DE19548913A1 - Diagnostic device for photosensitised reaction in living tissue - Google Patents

Abstract

The device exposes the tissue (7) to incoherent light in the 380-680 nm wavelength range from e.g. a Xe discharge lamp system (6) via an optical cable (5) and connector (2). The degree of spectral internal transmittance of the imaging lens (31), lightguide (32), eyepiece (4) and video camera (8) is matched to the fluorescence spectrum of the photosensitiser or tissue. Between the lamp and cable a system (9) combining a thermostable interference filter (91) and a heat protection filter (92) is interposed. Another filter (93) is placed in front of the camera or eyepiece. A control unit (10) may synchronise a flashlamp source with the optical integration phase of a CCD chip in the camera.

Description

Technical field

The invention relates to a device for in Vivo diagnosis using a photosensitizer sator light-induced reaction in biological tissue.

State of the art

The Diag executed with such a device Nose procedure is in medical jargon also called photodynamic diagnosis (PDD). It is also known to use photosensitizers use photodynamic therapy (PDT). For this reference is made to WO 93/20810, to the rest with regard to the explanation of all here terms and process steps described is expressly referred to.

It has been suggested whether it is possible to have one endoscopic photodynamic diagnosis and therapy with perform a device in which as a light source a krypton laser with a wavelength of approx. 410 nm and a power of more than 200 mWatt is used becomes. The light from this laser is over a quartz light guide with a small numerical aperture through a Endoscope to the areas to be irradiated body.  

To a light-induced reaction in biological systems triggers a patient's photosensitivity sator that like either a hematoporphyrin backbone has the substances Photofrin and Photosan-3, or Delta aminolevulinic acid (ALA), which has recently been used in the Urology and dermatology are used in one Administer concentration of a few mg / kg body weight not. The hematoporphyrin derivatives become intravenous administered, delta-aminolevulinic acid, however, can applied locally, d. H. it is used as a solution to instilled in the bladder for example. These substances now accumulate in tumor tissues in over 10-fold increased concentration. This preferred enrichment in the tumor tissue provides the crucial basis for the photodynamic diagnosis and the photodynamic Therapy.

For diagnosis, the tissue to be examined is approximately 2-12 Hours after administration of the photosensitizer (ALA) endoscopically irradiated with violet laser light. The porphyrin derivatives found in the tumor tissue in a increased concentration are present through this Light stimulated and then exhibit a typical Red fluorescence through which the tumor is localized can be.

In photodynamic therapy, irradiation with red laser light is carried out, since this light with a wavelength of more than 630 nm reaches a depth of penetration into the tissue of approx. 5 mm, in contrast to light of shorter wavelengths, which has a blatantly lower penetration depth . Despite using this optimal wavelength, the indication for photo dynamic therapy is currently limited to flat superficial carcinomas. The biophysical course of the light-induced reaction can be assumed as follows:
The photosensitizer embedded in the tissue is converted into an excited state by the absorption of a light quantum with a defined energy content, which is sent from the respective light source. When irradiated with violet laser light as part of the photodynamic diagnosis, fluorescence radiation is now emitted when falling back to the basic state.

In the case of photodynamic therapy in connection with the irradiation with red laser light high lei the transition from the excited Form into a metastable intermediate state instead of from which the energy caused by decline in the bottom state becomes free, based on molecular oxygen who will carry this energy with the formation of ange lively singlet oxygen. This aggressive Singlet oxygen is destroyed in the tissue in question vital cell structures through photooxidation. This cellular damage along with one simultaneous collapse of the tumor Vascular system to complete tumor destruction (pho totoxic effect).

However, this procedure depends on the used photosensitizers with certain pro afflicted with flowers. When using Photofrin and Photosan-3 as photosensitizers at photodyna mix diagnosis need for fluorescence detection very complex technical devices used  be because of disturbing intrinsic fluorescence only with the help of very complex computer-assisted image ver working techniques and highly sensitive cameras Low light intensifier the fluorescence of the tumor tissue can be demonstrated accordingly. When ver Use of delta aminolevulinic acid is the most induced Fluorescence strong enough that it can be recognized purely visually can be.

But also that achieved by delta-aminolevulinic acid Fluorescence does not lead to an optimal quality of the endoscopic image taken as part of the diagnosis to be drawn. The use of a quartz light conductor with a small numerical aperture for the light Transmission of the laser beam has a very bad one Illumination of the produced image.

By using an additional light guide, that could improve the illumination will be for additional channels lumens available in the endoscope so reduced that the use of other endoscopic instruments is severely restricted.

In addition, in the methods described above for Diagnosis and therapy different lasers or La sources necessary, which on the one hand increases costs gen leaves, and on the other hand, the handling of the endosko system.

Similar problems also occur when implementing the photodynamic diagnosis using a microscope and especially an operating microscope.

Presentation of the invention

The invention has for its object a Direction for diagnosis by means of a photo sensitizer light-induced reaction in biological schem tissue in such a way that the induced Fluorescence while observing the Tissue area of sufficient illumination - without the Use of lasers - can be recognized with high contrast.

An inventive solution to this problem is in Claim 1 specified. Further training of the Er invention are the subject of claims 2 following.

The device for diagnosis according to the invention one light-induced by a photosensitizer Response in biological tissue exhibits an illumination system with at least one light source, one light leading unit that the light of the lighting system aimed at the tissue area to be diagnosed, and an imaging unit that uses the Ge weaving light coming into a proximal image plane depicts. Diagnostic devices with the pre mentioned features are generally known and are for example in endoscopy or microscopy set.

According to the invention - in a manner known per se - uses a broadband light source that is incoherent tes light in the wavelength range from at least 380 to 660 nm generated. This broadband light source can a different spectral distribution than conventional ones in which Have light sources used in endoscopy. If the Light source but also to a conventional sub search of the - also - with photodynamic diagnosis  examined area is to be used preferred if the light source is a conventional one High power light source is like the one used in medicine endoscopy is used. The power consumption the light source is preferably at least 300 watts.

When using "broadband" light sources in the past the problem occurred that the reflected on the tissue area to be examined Light from the light source outshines the fluorescent light.

Therefore, according to the invention, not only the pure transmission degree Ti 1 (λ) of the light-supplying unit is adapted to the fluorescence excitation spectrum of the photosensitizer and the pure transmission degree Ti _b (λ) of the imaging unit is adapted to the fluorescence spectrum of the photosensitizer. Above all, however, the degree of re-transmission of the overall system consisting of the light-supplying unit and the imaging unit, which results from the multiplication of the pure transmittance grades Ti 1 (λ) and Ti _b (λ), has a spectral transmittance of only in a range of at most 50 nm more than 5% and is otherwise less than 5%.

Through this formation of the spectral permeability the light supply unit and the imaging unit unit is achieved that the fluorescent light on the generated by the illuminating light, for example the area around a tumor clearly and with high contrast can be perceived.

To adapt to the different photosensitizers and / or different diagnostic conditions or to convert the device according to the invention  it continues to be a therapeutic procedure preferred if the transmission properties of the light transmitting and the imaging unit by means of one or more optical elements adjustable are.

It is preferred if the setting is such that the intensity of the induced fluorescence zenzlichtes in the same order of magnitude as the Ge velvet intensity of the reflecting part of the light of the lighting system. Particularly advantageous The setting is made in such a way that the two Intensities are roughly the same.

In any case, the device according to the invention has the Advantage that it is to carry out the photodynamic Diagnosis while illuminating the observ ten field as well as for preceding and / or connecting the visual observation of the examined area sufficient to use a single light source. Dar moreover can with the device according to the invention also the photodynamic therapy without changing the Light source, in which case - as already mentioned - the transmission properties the light-transmitting unit the fluorescence spectrum of the photosensitizer are adapted.

The optical elements used to adjust the trans mission characteristics of the light transmitting and the imaging unit used are preferred Filter systems used in lighting and Beo observation beam path can be introduced. Doing so under illumination beam path the beam path from the Lamp of the light source to the light supply unit,  through this unit, and from this unit to the diagno understandable tissue area. The optical Elements and especially the filter systems can print arranged at every point in this beam path be. However, the arrangement is particularly preferred between lighting system and light supplying on unit, for example an optical fiber bundle del. (Without filter system, the pure transmittance accepted as 100%.)

Accordingly, the observation beam path is the Beam path from the illuminated tissue area to the imaging unit and from this to the proximal Understand the image plane. (Without a filter system, too the transmittance is assumed to be 100%.)

If the device according to the invention in an endoscope is integrated, the proximal image plane can be so probably in the endoscope - for example when using it a distal video chip - as well as outside half of the human body. In the latter Trap shows the imaging unit next to an object tiv for example a relay lens system or a Bundle of fibers. When using a relay lens System or a fiber bundle as an imaging unit are broken into the observation beam path filter systems preferred between the "last area che "of the relay lens system or the exit surface of the fiber bundle and the proximal image plane arranges. When integrating the invention Direction into an operating microscope is part of the imaging unit the microscope lens system, the for example, a video recorder can.  

As already stated, the invention achieves that this is due to the tissue area to be diagnosed and of the surrounding area reflected back lighting the fluorescent light does not outshine. For Realization of this basic idea according to the invention it is preferred if that is in the lighting beam lengang and that in the observation beam path each because insertable filter system almost complementary Have filter characteristics. The curves that the Transmission of the two complementary filters in Ab indicate dependence on the wavelength, intersect preferably with a transmission of the individual systems that is less than 50%.

In a further embodiment of the invention the fil that can be inserted into the illumination beam path ter at least two separate filters, one of which Filter a thermostable interference filter and that other filter is a thermostable thermal protection filter. The following are the properties of these two Filters are explained on the condition that as photosensitizer delta-aminolevulinic acid ver is applied. When using a different photosensitive lisators match the filter properties to adapt:

When using delta aminolevulinic acid (ALA) it is preferred if the transmission of the lighting Beam path through a short pass filter in the area between between 380 and 430 nm is at least 50%. At a particularly preferred embodiment is Transmission between 370 and 440 nm at least 95%.  

At a wavelength of 447 ± 2 nm the Transmission 50%. At longer wavelengths it is Transmission is much smaller and is typically less than 1%.

In a preferred embodiment of the invention the transmission both in the wavelength range between 460 and 600 nm as well as between 660 and 780 nm under 1 %. In the wavelength range where mainly Fluorescence light is excited, that is, with Delta-Aminolä vulcanic acid in the wavelength range between 600 and 660 nm, the transmission is less than 0.1%.

This characteristic of the filter system results a light distribution of the illuminating light, the ensures that of the tissue to be examined rich in the wavelength range where mainly Fluorescent light occurs, practically no "non-fluo is reflected back.

Accordingly, the filter in the observation beam path (long-pass filter) has the following characteristics:
T₁ (λ = 370-430 nm) <0.1%
T₁ (λ = 453 ± 2 nm) = 50%
T₁ (λ = 500-1100 nm) 95, preferably 98%

The tolerance for the wavelengths of both filters, at the respective transmission is 50% is before pulls ± 2 nm. This design of the filter is ge ensures that the pure transmission of the entire system only in the range between 430 and 460 nm larger than Is 5%. The maximum value reached in this area should not be more than 15%.  

The use of optical elements and in particular Filters to influence the beam path transmis sioncharacteristics has the advantage that, for example by swiveling out the filter a normal white light Lighting and observation can be done so that the Examiner, for example a doctor tissue area also examined with fluorescence diagnosis u. a. judge by color.

The thermostable heat protection filter used in a preferred embodiment of the invention can have the following characteristics:
T₁ (λ = 370-440 nm) <95%
T₁ (λ = 440-700 nm) ≈ 90%
T₁ (λ = 700 nm) = 50%
T₁ (λ = 720-1100 nm) <1%

The use of a thermostable heat protection filter has the advantage that the interference filter during the Diagnosis is not heated by infrared light. This heating could possibly be the filtercha change the characteristic, the sensitivity of a Reduce camera recording element and light over supporting unit due to the high intensity to disturb.

In any case, it is preferred if the individual Filters only in the respective beam paths if necessary be introduced, their removal from the beam lengang if necessary by a monitoring signal is enabled or prevented.

As a filter, commercially available filters with which he "almost step-shaped" provided according to the invention  Characteristic are used, for example Interference filter, the carrier material of which is quartz.

Known light sources can also be used as light sources and in particular light sources known from endoscopy len are used, the broadband in the above Emit wavelength range light. Such Light source, the light in sufficient intensity is emitted, for example, a gas discharge lamp and in particular a high pressure xenon gas discharge lamp. Should the light output of the Light source may be insufficient, in addition to a "continuously working" light source "pulsed" light source, used as a flash will.

As light-supplying units can - in particular endoscopic applications - commercially available light guides used with at least one fiber, the advantageous ter a numerical aperture of more than 0.45 own, because then an efficient light transport to the area to be diagnosed becomes possible.

Such fibers have a core, for example Quartz and a jacket made of a thermostable mate rial on.

In the case of using an optical fiber, it is preferred if the light source, i. H. so for example assign the gas discharge lamp, a focal spot has a diameter of less than 2 mm through an elliptical reflector is generated, the one numerical aperture for the light emission of more than 0.45. In this case you get a high  efficient coupling between lighting system and light-feeding unit, i.e. the fiber light guide.

A gas discharge lamp can also be used whose focal spot has a diameter of less than 2 mm by means of a parabolic reflector and a focusing unit is focused. The focus Siereinheit is preferably a lens in this case system that has at least one element with an aspheric surface.

In a further preferred embodiment of the Er invention is the lighting system, i.e. the light source and the opti upstream of the light source rule elements, such as filters, etc., designed so that the excitation wavelengths corresponding to each used photosensitizer and each diagnostic tissues are tunable. This Tuning can be done either by appropriate Influencing the light source or by means of pre-form teter filter, such as. B. graduated filters or prisms respectively.

This makes it possible to target different tissues areas to stimulate fluorescence.

The device according to the invention enables both visual observation of the fluorescence as well as the on taking the fluorescence image with a video camera or the like

This video camera or unit is in the image plane the imaging unit arranged. In case of a distal arrangement of the video unit this is in the  Image plane of the lens of the endoscope arranged. in the In case of a proximal arrangement of the video unit this in the image plane of the image relay unit, so the relay lens system or the fiber bundle arranged. Alternatively, the video unit can be so forms that it takes the eyepiece image. With Ver using a microscope as an imaging unit the video unit arranged so that it the ocular image records.

The video unit can in particular (at least) one Have CCD recorders. In this case, it is before moves when the gas discharge lamp ar periodically ar working flash discharge lamp, which is controlled by a tax and evaluation unit is controlled so that the Flash exposure only in the light integra phase of the CCD transducer falls. So that will a highly effective lighting of the examined Range reached without the lighting system and apply too much light energy to the surroundings would hit.

At the same time, a visual observation of the examining area or the light output be increased, it is beneficial if additional a continuously operating light source is provided is.

It is still ahead to control the video signal if the video unit has a variable exposure has setting; so that glare in the Video image can be prevented and you always get one high contrast image showing the fluorescent radiation good reveals. In addition, it is preferred if the  Video unit contains an integration mode with which multiple video images can be integrated.

A device according to the invention which has the features described above enables the fluorescent image to be observed visually by means of the naked eye or a video unit. A particular advantage of the device according to the invention is, however, that the image generated by it allows a largely automated evaluation:
For this purpose, the output signal of the video unit is applied to an image processing system. This image processing system can perform a number of manipulations on the image provided by the video unit:
The color images are captured via the RGB input channels and transformed into the HSI color space
(H = Hue (hue)
(S = Saturation)
(I = intensity).

So it is possible that the image processing system electronically a range of hues in the illustrated Color image fades out to the contrast between below different areas. If the image processing processing system performs an RGB acquisition, so for example, the blue and / or green channel can be switched on and off. This procedure has the Advantage that when switching off the blue and / or green the fluorescence image is particularly clear occurs.  

This emphasis is reinforced by the fact that Image processing system the hidden color channel like a shutter in a monitor shown color image. This results in a particularly "eye-catching" for the viewer Representation, in particular the detection of tumors simplified.

An examination process can proceed as follows:
First, the tissue area to be examined is vi suell examined. This means that a doctor looks at the area illuminated with "wide" light with the eyepiece or on a monitor. To switch to photodynamic diagnosis, the short-pass filter and possibly the thermally stable heat protection filter is pivoted into the illumination beam path, for example by means of a foot switch or a switch on the video camera. At the same time, the green channel and / or the blue channel is switched off periodically. Thus, the doctor sees only the fluorescence image on the monitor and then the superimposition of the fluorescence image with the "normal" image, which is generated by light from the small area in which the transmission of the overall system is not equal to 0.

Furthermore, the image processing system can be used for determining possible tumors, the contrast value to the one individual areas of the image for maximum fluorescence Calculate wavelength. In the case of using Delta aminolevulinic acid (ALA) as a photosensitizer the contrast ratio for the wavelength can be 630 nm calculated for the intensity in the range of maximum 50 nm  net, in which the overall system uses a spectral trans degree of mission of more than 5%.

The device according to the invention can for the various medical examinations.

In addition to the particularly preferred use in endoskopi The device according to the invention can use applications also in connection with a surgical microscope for example in neurosurgery, colposcopy or ophthalmology.

Brief description of the drawing

The invention is described below with reference to an embodiment approximately example with reference to the drawing described in the show:

Fig. 1 shows schematically an apparatus according to the invention for endoscopic applications,

Fig. 2a shows the filter characteristic of the filters used in the various beam paths, and

Fig. 2b, the "total transmission".

Representation of an embodiment

In Fig. 1, an embodiment of a device according to the invention for endoscopic applications is shown schematically. The reference numeral 1 designates an endoscope which in a known manner strikes a light guide 2 , a rod-shaped part 3 which can be inserted into a (not shown) human body, and has an eyepiece 4 .

The light guide connection 2 is connected via a light guide cable 5 to a light source 6 , which can have a xenon discharge lamp, for example. A z. B. consists of a fiber bundle existing light guide 21 in the endoscope 1 that in the light guide 2 a coupled light from the light source 6 to the distal end 11 of the endoscope 1st The light emerging from the distal end 11 illuminates the tissue tissue 7 to be examined.

The light coming from the tissue area 7 enters a lens 31 of the endoscope 1, which is only shown schematically. The image of the objective 31 is passed to the proximal end 12 of the endoscope 1 by an image relay 32 , which may have relay lens systems having rod lenses or a fiber imaging system. The image of the tissue region 7 generated in the proximal image plane 13 can be viewed with the eye through the eyepiece 4 . Alternatively or via a beam splitter in addition to viewing with the eye, the image can be recorded with a video camera 8 . In Fig. 1 the alternative is shown that the video camera 8 is attached directly to the eyepiece 4 .

As far as described above, the structure is at for example by Endo provided with a video camera scope of Karl Storz GmbH & Co., Tuttlingen, German known country. For the detailed structure is therefore on the be known endoscopes from this manufacturer.

To carry out so-called photographic diagnoses can in the illumination beam path and in the observ Attention beam path filter systems are introduced.  

For this purpose, in the embodiment shown in FIG. 1, a filter system 9 is attached to the light output connection 61 of the light source 6 , to which the light guide cable 5 is in turn flanged. The filter system 9 has a thermostable interference filter 91 and a thermostable heat protection filter 92 which is intended to substantially reduce the heat applied to the interference filter 91 . A filter 93 is also attached in front of the video camera 8 .

The exposure setting of the video camera 8 and the light output from the light source 6 are controlled by a control and evaluation unit 10 . For example, the control and evaluation unit 10 can synchronize a flash light source with the light integration phase of a CCD chip in the video camera 8 . Furthermore, the control and evaluation unit 10 can regulate the light output emitted by the light source 6 and / or the exposure setting of the video camera.

The output signal of the video camera 8 is also present at the control and evaluation unit 10 . The evaluation unit can in particular have an image processing system which processes the output signal of the video camera in the manner described in the introduction and represents the image processed output signal on a monitor. Of course, the output directly from the video camera and / or the processed image output signal z. B. stored by means of a recorder and / or stored in an image database or further processed in any other way by means of electronic data processing.

When using a photosensitizer, the tissue area 7 emits both reflected illuminating light and fluorescent light, which is caused by the light-induced reaction by the photosensitizer in biological systems. In order to be able to detect the low proportion of fluorescent light compared to the reflected light and to be able to reliably separate it from the “non-fluorescent light” in particular in the case of subsequent image processing, a suitably chosen transmission characteristic of the illumination and observation beam path is required. Filters 91 and 93 , which can be inserted into the beam path, serve to set the transmission characteristic during photodynamic diagnosis. Since the filters can be removed again, for example, by pivoting them out of the rays, normal observation of the tissue region 7 is also possible without, for example, color falsification.

In the following, the characteristics of the filters 91 and 93 will be explained with reference to FIG. 2 in the case that delta-aminolevulinic acid is used as the photosensitizer. If other photosensitizers are used, the filter characteristics must be adjusted accordingly.

In Fig. 2a, the bold curve shows the transmission (in percent) of the filter 91 as a function of the wavelength (in nm), i.e. the so-called pure transmittance Ti (λ), while the thin curve shows the pure transmittance Ti (λ ) for the filter 93 again.

FIG. 2a shows that the pure transmission of the filter 91 is greater than 90% at wavelengths that are less than about 440 nm. At wavelengths greater than about 460 nm, the transmission is less than 1%. At about 445 nm, the transmission is 50%. Furthermore, in the exemplary embodiment for an interference filter 91 , which is shown in FIG. 2a, the transmission in the range between 600 and 660 nm, in which fluorescent light occurs increasingly, is particularly low and is in particular less than 0.1%. The filter 91 is therefore a short pass filter.

The filter 93 has an almost complementary characteristic:
The transmission T₁ is less than 0.1% at wavelengths between 370 and 430 nm. At a wavelength of 455 nm, the transmission is 50%. At wavelengths between 500 and 1100 nm, the transmission reaches 99% or more.

The transmission curves of filters 91 and 93 intersect approximately between 25 and 30%.

FIG. 2b shows the entire system transmission characteristic of the Ge, which is obtained by multiplication of the curves of the individual filters 91 and 93. As you can see, the transmission is only in the range between 440 and 460 nm over 1% and reaches a maximum value of about 12.5%. This means that only a small part of the illuminating light that is reflected at the tissue area 7 re “reaches” the proximal image plane 13 . The fluorescent light, which is typically emitted at wavelengths between 500 and 780 nm, mostly between 600 and 660 nm, reaches the image plane 13 unhindered, since it only has to pass the long-pass filter 93 , but not the short-pass filter 91 . Although a visual observation of the tissue area 7 is still possible, the fluorescence component of the detected light can be safely separated from the reflected, shorter-wave light.

The above wavelength specifications refer to the use of delta-aminolevulinic acid as a photo sensitizer. When using other photo Sensitizers are the wavelengths at which the individual filters change their pass characteristics, ent adapting accordingly. However, unchanged in essential the property that the two com complementary filter curves for a pure transmission cut less than 50%. Also not The only thing that changes is that the overall system is only in one schma len range, typically 50 nm, if necessary but more or less, is clearly zero is different and in particular is greater than 1%.

If the device according to the invention is also to be used for therapy, the filter system 9 must have a further filter which does not have a short-pass characteristic but a medium-pass to long-pass characteristic.

The above description of an embodiment game that focuses on the use of using Delta aminolevulinic acid as a photosensitizer draws, limits the claims and the description exercise not apparent general inventive idea.

Claims (42)

1. Device for diagnosis by means of a light-induced reaction in vivo in biological tissue by a photosensitizer, with

• an illumination system which has at least one light source with a lamp system ( 6 ) which generates incoherent light in the wavelength range from at least 380 to 680 nm,
• - A light supplying unit ( 2 , 5 , 21 ), which directs the light of the lighting system onto the tissue area ( 7 ) to be diagnosed and / or treated, and
• an imaging, image-capturing and image-transmitting unit ( 31 , 32 , 4 , 8 ) which images the light coming from the tissue area ( 7 ) into a proximal image plane ( 13 ),

wherein the pure transmittance Ti₁ (λ) of the light-guiding unit is adapted to the fluorescence excitation spectrum of the photosensitizer and the transmittance Ti _b (λ) of the imaging unit is adapted to the fluorescence spectrum of the photosensitizer, and the pure transmittance of the overall system consisting of light-supplying unit and imaging unit is only in one system Range of maximum 50 nm has a spectral transmittance of more than 5% and is otherwise less than 5%, based on the above wavelength range. 2. Device according to claim 1, characterized in that the transmission proper light transmission and imaging  Unit using one or more optical elements are adjustable. 3. Device according to claim 2, characterized in that the transmission proper are set so that the total inks intensity of the induced fluorescent light in the same order of magnitude such as the total intensity of the right reflected portion of the light of the lighting system lies. 4. Apparatus according to claim 2 or 3, characterized in that the optical elements are filter systems ( 9 , 91 , 92 , 93 ) which can be introduced into the lighting device and the observation beam path. 5. The device according to claim 4, characterized in that in the lighting Filter system that can be inserted into the beam path Observation beam path insertable filter system have an almost complementary filter characteristic. 6. The device according to claim 5, characterized in that the two complement each other filter curves with a pure transmittance of Cut individual systems of less than 50%. 7. Device according to one of claims 4 to 6, characterized in that the filter system in the illumination beam path Be has at least two filters which can be introduced into the beam path, of which one filter is a thermostable interference filter ( 91 ) and the other filter is a thermostable heat protection filter ( 92 ) is. 8. The device according to claim 7, characterized in that when using delta-aminolevulinic acid as the photosensitizer, the thermally stable interference filter ( 91 ) has the following transmission properties in the visible range:
T₁ (λ = 380-430 nm) <50%
T₁ (λ = 610-650 nm) <1%. 9. The device according to claim 8, characterized in that the blocking factor of the filter ( 91 ) at a wavelength of 630 nm based on the transmission maximum in the pass band at a wavelength of approximately 407 nm is greater than 1000. 10. Apparatus according to claim 8 or 9, characterized in that the thermostable interference filter (short pass filter 91) has the following characteristics:
T₁ (λ = 370 - 440 nm) <95%
T₁ (λ = 447 nm) = 50%
T₁ (λ = 460-600 nm) <1%
T₁ (λ = 600-660 nm) <0.1%
T₁ (λ = 660-680 nm) <1%. 11. The device according to claim 9, characterized in that the tolerance for the wel len length at which the transmission is 50%, ± 2 nm is. 12. Device according to one of claims 8 to 11, characterized in that the thermostable heat protection filter ( 92 ) has the following characteristics:
T₁ (λ = 380-440 nm) <95%
T₁ (λ = 440-700 nm) ≈ 90%
T₁ (λ = 700) = 50%
T₁ (λ = 720-1100 nm) <1%. 13. The device according to one of claims 5 to 10, characterized in that the thermostable inter interference filter ( 91 ) is introduced only for the implementation of the diagnosis in the lighting beam path. 14. Device according to one of claims 8 to 13, characterized in that the filter in the observation beam path (long-pass filter 93 ) has the following characteristics:
T₁ (λ = 370-430 nm) <0.1%
T₁ (λ = 453 nm) ± 2 nm = 50%
T₁ (λ = 500-1100 nm) <90%. 15. The device according to one of claims 8 to 14, characterized in that the pure transmission of the Overall system only in the range between 430 and 460 nm is greater than 5%, and a maxi in this range painting value of not more than 15% reached. 16. Device according to one of claims 4 to 15, characterized in that the removal of the filter ( 91 , 92 , 93 ) from the beam paths is only possible if a monitoring signal enables this. 17. The device according to one of claims 4 to 16, characterized in that the carrier material of the Filter of the filter system is quartz.   18. Device according to one of claims 1 to 17, characterized in that the light source ( 6 ) has little least a gas discharge lamp. 19. The apparatus of claim 18, characterized in that the gas discharge lamp a Xenon gas discharge lamp is. 20. Device according to one of claims 1 to 19, characterized in that the light-feeding unit has a light guide ( 21 ) with at least one fiber, which has a numerical aperture of more than 0.45. 21. The apparatus according to claim 20, characterized in that the core material of the fiber made of quartz and the jacket made of a thermostable mate rial exists. 22. The apparatus of claim 20 or 21, characterized in that the gas discharge lamp of the Lighting system a focal spot with a through knife less than 2mm and an elliptical re has a reflector that has a numerical aperture for the Has light emission of more than 0.45. 23. The device according to claim 20 or 21, characterized in that the gas discharge lamp of the Lighting system a focal spot with a through knife less than 2mm and a parabolic A reflector and a lens system as a focusing unit having at least one aspherical surface.   24. The device according to one of claims 1 to 23, characterized in that the lighting system so is formed that the excitation wavelengths by are tunable. 25. Device according to one of claims 1 to 24, characterized in that a Vi deoeinheit ( 8 ) is arranged in the image plane. 26. The apparatus according to claim 25, characterized in that the video unit ( 8 ) has a CCD sensor, and that the gas discharge lamp ( 6 ) is a periodically operating flash discharge lamp, the flash exposure phase of which controls a control and evaluation unit ( 10 ), that the flash exposure falls only in the light integration phase of the CCD sensor. 27. The apparatus according to claim 26, characterized in that the lighting system too additionally a continuously working light source having. 28. Device according to one of claims 23 to 27, characterized in that the video unit a vari able exposure setting. 29. Device according to one of claims 23 to 28, characterized in that the output signal of the video unit to an image processing system ( 10 ) is attached. 30. The device according to claim 29, characterized in that the image processing system  a range of hues in the displayed color image dazzles. 31. The device according to claim 30, characterized in that the image processing system in the case of RGB processing, the blue and / or green channel switches on and off to increase contrast. 32. Device according to claim 30 or 31, characterized in that the image processing system the hidden color range shutter-like in the shown color image. 33. Device according to one of claims 30 to 32, characterized in that the image processing system performs an HSI transformation. 34. Device according to one of claims 30 to 33, characterized in that the image processing system the contrast value to determine any tumors the individual places of the picture for the maximum fluo Resence wavelength calculated. 35. The apparatus of claim 34, characterized in that the image processing system when using delta-aminolevulinic acid as a photo sensitizer the contrast ratio for the waves length 630 nm to the intensity in the range of maximum 50 nm calculated in which the overall system has a spec has a transmittance of more than 5%. 36. Device according to one of claims 1 to 35, characterized in that the light supply unit and the imaging unit are integrated in a microscope.   37. Device according to claim 36, characterized in that the microscope is a microscope for neurosurgical or ophthalmic sub searches is. 38. Device according to one of claims 1 to 35, characterized in that the light supply unit and the imaging unit integrated into an endoscope are. 39. Device according to claim 38, characterized in that the active light casual total cross-sectional area of the light supply Unit does not exceed 4 mm². 40. Device according to claim 38 or 39, characterized in that the light source is on known endoscopic light source. 41. Device according to claim 40, characterized in that the power consumption of the Light source is at least 300 watts.