscopy has been used for high resolution imaging and has controllable depth of field but limited imaging speed. ...

AI Technical Summary

Benefits of technology

[0006] The present invention relates to systems and methods for the multifocal imaging of biological materials. An optical system is provided in which a plurality of optical pathways are used in combination with focusing optics to provide a plurality of focal locations within a region of interest of a material being optically measured or imaged. The detector can comprise a plurality of detector elements which are correlated with the plurality of focal locations to provide for the efficient collection of light from the material being imaged. A preferred embodiment of the invention utilizes a scanning system that provides relative movement between the material and the focal locations to provide for fast imaging of the material.

Problems solved by technology

An important issue in the collection of light from discrete focal spots or locations within a turbid medium such as tissue is the cross talk that can occur due to the scattering of light.

This cross talk can substantially limit the usefulness of the images of the tissue that are produced.

By increasing the distance between adjacent focal spots such cross talk can be reduced or eliminated, however, this reduces the resolution of the resulting image or increases the time needed to scan the tissue.

Equally importantly, traditional 3D microscopes sample only tens to hundreds of cells and can never achieve comparable statistical accuracy and precision in many biomedical assays as techniques such as flow cytometry and image cytometry.

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