Microscopy system, microscopy method and a method of treating an aneurysm

• US 20040109231A1
• Filed: 08/28/2003
• Published: 06/10/2004
• Est. Priority Date: 08/28/2002
• Status: Active Grant

• Current Assignee: Carl Zeiss Meditec AG (Carl-Zeiss-Stiftung), Klinikum Der Johann-Wolfgang-Goethe Universitã¤T Frankfurt
• Original Assignee: Carl-Zeiss-Stiftung, Klinikum Der Johann-Wolfgang-Goethe Universitã¤T Frankfurt
• Inventors: Hauger, Christoph, Gaida, Gerhard, Haisch, Michael, Wolf, Hartmut, Hug, Joachim, Brigitta, Schwarz, Raabe, Andreas
• Granted Patent: US 7,580,185 B2
• Time in Patent Office: Days
• US Class Current: 359/385
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: G01N 2021/1782 In-depth resolution
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/3563 for analysing solids; Preparation of samples therefor
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G02B 2027/0134 of stereoscopic type
• CPC Class Codes: G02B 2027/0138 comprising image capture systems, e.g. camera
• CPC Class Codes: G02B 2027/014 comprising information/image processing systems
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/18 Arrangements with more than one light path, e.g. for comparing two specimens
• CPC Class Codes: G02B 21/22 Stereoscopic arrangements
• CPC Class Codes: G02B 21/361 Optical details, e.g. image relay to the camera or image sensor G02B21/364 takes precedence; illumination details G02B21/06 and subgroups
• CPC Class Codes: G02B 21/365 Control or image processing arrangements for digital or video microscopes G02B21/361, G02B21/362 take precedence
• CPC Class Codes: G02B 21/367 providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
• CPC Class Codes: G02B 21/368 : details of associated display arrangements, e.g. mounting of LCD monitor
• CPC Class Codes: G02B 27/0172 : characterised by optical features
• CPC Class Codes: G02B 7/002 : Mounting on the human body

Abstract

A microscopy system and a microscopy method are provided for observing a fluorescent substance accumulated in a tissue. The microscopy system comprises a filter allowing to observe the tissue at a same time both with visible light and with fluorescent light. It is possible to observe a series of previously recorded fluorescent light images in superposition with the visible light images. An end of the series of images may be automatically determined. A thermal protective filter may be inserted into a beam path of an illuminating system at such automatically determined end of the series. Further, the fluorescent light image may be analyzed for identifying a coherent fluorescent portion thereof. A representation of a periphery line of the coherent portion may be generated, and depths profile data may be obtained only from the coherent portion. An illuminating light beam for exciting the fluorescence may be modulated for improving a contrast of fluorescent images.

Claims

1. A microscopy system for visualizing a fluorescence of indocyanine green in an object to be inspected, wherein the microscopy system comprises:

a microscopy optics having

a first beam path for optical imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object region with light including wavelengths of a first wavelength range comprising a fluorescent emission wavelength of indocyanine green, and

a second beam path for providing a magnified first representation of the object region, wherein the first representation represents images of the object region with light including wavelengths of a second wavelength range comprising at least visible light;

a display system for displaying a second representation generated on a basis of the first image data in superposition with the first representation for observation by a user; and

an illumination system for providing at least one illuminating light beam directed onto the object region, wherein the at least one illuminating light beam includes light with wavelengths of the second wavelength range and an excitation wavelength of indocyanine green.

2. The microscopy system according to claim 1, wherein the light of the at least one illuminating light beam is emitted from one single light source.

3. The microscopy system according to claim 2, wherein the light source comprises one of a xenon lamp and a halogen lamp.

4. The microscopy system according to claim 1, wherein the illuminating system comprises a first filter disposed in a beam path of the illuminating system, wherein the first filter substantially eliminates light with a fluorescent emission wavelength of indocyanine green from the illuminating light beam.

5. The microscopy system according to claim 1, wherein the illumination system comprises a second filter disposable in a beam path of the illuminating system, wherein the second filter substantially eliminates light from the illuminating light beam having a wavelength higher than 710 nm.

6. The microscopy system according to claim 1, wherein the illumination system comprises a second filter disposable in a beam path of the illuminating system, wherein the second filter substantially eliminates light from the illuminating light beam having a wavelength higher than 690 nm.

7. The microscopy system according to claim 5, wherein at least one of the first and second filters comprises a transmissive filter or a reflective filter.

30. The microscopy system according to claim 1, wherein the first beam path comprises at least one ocular for representing the images.

32. The microscopy system according to claim 1, wherein the first beam path comprises at least one light detecting component of a second camera for generating second image data representing images of the object region with visible light, and wherein the second representation is displayed by the display system.

8. A microscopy system for visualizing a fluorescence of a fluorescent substance in an object to be inspected, wherein the microscopy system comprises:

a microscopy optics having

a first beam path for optically imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object region with light including wavelengths of a first wavelength range comprising a fluorescent emission wavelength of the fluorescent substance, and

a second beam path for providing a magnified first representation of the object region, wherein the first representation represents images of the object regions with light including wavelengths of a second wavelength range comprising at least visible light;

an image memory for storing a set of first image data detected by the first camera during at least a time duration; and

a display system for displaying a sequence of second representations generated from at least a subset of the set of first image data, wherein the sequence of second representations is displayed in superposition with the first representation for observation by the user.

9. The microscopy system according to claim 8, wherein the display system is configured for repeatedly displaying the series of second representations.

10. The microscopy system according to claim 8, further comprising a controller configured to select the subset from the set of first image data based on intensities of the images represented by the first image data of the first set.

11. The microscopy system according to claim 8, further comprising a controller configured for selecting the subset from the set of first image data based on differences of intensities of the images represented by the first image data of the first set.

16. The microscopy system according to claim 11, wherein the intensity modulator comprises a first light source emitting light of the excitation wavelength of the fluorescent substance at modulated intensities.

17. The microscopy system according to claim 16, wherein the illumination system comprises a second light source emitting visible light which is free of excitation wavelengths of the fluorescent substance.

19. The microscopy system according to claim 17, wherein the predetermined wavelength is in a range of one of 690 nm to 720 nm, 720 nm to 750 nm, 750 nm to 780 nm, and 780 nm to 800 nm.

12. A microscopy system for visualizing a fluorescence of a fluorescent substance in an object to be inspected, wherein the microscopy system comprises:

a microscopy optics having

a first beam path for optically imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object regions with light including wavelengths of a first wavelength range comprising a fluorescent emission wavelength of the fluorescent substance, and

a second beam path for providing a magnified first representation of the object region, wherein the first representation represents images of the object region with light including wavelengths of a second wavelength range comprising at least visible light;

an illumination system for providing at least one illuminating light beam directed onto the object region, wherein the at least one illuminating light beam includes light with an excitation wavelength of the fluorescent substance, and wherein the illuminating system comprises a light modulator for modulating an intensity of the light with the excitation wavelength of the fluorescent substance; and

a display system for displaying a second representation generated on the basis of the first image data in superposition with the first representation for observation by a user.

13. The microscopy system according to claim 12, wherein the intensity modulator comprises a filter chopper.

14. The microscopy system according to claim 12, wherein the filter chopper comprises one of a reflective filter and a transmissive filter.

15. The microscopy system according to claim 12, wherein the illumination system comprises a light source emitting light of the excitation wavelength of the fluorescent substance and visible light.

18. A microscopy system for inspecting an object, the microscopy system comprising:

a microscopy optics having a first beam path for optically imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object region;

an illumination system for providing at least one illuminating light beam directed onto the object region, wherein the illumination system comprises a first filter which is positionable at a first position in which the first filter is disposed within a beam path of the illumination system, wherein the first filter eliminates light with wavelengths higher than a predetermined wavelength from the illuminating light beam, and wherein the illuminating system comprises an actuator for displacing the first filter from a second position in which the first filter is not positioned within the beam path to the first position; and

a controller configured for controlling the actuator for displacing the first filter from its second position to its first position based on an analysis of intensities of images represented by the first image data.

20. The microscopy system according to claim 18, wherein the first image data represent images of the object region with light including wavelengths of a first wavelength range comprising a fluorescent emission wavelength of a fluorescent substance accumulated in the object.

21. The microscopy system according to claim 20, wherein the fluorescent emission wavelength of the fluorescent substance is higher than the predetermined wavelength.

22. The microscopy system according to claim 18, wherein the microscopy optics further comprises a second beam path for providing a magnified first representation of the object region, wherein the first representation represents images of the object region with light including wavelengths of a second wavelength range comprising at least visible light.

23. The microscopy system according to claim 22, further comprising a display system for displaying a second representation generated on the basis of the first image data superimposed with the first representation for observation by a user.

24. A microscopy system for visualizing a fluorescence of a fluorescent substance in an object to be inspected, wherein the microscopy system comprises:

a microscopy optics having

a first beam path for optically imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object region with light including wavelengths of a first wavelength range comprising a fluorescent emission wavelength of the fluorescent substance, and

a second beam path for providing a magnified first representation of the object region, wherein the first representation represents images of the object region with light of a first wavelength range comprising at least wavelengths of visible light;

a controller configured for generating second image data representing at least a peripheral line of a coherent portion of the image of the object region, wherein light intensities of the image within the coherent portion exceed a threshold; and

a display system for displaying a second representation generated on the basis of the second image data superimposed with the first representation for observation by a user.

25. A microscopy system comprising:

a microscopy optics having a first beam path for optically imaging an object region onto a light detecting component of a first camera for generating first image data representing images of the object region with light including a first wavelength range comprising a fluorescent emission wavelength of a fluorescent substance;

a controller configured for generating location data representing at least one coherent portion of the image of the object region represented by the first image data, wherein light intensities of the image within the at least one coherent portion exceed a threshold; and

an interferometer apparatus having a beam scanner for scanning the object region with an analyzing beam based on the generated location data, and a radiation detector for obtaining depth profile data representing an intensity of radiation of the analyzing beam received back from the object.

26. The microscopy system according to claim 25, wherein the controller controls the interferometer apparatus such that the interferometer apparatus obtains the depth profile data only in the at least one coherent portion.

27. The microscopy system according to claim 25, wherein the interferometer apparatus includes an optical coherence tomography apparatus.

28. The microscopy system according to claim 25, wherein the microscopy optics further comprises a second beam path for providing a magnified first representation of the object region, wherein the first representation represents an image of the object region with light including a first wavelength range comprising at least visible light.

29. The microscopy system according to claim 28, further comprising a display system for displaying a second representation generated on the basis of the depth profile data in superposition with the first representation for observation by a user.

31. The microscopy system according to claim 29, wherein the display system is configured to superimpose the second representation with the first beam path directed to the ocular.

33. A microscopy method of visualizing a fluorescence of indocyanine green in an object to be inspected, wherein the method comprises:

displaying a representation of a first visible light image for observation by a user;

recording a second image of the object with light including a fluorescent emission wavelength of indocyanine green;

displaying the second image superimposed with the first image for the observation by the user; and

illuminating the object with at least one illuminating light beam containing the visible light and light of an excitation wavelength of indocyanine green.

34. The microscopy method according to claim 33, wherein the at least one illuminating light beam is generated by one single light source emitting the visible light and the light with the excitation wavelength of indocyanine green.

35. A microscopy method of visualizing a fluorescence of an object to be inspected, the method comprising:

displaying a magnified first representation of the object for observation by a user, wherein the fluorescence of the object is substantially not visible in the first representation;

recording a series of fluorescent light images of the object during a time duration; and

displaying the recorded series of fluorescent light images of the object after the time period has lapsed such that the series of fluorescent light images is visible for the user and superimposed with the magnified first representation of the object.

36. A microscopy method of visualizing an object to be inspected, the method comprising:

illuminating the object with light including wavelengths higher than a predetermined wavelength, and recording a series of images of the object during the illumination of the object with the light of wavelengths higher than the predetermined wavelength;

terminating the illumination of the object with the light of wavelengths higher than the predetermined wavelength, based on an analysis of the recorded images, and illuminating the object with light only including wavelengths smaller than the predetermined wavelength; and

displaying a representation of the object illuminated with the light only including the wavelengths smaller than the limiting wavelengths for an observation by the user, and displaying a representation generated in dependence of an analysis of the recorded series of images for the observation by the user.

37. The microscopy method of claim 36, wherein a fluorescent substance is applied to the object when the object is illuminated with the light of the wavelengths higher than the predetermined wavelength.

38. A microscopy method of visualizing an object to be inspected, the method comprising:

illuminating the object to be inspected with light of a first wavelength range comprising visible light;

generating an image of the object with the light of the first wavelength range;

recording an image of the object with light of a second wavelength range which overlaps with the first wavelength range only partially or does not overlap with the first wavelength range;

analyzing the recorded image and identifying at least one coherent portion of the recorded image wherein intensity values of the image within the at least one coherent portion exceed a threshold; and

generating a representation of a periphery of the at least one coherent portion and displaying the representation superimposed with the image of the object in the first wavelength range.

39. A microscopy method, comprising:

recording an image of an object field with light including an excitation wavelength of a fluorescent substance;

analyzing the recorded image and identifying at least one coherent portion of the recorded image, wherein intensity values of the recorded image within the at least one coherent portion exceed a threshold; and

obtaining depth profile data only in an analyzing region determined in dependence of the at least one identified coherent portion, wherein the analyzing region is smaller than the object field.

40. A method of treating an aneurysm of a patient, the method comprising:

clipping the aneurysm;

injecting indocyanine green into the patient;

generating at least one fluorescence image of at least one artery adjacent to the clipped aneurysm; and

assessing vascular blood flow of the at least one artery based on the at least one fluorescence image.