Image analysis – Applications – Biomedical applications
Reexamination Certificate
1999-01-27
2003-12-02
Patel, Jayanti K. (Department: 2725)
Image analysis
Applications
Biomedical applications
C345S419000
Reexamination Certificate
active
06658142
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to imaging generally and more particularly to post acquisition image processing generally.
BACKGROUND OF THE INVENTION
Post acquisition image processing is well known in the literature. Publications which describe the general state of the art in post acquisition image processing are : Lim, J. S. “Two dimensional signal and image processing”. Englewood Cliffs, N.J. Prentice Hall. (1990); Russ, J. C. “Image processing handbook”. CRC Press. (1992); Pratt, W. K. “Digital image processing”. NY John Wiley & Sons, Inc. (1991); Rosenfeld, A. and Kak, A. C. “Digital picture processing”. Academic Press. (1976); Castleman, K. R. “Digital Image Processing”. Prentice-Hall Inc. Englewood Cliffs, N.J. (1979).
Imaging which provides information relating to refractive characteristics in a imaged volume is known for extremely limited applications. In microscopy, Smith, Nomarski and Differential Interference Contrast (DIC) imaging is known and is described in the following publications: Nomarski, G. “Microinterferometre differential a ondes polarisees”. J. Phys. Radium 16:9S-11S (1955); Lang, W. “Differential-Interferenz-Miikroskopie”. Carl-Zeiss, Oberkochen (1975); Inoui, S. and Spring, K. S. “Video Microscopy: the fundamentals”. 2nd edition. Plenum Press, NY. (1997). Tanford, C. “Physical chemistry of macromolecules”. John Wiley NY. (1961). Appendix C describes classical Rayleigh interference methods, Philpot and Svenson methods based on schlieren image, Lamm method of line displacement, and Gouy interference method all developed for determination of one dimensional refractive index variations.
Computer analysis of DIC imaging is not readily achieved. Known instances are described in the following publications: Allen, R. D., Allen, N. S. and Travis, J. L. “Video-enhanced contrast, differential interference contrast (AVEC-DIC) microscopy: a new method capable of analyzing microtubule related motility in the reticulopodial network of Allogromia laticollaria.” Cell Motility 1: 291-302 (1981); Cogswell, C. J. and Sheppard, C. J. R. “Confocal differential interference contrast (DIC) microscopy: including a theoretical analysis of conventional and confocal DIC imaging”. J. Microsc. 165:81-101 (1992); Gelles, J., Schnapp, B. J. and Sheetz, M. P. “Tracking kinesin-driven movements with nanometre-scale precision”, Nature 331:450-453 (1988); Hdusler, G. and Kvrner, E. “Imaging with expanded depth of focus”. Zeiss Inform. 29: 9-13 (1987); Preza, C., Snyder, D. L. and Conchello, J-A. “Image reconstruction for three-dimensional transmitted light DIC microscopy”. SPIE 2984:220-231 (1997);.Schormann, T. and Jovin, T. M. “Contrast enhancement and depth perception in three-dimensional representations of differential interference contrast and confocal scanning laser microscope images”. J. Microsc. 166:155-168 (1992).
Computerized ray tracing between discrete refractive and reflective surfaces is extremely well developed, but is not well known in the environment of non-homogeneous indices of refraction. This area is described in the following publications: Hecht E. and Zajac A. “Optics” 2nd ed. Addison-Wesley Reading MA (1997); Jenkins, F. A, and White, H. E. “Fundamentals of optics”. McGraw-Hill, NY (1950) ch.8: Ray Tracing.
Calculation of point spread functions (PSF) is extremely well known as described in the following publication: Born M. and Wolf E. “Principles of Optics” Pergamon London (1959);Goodman J. W. “Statistical Optics” John Wiley & Sons NY (1985); Hecht E. and Zajac A. “Optics” 2nd ed. Addison-Wesley Reading MA. (1997); Gibson S. F. and Lanni F. “Diffraction by circular aperture as a model for three-dimensional optical microscopy”. Opt. Soc. Am. A 6:1357-1367 (1989); Gibson S. F. and Lanni F. “Modeling aberrations due to mismatched layers for 3-D microscopy” SPIE optics in complex systems 1319:470-471 (1990); Gibson S. F. and Lanni F. “Experimental test of an analytical model of aberration in an oil-immersion objective lens used in three-dimensional light microscopy”. J. Opt. Soc. Am. A 8:1601-1613 (1991).
Deconvolution of three dimensional microscopic images having location independent PSF is well known and is described in the following publications, some of them authored by some of the present inventors: Jansson, P. A. ed. “Deconvolution of images and spectra”. Academic Press NY (1997); Agard, D. A. and Sedat, J. W. “Three-dimensional architecture of a polytene nucleus”. Nature 302:676-681 (1984); Agard, D. A., Hiraoka, Y., Shaw, P. and Sedat, J. W. “Fluorescence microscopy in three dimensions”. Methods in Cell Biology 30: 353-377 (1989); Castleman, K. R. “Digital Image Processing”. Prentice-Hall Inc. Englewood Cliffs, N.J. (1979). Correction of telescopic images by the use of suitably distorted mirrors and deconvolution of two dimensional telescope images having location dependent PSF are described in the following publications: Boden, A. F., Reeding, D. C, Hanisch, R. J., Mo, J. and White, R. “Comparative results with massively parallel spatially-variant maximum likelihood image restoration”. Bul Am Astr. Soc 27:924-929 (1995); Boden, A. F., Reeding, D. C, Hanisch, R. J. and Mo, J. “Massively parallel spatially-variant maximum likelihood restoration of Hubble space telescope imagery”. J Opt Soc Am A 13: 1537-1545 (1996); Jansson, P. A. ed. “Deconvolution of images and spectra”. Academic Press NY (1997); Tyson R. K. “Principles of Adaptive Optics” Academic Press NY (1991). Reconstruction of blurred images from point objects is described in the following publications: Carrington, W. A., Lynch, R. M., Moore, D. W., Isenberg, G., Fogarty, K. E. and Fay, F. S. “Superresolution three-dimensional images of fluorescence in cells with minimal light exposure”. Science 268:1483-1487 (1995); Femino, A. M., Fay, F. S., Fogarty, K., and Singer, R. H. “Visualization of single RNA transcripts in situ”. Science 280:585-590 (1998).
SUMMARY OF THE INVENTION
The present invention seeks to provide improved apparatus and techniques for post acquisition image processing.
There is thus provided in accordance with a preferred embodiment of the present invention apparatus for computational adaptive imaging including an image information acquirer providing information relating to the refractive characteristics in a three-dimensional imaged volume, a ray tracer, utilizing the information relating to the refractive characteristics to trace a multiplicity of rays from a multiplicity of locations in the three-dimensional imaged volume through the three-dimensional imaged volume, thereby providing a location dependent point spread function and a deconvolver, utilizing the location dependent point spread function, to provide an output image corrected for distortions due to variations in the refractive characteristics in the three-dimensional imaged volume.
Preferably, the image information acquirer acquires at least two three-dimensional images of a three-dimensional imaged volume, at least one of the two three-dimensional images containing the information relating to the refractive characteristics in a three-dimensional imaged volume.
When the refractive characteristics are extractable from the image to be corrected for distortions, or are known independently, only one three-dimensional image need be acquired.
The acquirer may obtain refractive index information from DIC, for example from phase microscopy or from flourescence -for example in DNA associated stains wherein the stain intensity is proportional to the refractive index increment.
Refractive index mapping may be applied to samples whose refractive index is known. For example this may apply to microchip wafer structures, whose geometry is known.
In accordance with a preferred embodiment of the present invention, the image acquirer acquires at least three three-dimensional images of the three-dimensional imaged volume.
Preferably, the image acquirer acquires a plurality of three-dimensional images of the three-dimensional imaged volume, each the image having a discrete wavelength band.
Alternatively, the image acq
Agard David A.
Hanser Bridget M.
Kam Zvi
Sedat John W.
Choobin Barry
Darby & Darby
Patel Jayanti K.
Yeda Research and Development Co. Ltd.
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