Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
  • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
  • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
  • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission

Definitions

• the present invention relates to the field of endoscopic imaging devices based on the analysis of tissue autofluorescence induced by light excitation, for example by laser excitation.
• tissue autofluorescence To avoid the harmful effects of these markers, we then looked at the analysis of tissue autofluorescence. Initially, research was mainly carried out on brain tissue or the lungs.
• EP-A-512965 proposes an excitation at 442nm or 405nm. This document criticizes the previously proposed methods operating with respect to responses obtained at two or more wavelengths and proposes an exploitation by visual or mathematical combination of filtered images in bands of different wavelengths to distinguish normal tissues from tumors. . This same document EP-A-512965 indicates that the in vivo responses differ from the in vitro responses and that, moreover, this analytical technique exhibits great sensitivity as a function of the operating conditions.
• US-A-5201318 proposes a method of analysis by excitation of tissues in a wide range of 250 to 500nm, in steps of lOnm, collecting autofluorescence emissions in a range from the wavelength excitation plus lOnm at 2 times the excitation wavelength minus lOnm, in 5nm steps, establishment of an average of the emission spectra thus detected, then processing.
• This document concludes that the analysis technique by measuring the autofluorescence is very complex since the emission spectrum depends very much on the excitation wavelength.
• US-A-5201318 adds that it is necessary to register any possible pair of excitation wavelength and resulting emission wavelength to arrive at a diagnosis.
• the teaching of document US-A-5201318 leads to a complex visualization of the analysis results in three dimensions.
• the present invention aims to improve the state of the art in order to allow the production of a simple device allowing the early detection of cancerous or precancerous surface lesions easily and reliably.
• This object is achieved according to the present invention thanks to an endoscopic imaging device characterized in that it comprises:
• - means suitable for applying, endoscopically, to tissue to be imaged, an excitation signal of wavelength between 300 and 320 nm, preferably between 303 and 313 nm, - means capable of detecting a signal d autofluorescence generated by the tissues, following excitation, and
• the endoscopic imaging device in accordance with the present invention offers valuable assistance in the early diagnosis of superficial cancerous or precancerous lesions. Indeed, a ratio of the order of 1 between the autofluorescence response of NADH and the autofluorescence response of tryptophan is significant for healthy tissue, while a ratio much less than 1 is significant for tumors.
• FIG. 1 shows a schematic view of an endoscopic imaging device according to the present invention for point-by-point observation
• - Figure 2 shows the autofluorescence curves obtained using an imaging device endoscopy according to the present invention, respectively on a healthy wall and on a tumor
• FIG. 3 shows a schematic view of an imaging device according to an alternative embodiment of the present invention, for imaging an area of the tissues observed.
• FIG. 3 shows a schematic view of an imaging device according to an alternative embodiment of the present invention, for imaging an area of the tissues observed.
• the endoscopic imaging device essentially comprises:
• the excitation means 10 are suitable for applying endoscopically, to the tissues T to be imaged, an excitation signal of wavelength between 300 and 320 nm, very preferably between 303 and 313 nm.
• excitation means 10 comprise a source 12 associated with a flexible optical conduit 14.
• the excitation light source 12 can be the subject of numerous variants. It may, for example, be a pulsed UV laser with an XeCl excimer, or a xenon lamp with a quartz envelope followed by a bandpass filter, or alternatively any equivalent means consisting of a source emitting sufficient of light between 300 and 320 nm.
• the conduit 14 is preferably formed of silica fibers. Such fibers are well suited for the conveyance of ultraviolet wavelengths. It should also be noted that optical fibers adapt well to medical techniques, in particular to endoscopy techniques because of their flexibility.
• the optical guide 14 can be formed, for example, from six emitting fibers 14 with a core diameter of 200 ⁇ m, arranged at the entrance to the conduit 14, adjacent to the source 12, in the form of a central fiber 14a surrounded by five fibers 14b.
• the detection means 20 essentially comprise, according to the particular assembly of FIG. 1, a flexible optical conduit 22 associated with a spectrometer 24 followed by a detector.
• the optical conduit 22 is advantageously formed of a multifiber catheter composed for example of thirteen receiving fibers. As can be seen in detail B in FIG. 1, at the distal end the thirteen receiving fibers 22 are arranged in the form of a central fiber 22a surrounded by the six emitting fibers 14, themselves surrounded by the twelve receiving fibers additional 22b.
• the invention is not however limited to these particular arrangements of optical fibers, both for excitation and for detection of the emission.
• the invention is not limited to a concentric arrangement of the fibers used for excitation and of the fibers used for detection.
• a different arrangement of fibers can be used.
• the same fibers can be used to ensure both excitation and detection, for example by separating the excitation beam from the emission beam by a dichroic mirror or an equivalent means.
• the thirteen fibers 22 are arranged in the form of a rectilinear row compatible with the entry slit of the spectrometer, as seen in detail C in FIG. 1.
• a such a catheter allows optimum coupling with the spectrometer 24 and a significant reduction in the number of optical elements used compared to certain devices of the prior art.
• this configuration combined with the excellent qualities of the detector gives the whole apparatus very high sensitivity.
• a filter 26 may be disposed between the proximal end of the optical guide 22 and the spectrometer 24.
• the detector located downstream of the spectrometer 24 may be formed of a strip of photodiodes.
• the spectrometer 24 and the associated detector make it possible to detect the autofluorescence signal generated by the tissues T following the excitation of 300 to 320 nm.
• the analysis and processing means 30 are suitable for isolating the autofluorescence responses generated on the one hand by tryptophan around 370 nm and, on the other hand by nicotine amide adenine dinucleotide (NADH) around 450 nm and treating these two answers to define an image of the tissue analyzed.
• NADH nicotine amide adenine dinucleotide
• the means 30 are preferably adapted to detect the autofluorescence response in the range from 360 to 380 nm (tryptophan) and in the range from 440 to 460 nm (NADH).
• the processing means 30 comprise for example a multichannel analyzer making it possible to take up a complete fluorescence spectrum in a single laser shot of 20 ⁇ J and of a few nanoseconds.
• a preferential treatment in the context of the present invention consists in making the ratio of the intensities 450nm / 370nm and in selecting the ranges where this ratio corresponds to the tumor tissues.
• Such a treatment with respect to intensities makes it possible to eliminate numerous parasitic parameters.
• the inventors have in fact determined that for an excitation between 300 and 320 nm, preferably at 308 nm, there is obtained both a fluorescence signal corresponding to tryptophan, for wavelengths less than 400 nm, around 370 nm, and a NADH fluorescence band centered at around 450nm. The existence of these two signals allows an analysis of the spectra in relative intensity.
• the ratio of fluorescence intensities at 450nm and 370nm is close to 1 for healthy tissue and less than 0.5 for tumor tissue.
• the spectrometer 24 can be replaced by optical bandpass filters specific to the ranges 360- 380nm and 440-460nm. It is thus possible to provide two optical band pass filters placed opposite respective photodetectors or even a single photodetector placed behind an assembly comprising two band pass filters movable alternately opposite said photodetector.
• FIG. 3 shows a UV lamp 10 placed on the proximal end of a fiber 14.
• the fiber 14 makes it possible to excite an area of the tissues T to be observed.
• the fiber 14 is placed in the lighting channel of a conventional endoscope 16.
• the imaging path of the endoscope, formed of optical fibers 22 and adapted to observe the response of said zone to the aforementioned excitation, is as for it directed towards a detection device 20.
• This device 20 preferably comprises a set of filters 27, 28 specific to the bands 360-380nm and 440-460nm (for example filters 27, 28 mounted on a rotary assembly) placed in gaze from a photodetector 29, preferably of the CCD camera type.
• the output of the CCD camera is directed to the processing means 30.
• the CCD camera 29 can be placed at the end of the distal end of the endoscope, that is to say inside the body observed.
• the present invention thus provides valuable diagnostic assistance by superimposing contours of the tumor area (s) on a conventional video image observed by the doctor.
• the present invention leads to a portable device and to implementation compatible with the uses in hospital environments.
• the endoscopic imaging device in accordance with the present invention finds particular application in the field of urology, but also in other fields such as ENT, gynecology (precancer of the cervix), in gastro -enterology, etc.
• the present invention allows early endoscopic detection of surface cancerous or precancerous lesions (severe dysplasias, carcinomas in stitu) which are flat lesions often not detectable by conventional endoscopy, and whose prognosis is severe. These lesions, which it is essential to be able to detect at the earliest, can be asymptomatic for a long time and the clinical signs which accompany them are often not specific.
• the present invention which proceeds by tissue autofluorescence analysis makes it possible to avoid the use of exogenous fluorophore which is often not very selective and dangerous for the patient.
• the device according to the present invention uses a non-ionizing and non-invasive excitation light. It thus offers the possibility of long-term follow-up that is safe for the patient.
• the device according to the present invention is relatively inexpensive and compact.
• the imaging device according to the present invention can be used by natural or artificial routes.

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• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• Medical Informatics (AREA)
• Biophysics (AREA)
• Pathology (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Heart & Thoracic Surgery (AREA)
• Physics & Mathematics (AREA)
• Molecular Biology (AREA)
• Surgery (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
• Endoscopes (AREA)

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• 1995
  • 1995-08-16 FR FR9509833A patent/FR2737845B1/fr not_active Expired - Fee Related
• 1996
  • 1996-08-14 JP JP9508994A patent/JPH11511048A/ja active Pending
  • 1996-08-14 EP EP96929341A patent/EP0850012A1/de not_active Withdrawn
  • 1996-08-14 WO PCT/FR1996/001288 patent/WO1997006724A1/fr not_active Application Discontinuation

Non-Patent Citations (1)

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