Method for diagnosing proliferation regions and device for realizing the same

• US 6,584,342 B1
• Filed: 07/02/2001
• Issued: 06/24/2003
• Est. Priority Date: 02/12/1999
• Status: Expired due to Term

• Current Assignee: Alexandr V. Vinogradov, Alexei I. Trushin, Mikhail L. Stakhanov
• Original Assignee: Alexandr V. Vinogradov, Alexei I. Trushin, Mikhail L. Stakhanov
• Inventors: Trushin, Alexei I., Vinogradov, Alexandr V., Stakhanov, Mikhail L.
• Primary Examiner(s): Walberg, Teresa
• Assistant Examiner(s): ROBINSON, DANIEL LEON
• Application Number:
  US09/869,645
• Time in Patent Office: 722 Days
• Field of Search: 600/476, 600/300, 600/407, 382/128, 128/633, 128/634, 128/665
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0064 Body surface scanning

Abstract

Non-invasive, contract-free method for the diagnostics of the proliferation areas of biological tissue and their localization zones n vivo in a live organism on the basis of visualizing the fluorescence of endogenous porphyrins and a device for implementing this method. Tissue is irradiated with low intensity monochrome radiation in the wave length band of 630 to 645 nm and the fluorescent image is recorded within the band of 650 to 730 nm. Recording is carried out in one or several cycles, the brightness values of the corresponding points in the images are averaged for all recording cycles, the significant brightness range of the averaged image is established and broadened by way of re-calculation with regard to the entire dynamic range of the display device. A color reference image of the tissue and auxiliary images are recorded additionally at the excitation wave length and at the fluorescence wave length with illumination from the corresponding sources, and the fluorescent images of the natural proliferation areas of the same patient and a fluorescing test object are recorded. The device for implementing this method contains an additional laboratory premises lighting source.

Claims

1. Proliferation area diagnostics method the essence of which is in radiating tissue surface under examination with the radiation inducing the internal fluorescence of endogenous porphyrins and their complexes with proteins and recording the fluorescence of endogenous porphyrins and their complexes with proteins the distinctive feature of which is that the tissue segment under examination is irradiated with an even monochrome radiation beam in the wave length band of 630 to 645 nm, the fluorescent image of the tissue segment under examination is recorded only in the spectral wave band of 650 to 730 nm, and proliferation intensity change areas are determined by formal signs in the fluorescent image.

2. Method as indicated in claim 1, the distinctive feature of which is that the duration of exposure and recording the fluorescent image is chosen on the basis of the fluorescent signal intensity level, recording is carried out in one or several cycles the duration of each of which is determined on the basis of the dynamic range of the recording device, and the number of cycles is determined on the basis of the required degree of statistical averaging of noise;

the resulting fluorescent image is produced by averaging the brightness values of the corresponding image points produced in all recording cycles, establishing the significant brightness range of the averaged image and broadening this range by re-calculating with regard to the entire dynamic range of the information display device.

3. Method as indicated in claim 1, the distinctive feature of which is that the tissue segment under examination is illuminated with white light additionally, before or after recording the fluorescent image, with monochrome radiation source being switched off;

the colour reference image of the tissue segment is recorded with the same angle and scale as in the case of recording the fluorescent image, and proliferation area localisation points are established by comparing the fluorescent image with the colour reference image with the use of the coordinate grid and reference points applied to the images or by overlaying the images.

4. Method as indicated in claim 1, the distinctive feature of which is that the first auxiliary fluorescent image, the fluorescent image of the test object, is recorded additionally with the use of the same equipment, in the same spectral band, in the same scale and for the same wave length, density, power of and exposure to radiation inducing fluorescence as in the case of recording the fluorescent image of the tissue under examination, the test object being a cassette containing several compartments filled with a stable fluorophore solution with known concentrations which differ by a known number of times from one compartment to another;

the fluorophore solution should have the spectral bands of excitation and fluorescence which are similar to those of the endoporphyrins and their fluorescing protein complexes to be identified in the tissues under examination, and have the absorption and scattering values in the spectral bands under consideration which are similar to the corresponding values of the tissues under examination. Then the brightness values of particular segments of fluorescent images of the tissue under examination and the first auxiliary fluorescent image are compared and the concentration of endogenous porphyrins and their fluorescing complexes with proteins in the tissue under examination is assessed.

5. Method as indicated in claim 1, the distinctive feature of which is that the second auxiliary fluorescent image, the fluorescent image of a natural proliferation area of the same patient, is recorded additionally, with establishing contrast between the segments corresponding to actively proliferating tissue and adjacent slightly proliferating or non-proliferating tissues, as well as the brightness gradient between them, comparing with contrast and brightness gradient at the fluorescent image of the tissue under examination;

in order to determine contrast and brightness gradient in fluorescent images, the brightness values averaged during the recording period, as well as the brightness values averaged by the space corresponding to the tissue segments under examination are used, and the degree of proliferation of the tissue under examination is assessed with regard to the results of such comparison.

6. Method as indicated in claim 1, the distinctive feature of which that the third and fourth monochrome images of the tissue under examination are recorded with the same angle and scale as in the case of recording the fluorescent image;

the third auxiliary image is recorded at the wave length of the source of radiation inducing fluorescence concerned with even illumination of the tissue under examination by the source, and the fourth auxiliary image is recorded in the spectral band in which the fluorescent image is recorded, but with even illumination of the tissue under examination with an additional source which operates in the same spectral band, and then the third and fourth monochrome auxiliary images are used to assess the optical absorption and scattering values of the tissue segment under examination in the spectral bands corresponding to the excitation and fluorescence bands of endogenous porphyrins and their fluorescing complexes with proteins concerned;

local changes in optical absorption and scattering values are located by comparing the third and fourth monochrome auxiliary images a with the fluorescent and colour reference images of the tissue under examination with the use of a coordinate grid, reference points applied thereon or by overlaying them on each other.

7. A device for proliferation area diagnostics which comprises a monochrome source of the radiation inducing the fluorescence of endogenous porphyrins and their complexes with proteins, a fluorescent image recording unit, a reference image recording unit, a computer with graphical information display, output, documenting and storage devices the distinctive feature of which is that the monochrome source of radiation inducing the fluorescence of endogenous porphyrins and their complexes with proteins radiates in the wave length band of 630 to 645 nm, the fluorescent image recording unit is made in the form of a monochrome CCD-camera with variable frame exposure time and comprises additionally a white light source for illuminating the tissue surface under examination when recording colour reference image, a unit for switching radiation sources and making a collinear configuration of rays, a unit for collinear illumination of the tissue under examination and receiving reflected signals and the fluorescent signal, an image splitting unit, a radiation filtration unit, a video, synchronisation and control signal processor linked to a computer, the fluorescent image recording unit, the reference image recording unit, the unit for switching radiation from sources and making a collinear ray configuration, the radiation filtration unit and the radiation sources.

8. Device as indicated in claim 7, the distinctive feature of which is that it comprises additionally a source of monochrome radiation in the wave length band of 650 to 730 nm for illuminating the tissue under examination when recording the monochrome auxiliary image linked to the video, synchronisation and control signal processor.

9. Device as indicated in claim 7, the distinctive feature of which is that it comprises additionally a laboratory premises lighting source which operates in the visible spectrum band, does not radiate in the wave length band of over 650 nm and is linked to the video, synchronisation and control signal processor.