Device for the picture-providing diagnosis of tissue

BACKGROUND OF THE INVENTION

[0001] The invention relates to a device for the picture-providing diagnosis of tissue with the selective application of two diagnosis methods, specifically an operating mode for the picture-providing white light diagnosis and an operating mode for the picture-providing auto-flourescence, with a light source whose light is led to the tissue via an endoscope, and with a picture transmission unit arranged in the endoscope which leads the picture of the tissue to a colour camera, wherein the colour camera comprises three sensors for the three colour regions red, green and blue which in each case are in connection with a picture processor unit which provides a monitor with the picture signals.

[0002] The therapy of pre-malignant and early-malignant lesions promises the best chances of healing, whilst the prospects for success with a curative treatment attempt reduces from the stage of the invasive carcinoma. Therefore the diagnosis of pre-malignant or early-malignant tissue is of significant importance.

[0003] From the process of carcinogenesis of the first cell types up to the stage of the invasive carcinoma there extends a time-period of several years. This pre-malignant and early-malignant phase therefore offers a large window for diagnosis in which there is given a successful treatment of the patient and tumour-prevention. Unfortunately this time frame until now for therapeutic purposes could only be insufficiently exploited which is reflected is the small five-year survival rate with patients with a bronchial carcinoma which has remained unchanged for decades. This survival rate as always lies only between 10% and 15%.

[0004] The reason why these exploitation possibilies in the given long time frame have not been sufficient up to now lies in the fact that the sensitivity of the conventional diagnosis forms—this includes among this white light endoscopy—is very small for pre-malignant and early-malignant lesions. Accordingly the detection or localizing and the subsequent therapy of the lesions may not be effected or only in a few cases.

[0005] With the examination of a patient in the bronchial region it is desirable for the physician carrying out the examination firstly to carry out a usual white light diagnosis in order with this under white light to obtain an overview and set up a prior diagnosis. With this one searches for inflammed and malignant tissue as for example exophytic tumours, but also for early-malignant tissue inasmuch as this is visible under white light.

[0006] With the conventional white light diagnosis however often pre-malignant and early-malignant tissue may not often be differentiated from benign tissue which is why it may not be found. The white light diagnosis for this has an insufficient sensitivity. Accordingly the necessity of a life-saving or at least significantly life-lengthening therapy may not be recognized. Here the picture-providing autoflourescence diagnosis represents a decisive advantage. It considerably improves the visibility or the possibility of differentiating pre-malignant and early-malignant tissue with respect to healthy, inflammed or merely metaplastically changed tissue.

[0007] With this with regard to the picture-providing autoflourescence diagnosis with the diagnosis of pre-malignant or early-malignant lesions for their differentiation from healthy tissue one may ascertain the following: healthy tissue differs from diseased tissue on the one hand in the flourecence intensity integrally over the whole emission range, i.e. in the brightness, and on the hand in the fluorescence colour (the integral colour impression created with the observer, caused by a changing weighting of the spectral components in the flourescence light emitted by the tissue).

[0008] With regard to the dependency of the flourescence intensity on the condition of the tissue, FIG. 1 is referred to. Here by way of example for an excitation wavelength of 405 nm the spectral intensity Is over the wavelength W in nanometers is shown for various tissue conditions (Healthy: structured, but healthy tissue as well as macroscopic surface unevennesses, such as possible folds in the tissue with healthy tissue, with regard to the flourescence excitation light and also with regard to the emission of flourescence light act as “light traps” and by way of this reduce the flourescence light detectable by the eye or the camera. Thus this tissue amongst others acts with less intensity similar to diseased tissue.

[0009] The attempt of tissue evaluaton with regard to pre-malignant and early-malignant lesions alone on the basis of flourescence intensity may therefore lead increasingly to results which are wrongly positive and thus lead to a reduced specifity. Under this aspect with the picture-providing autoflourescence for locating pre-malignant or early-malignant lesions the colour of the tissue dependent on the tissue condition or degree of malignancy and the colour impression thus given to the observer play a decisive role. A picture-providing flourescence diagnosis system should therefore be designed such that the colour dependent on the tissue atypia, i.e. the change in the weighting of the spectral flourescence part share, is indeed also made visible to the observer.

[0010] From FIG. 1 however it is also evident that the integral flourescence intensity of early-malignant and malignant tissue with respect to healthy tissue recedes extraordinarily heavily. In combination with the finate or limited dynamics of conventional colour cameras and also of the human eye the colour shifting with respect to healthy tissue under certain circumstances may hardly be perceived or not be perceived at all; the suspected location appears only to be dark, and colour as well as colour shiftings are to be recognized only in a limited manner. An increasing of the brightness only leads to the fact that the healthy tissue surrounding the suspect location acts in an irradiated manner and thus the colour changes, particularly with smaller suspect locations may also not be perceived.

[0011] It is furthermore to be taken into account that the flourescence of pre-malignant and early-malignant tissue (see FIG. 1) which is heavily reduced with respect to healthy tissue leads to the fact that the signals produced by the camera in these tissue regions where appropriate may already be superimposed by a comparitively great noise so that an increase in brightness for example in the form of electronic application, is in any case only possible under certain conditions.

[0012] From this there results problems which may be comparable with those which have already been described above:

[0013] Early-malignant and malignant lesions on account of their greatly reduced flourescence intensity and therefore their colour shifting which is hardly perceivable may hardly be differentiated from that healthy tissue which for example alone, on account of a changed surface structure with regard to the excitation light as well as with regard to the flourescence light produced by way of this, acts in a “light-swallowing” manner and which therefore may supply the observer likewise with less flourescence light than normal structured healthy tissue.

[0014] Insecurity with regard to assessing such tissue in all such cases renders obligatory the taking of a sample, in order to detect where possible all potential early-malignant or malignant sources. By way of this however the false-positive rate i.e. the specifity reduces. To the same extent the time expense rises, and on account of this there arise additional costs and furthermore additional biopsies creating likewise additional costs are necessary. Furthermore each taking of a sample may lead to bleeding which inhibits the further examination.

[0015] On striving to include the colour shifting into the tissue differentiation under the given circumstances it is a disadvantage that with an increasing degree of malignancy or with an increasing atypia of the tissue not only the flourescence in the green spectral region is declining but also the flourescence in the red spectral region—even if less marked (see FIG. 1). From a comprehensive point of view it would however be advantageous when the detected red light with respect to the tissue condition remains unchanged, i.e. remains constant, wherein the red part share led to the observer additionally ideally should be so high that it on the one hand is clearly dominated by signals deriving from the green flourescence of the healthy tissue so that thus the healthy tissue appears green to the user, but that this red part share on the other hand significantly exceeds the signals deriving from the green flourescence of the diseased tissue, which are smaller that those which come from healthy tissue by a factor of 10 (see FIG. 1), so that the diseased tissue appears red to the observer.

[0016] A red part share independent of the condition of the tissue in the above described manner would bring with it the following advantages:

[0017] On the one hand it would lead to an improvement of the colour contrast between healthy and diseased tissue and thus to an increase of the sensitivity, caused by a significantly improved colour shifting towards the red with diseased tissue with respect to the healthy tissue, and on the other hand the weakly flourescing diseased tissue can appear brighter, caused by the then higher red part share. Furthermore a better differentiation of the diseased tissue from that healthy tissue which on account of a microscopically or macroscopically greater structured surface nature swallows light and thus appears darker than “smooth” healthy tissue would be possible; the latter appears dark, the early-malignant and malignant tissue in contrast appears red.

[0018] Since thus the red flourescence according to FIG. 1 does not have a non-negligible dependency on the degree of tissue atypia, specifically recedes with an increasing tissue change just as the green flourescence recedes—even if less pronounced, the provision of a red part share independent of the tissue condition may only be effected via an irradiation of the tissue with additional red light (besides the flourescence excitation light), the red light remitted by way of this from the tissue is in contrast to the red flourescence largely independent on the degree of tissue atypia. At the same time however one must ensure that the signal differences caused by the red flourescence with different tissue conditions are eliminated or at least are almost without significance with respect to the signal in the red channel produced by the red emission.

[0019] From U.S. Pat. No. 5,590,660 there is known a diagnosis system with which red light provided by a light source and then remitted at the tissue goes into the tissue assessment, and specifically additionally to the flourescence light emitted by the tissue. Inasmuch as this is concerned the design of the system and of the light source has been changed so that an improved colour differentiation and thus an improved sensitivity of pre-malignant and early-malignant tissue is achieved with respect to the previous manner of proceeding with which the colour impression and thus the tissue condition are only evaluated on the basis of the autoflourescence of the tissue. However at the same time the manner of proceeding is such that as a detection unit two cameras must be applied, in front of whose sensors there are mounted optical band-width filters which represent specially manufactured products in the context that they do not correspond to the filter specifications of conventional 3-chip cameras suitable for white light endoscopy. The idea on which U.S. Pat. No. 5,590,660 is based is specifically that the whole detected wavelength region is divided up into two separate spectral regions: a first wavelength region in which essentially the whole autoflourescence light lies (wavelengths between 500 nm and 650 nm; according to the sensitivity of the sensors used here the autoflourescence signal detected above 650 nm is disappearingly small), which is led to the first camera whose signals are led to a first colour input of a monitor (e.g. green) and a second wavelength region (which does not intersect with the first wavelength region), in which spectrally there lies the additional illumination light from the light source (red light, wavelengths greater than 700 nm) which after remission at the tissue is led to the second camera whose signals are led to a second colour input of the monitor (e.g. red).

[0020] The manner of proceeding described in U.S. Pat. No. 5,590,660 has the characteristic that the signal supplied to the second colour channel of the monitor is independent of the degree of tissue atypia (with the advantages with respect to the colour differentiation described in detail above) since the detection region of the second camera which delivers signals to this second monitor input lies outside the wavelength region of the emitted tissue autoflourescence signals whose intensity in turn is dependent on the condition of the tissue. To the second signal constant with respect to the tissue condition therefore there may not superimpose a signal which derives from the autoflourescence and which is thus dependent on the tissue condition and the second channel may with a suitable metering of the additional illumination light be used as a colour reference with respect to the tissue condition dependent fluctuations of the signals fed into the first channel.

[0021] On the other hand however with the manner of proceeding described in U.S. Pat. No. 5,590,660 there results the disadvantage that the cameras to be used or their sensors may not be part of a conventional 3-chip camera since the first detection region comprises the wavelength region of the whole autoflourescence light which consists of green light but also of red light, whilst the second detection region may intersect with this first region and accordingly may only lie in the long-wave red spectral region. A conventional 3-chip camera however separates red from green already in a considerably more shortwave region. Thus if with the diagnosis device according to this solution a white light diagnosis is carried out with a 3-chip camera then a further conventional colour camera is necessary. The device of U.S. Pat. No. 5,590,660 is then constructed accordingly complicated and thus for the user is on the one hand awkward and on the other hand is expensive. The fact that the wavelength region led to the first camera is so wide or reaches so far into the red spectral region, has a disadvantageous effect in that the flourescence curves for the different tissue conditions towards the longwave region, in particular however with the beginning of the yellow and red spectral region approach one another more and more and inasmuch as this is concerned the possibility of a tissue differentiation becomes more and more washed out and thus becomes less favourable when the sectoral region led to the first camera reaches into the red.

[0022] Furthermore from U.S. Pat. No. 5,772,580 there is known a diagnosis system which does away completely with the detection of red light with the assessment of tissue, i.e. does away with the red flourescence as well as additional red light provided by the light source and remitted at the tissue. The transmission region of the sensor applied here lies between 480 nm and 600 nm. By way of this although achieving likewise an increased sensitivity for pre-malignant or early-malignant lesions on the other hand there arise the above mentioned disadvantages entailed when one makes do without the red reference, above all the reduced specifity by way of an increased false-positive rate. Although with the device according to this document a white light diagnosis is possible, however for this a second camera is necessary. Furthermore making do without the detection of red light (flourescence as well as red light remitted at the tissue) means a loss of brightness. Thus the system therefore also uses large, heavy and awkward image intensifiers in order to achieve a sufficiently bright picture.

[0023] There are yet known diagnosis devices with which instead of additional red light emmitted by the light source and remitted at the tissue there is detected blue light with the aim of an improved light contrasting of the tissue in the diagnosis mode of the autoflourescence. With this manner of proceeding a smaller part share of the blue light made available by the light source for flourescence excitation which is not absorbed by the tissue but is remitted at the tissue is detected by the camera and not as with the other known systems completely blocked (for example by optical filters). At the same time the blue part share reaching the camera by way of optical filter technology is specified such that healthy tissue appears green to the observer. Whilst diseased tissue appears bluish. The assessment of the degree of disease of the tissue is effected thus essentially by the assessment of the different green-blue part shares. Disadvantageous with this manner of proceeding is the fact that in contrast to red light, blue light has a lower tissue penetration depth. By way of this with the blue light remitted by the tissue the directed reflected part share is larger than with red light, the homogeneously scattered back part share as a result is less than with red light. Since the tissue flourescence light however is emitted relatively homogeneously almost independently of the incidence angle of the excitation light (isotrope) thus the colour impression at the observer arising from the sum of the flourescence and the blue light remitted at the tissue is heavily dependent on the angle of incidence of the excitation and illumination light, and specifically much greater than with the detection of flourescence light and of red light remitted by the tissue. The tissue assessment is thus dependent on the incidence angle of the illumination and excitation light which of course is not at all desirable.

BRIEF SUMMARY OF THE INVENTION

[0024] It is therefore the object of the invention to provide a diagnosis device for the picture-providing diagnosis of tissue—in particular for the examination of the bronchial region—with the selective application of the picture-providing white light diagnosis and the picture-providing autoflourescence diagnosis, with which in the mode of the picture-providing autoflourescence diagnosis on the one hand there is made possible an increased sensitivity, i.e. an improved colour contrasting and thus an improved differentiation possibility between health and pre-malignant or early-malignant tissue, with respect to the manner of proceeding in which in the mode of the autoflourescence diagnosis only the assessment of the autoflourescence light itself is used, and on the other hand permits an increased specifity, i.e. an improved differentiation possibility of pre-malignant and early-malignant tissue above all also with respect to that healthy tissue which on account of its micro-structural and/or macro-structural uneven and therefore light-swallowing surface lead relatively little flourescence light to the receiver and therefore may by error be assessed as diseased tissue. At the same time additionally the colour impression of the tissue arising at the observer in the autoflourescence mode is to be largely independent of the observation angle, i.e. of the angle of the endoscope with respect to the surface of the tissue. Furthermore it is to be possible to be able to fall back on existing diagnosis devices without having to make significant modifications. This means above all things that for both working modes as a detection unit there may be applied a 3-chip camera which is conventional with regard to the optical specifications of the camera head. The retention of the optical specifications means that in the working mode of the white light diagnosis the picture does not undergo any compromise and retains its usual good colour quality. Furthermore the system is to be constructed such that a simple change between the picture-providing white light diagnosis and the picture-providing autoflourescence diagnosis may be realized.

[0025] For achieving this solution the initially mentioned device is characterized in that the light source in the operating mode of the picture-providing autoflourescence diagnosis apart from the flourescence excitation light additionally further emits red light and that the picture processor unit of the camera contains means with which the electrical signals produced by the “red sensor” of the 3-chip camera in the operating mode of the picture-providing autoflourescence diagnosis may be damped. With this, the extent of the damping is coupled to the intensity of the additionally emitted red light, or is dependent on the relation between the flourescence excitation light and additionally provided red light. With this the aim is for the red part share of the light detected by the camera to be practically independent of the degree of the tissue atypia and may be used as a reference with respect to the green part share which is very greatly dependent on the degree of the tissue atypia, in order thus amongst other things to realise an improvement of the colour contrast between benign and pre-malignant or early-malignant tissue. With these measures the sensitivity as well as the specifity of the diagnosis device may be increased wherein in spite of this one may retain a more simple construction with regard to the apparatus and in particular the picture-providing representation in both working modes may be carried out by way of a 3-chip camera which is conventional with regard to the optical properties of the head. The colour reproduction of the tissue in the working mode of the picture-providing autoflourescence diagnosis is largely independent of the angle between the tissue normals and the endoscope.

[0026] As has already been cited the colour impression of the tissue which is based on the degree of the tissue atypia or on the degree of malignancy and conveyed to the observer, in the mode of the picture-providing autoflourescence is based on a heavily increasing decline of the green flourescence and a less strongly pronounced but unfavourably non-negligible decline of the red flourescence with an increasing atypia of the tissue. Healthy tissue then appears green, pre-malignant or early-malignant tissue with a increasing atypia appears increasingly reddish or red-brown. The colour difference and thus the differentiation capability between benign and pre-malignant or early-malignant tissue would however be more pronounced and clearer and thus the sensitivity of the system with regard to pre-malignant or early-malignant tissue or with an increasing degree of malignancy would be increased when the red part share would not likewise reduce with an increasing tissue atypia or with an increasing malignancy degree, but for example would remain constant or at least almost constant and the red part share would be fitting of a reference function with respect to the tissue condition dependent green part share.

[0027] This with the device according to the invention would be increased in that the flourescence excitation light source not only makes available flourescence excitation light—with the autoflourescence excitation in the bronchial region this as a rule is violet/blue light—but yet further additionally red light, and that this is lead to the tissue to be examined.

[0028] Since with the design according to the invention (above all things with respect to the optical properties of the head) conventional 3-chip cameras are used in order thus to permit also an unlimited use of the camera for usual white light endoscopy the light incident in the camera head by way of dichroitic filters is split up into “blue light”, “green light” and “red light” and then led to different sensors (since with the autoflourescence excitation used here practically no blue light is induced the blue channel in this working mode is subsequently not further observed). Firstly however it is of a problem for the described manner of proceeding with autoflourescence diagnosis that the “red sensor” of a 3-chip camera with a conventional camera head, or the optical filter mounted in front of the “red sensor” is specified such that this not only detects the red illumination light which is additionally provided by the light source, remitted by the tissue and independent on of the degree of tissue atypia, in order thus to be able to realise the above mentioned red reference, but simultaneously also the red flourescence light dependent on the malignancy degree, because the transmission region of the optical filter mounted in front of the “red sensor”, this filter determining the spectral detection range of the sensor, begins usually already at wavelengths which are smaller than 600 nm. At these wavelengths the autoflourescence of the tissue is however still not at all negligably small and the signal processed in the red chanel of the camera and made available to the monitor, this signal thus able to be considered as the sum of the flourescence signal and the remission signal, is therefore subjected to fluctuations caused by the condition of the tissue, which lead back to fluctuations of the flourescence light. If inspite of the use of a conventional 3-chip camera a red signal practically independent of the type of atypia of the tissue is to be realized then the part share made available in the red spectral region by the light source is dimensioned so high that the red light remitted by the tissue, whose intensity is independent of the malignancy of the tissue, dominates the red flourescence light dependent of the malignancy degree of the tissue by a multiple factor; i.e. the degree of transmission of the flourescence excitation filter in the light source in the red spectral region is to be selected so high that the red flourescence light with respect to the red light which originates from the light source and which is remitted at the tissue does not play any role or only a negligible role. The larger is the part share of the remission light with respect to the flourescence light of the whole red light detected by the camera, the greater is the independence of the red channel signal led to the monitor on the degree of tissue atypia and thus the better is the possibility of the differentiation of pre-malignant or early-malignant tissue from healthy tissue (greater red shifting at early-malignant or malignant tissue with respect to the benign tissue).

[0029] Simultaneously however in a second step in the diagnosis mode of the picture-providing autoflourescence the red amplification of the camera must be reduced or the red signal damped—according to the intensity of the additional red light or according to the ratio of the flourescence excitation light (in the blue/violet) to the additional red light. The high intensity of the additional red light, which is selected so high that the red flourescence with respect to the red remission at the tissue becomes negligible or almost negligible, and the accordingly strong red remission at the tissue would otherwise—without reduction of the red amplification or without damping of the red signal in the camera—dominate the green flourescence of diseased tissue but also under circumstances also of healthy tissue and the tissue would appear indeed red or at least reddish, the diseased as well as the healthy tissue; there would therefore be almost no or at least a worsened differentiation possibility on account of the transmitted colour impression.

[0030] The reduction of the camera red amplification or the damping of the red signal in the mode of the picture-providing autoflourescence diagnosis is therefore carried out in a manner such that the superposition of tissue flourescence and of red light additionally provided by the light source and remitted by the tissue leads to the healthy tissue appearing green (which is synonymous with a dominance of green flourescence with respect to the red emission independent of the tissue condition—the red flourescence now no longer plays hardly any role) and premalignant or early-malignant tissue appears red (which amounts to a dominance of the red emission independent of the tissue condition with respect to the greatly reduced green flourescence of diseased tissue in comparison to health tissue). Quantitatively therefore the red channel signal determined essentially by red light remitted at the tissue after the damping in the camera lies between the green channel signal which is produced by green flourescence light from health tissue and the green channel signal which is produced by the green flourescence light from diseased tissue.

[0031] This procedure leads in an advantageous manner to a significant increase of the sensitivity for pre-malignant or early-malignant tissue with respect to the case that in the red spectral region only flourescence light and no red light additionally emitted from the illuminating and flourescence exciting light source and remitted at the tissue is detected, which subsequently in the camera is processed further in the above described from.

[0032] The red part share detected by the camera is now no longer or at least hardly dependent on the malignancy degree of the tissue and therefore no longer or hardly reduces with an increasing degree of malignancy, diseased tissue therefore by way of this on the one hand experiences a more clearer red shifting and on the other hand with a suitable setting of the camera damping irradiates more strongly (since the camera damping ideally is set such that the constant red part share remitted by the tissue and constant with regard to tissue atypia produces a clearly stronger signal than the reduced red flourescence with diseased tissue), so that thus not only does the diseased tissue appear in a stronger red but that also the colour of the diseased tissue may be perceived brighter and thus better than when exclusively flourescence light is observed.

[0033] For the formation of the light source there exist various possibilities: According to a first embodiment form it is envisaged that the light source consists of a white light source, i.e. a broad-band lamp emitting over the whole visible spectral region which delivers its light at least partly via an optical filter which permits a light transmission in the blue/violet spectral region and in a spectral region in the red. Alternatively it is provided for the light source to consist of a blue-light filtered white light source and an additional red light source. This additional red light source may for example be a red light laser, e.g. a semiconductor laser, or also a red LED or an array of red LED's. Furthermore the light source may consist of a blue/violet light laser and of a red light laser. In this case for the purpose of carrying out the white light diagnosis furthermore a green light laser may be provided which together with the blue and red laser produces the white light. In order to realise a colour reproduction in the white light mode which is improved with respect to the version with lasers, there may also be used an array of relatively broad-band light diodes emitting in different spectral regions and which as a sum ideally cover the whole visible spectral region.

[0034] With the device according to the invention there is provided an optical (particularly with respect to the optical specifications of the camera head) conventional 3-chip camera. With this it may be the case of a CCD camera or and a CMOS camera. Preferably the means for damping the signal originating from the red picture part share in the mode of the autoflourescence diagnosis are controlled by software so that there is possible a simple, central, processor controlled connection and disconnection of the damping on changing between white light diagnosis and autoflourescence diagnosis. Specifically the means for damping the signal originating from the red picture part share is a voltage controlled amplifier (VCA): Finally between the picture processor unit and the monitor there may be arranged a picture memory which is applied with a picture brightness which is too small.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Further advantageous features of the device are specified in the dependent claims and are described by way of an embodiment example shown in the drawings. In the drawings there are shown

[0036]
FIG. 1 the spectral flourescence intensity Is (random units) over the wave-length W in nanometers for various conditions of tissue.

[0037]
FIG. 2 the course of the curves of the spectral flourescence intensities Is of FIG. 1, standardized to the first flourescence maximum.

[0038]
FIG. 3 schematically the construction of the diagnosis device.

[0039]
FIG. 4 the spectral flourescence intensity Is over the wavelength W in nanometers for various tissue conditions as well as a possible embodiment form of the spectral intensity Is of the red light superimposed on the flourescence, emitted by the light source and remitted by the tissue,

[0040]
FIG. 5 schematically the voltages U for benign and early-malignant tissue produced alone by way of single detection of autoflourescence light from the colour channels (red and green) of the 3-chip camera,

[0041]
FIG. 6 schematically the voltage U for benign and for early-malignant tissue produced by way of detection of autoflourescence light and additionally provided red light from the colour channels (red and green) of the 3-chip camera.

[0042]
FIG. 7 schematically the voltages produced by detection of autoflourescence light and additionally provided red light from the colour channels (red and green) of the 3-chip camera, after damping in the red channel, for benign and early-malignant tissue.

DETAILED DESCRIPTION OF THE INVENTION

[0043] In FIG. 3 there is to be seen the diagnosis device for the combined picture-providing white light diagnosis and picture-providing autoflourescence diagnosis. The device for examining the tissue 1 comprises a light source 2, wherein an incoherent, broad-band light source emitting in the visible spectral region is particularly suitable. The light source 2 emitting preferably white light may be a short arc lamp; here a xenon lamp as well as a gas discharge lamp with mercury part shares or a mercury high pressure or even mercury highest pressure lamp are advantageous. The latter have a broad irradiation base continuum in the visible and the line typical for mercury in the blue and violet. These partly ideally lie in the absorption spectrum for flourescence excitation of the body-intrinsic flourochrome relevant to the autoflourescence diagnosis. Alternatively a halogen lamp is to be considered.

[0044] All mentioned lamps have the advantage that on the one hand they have an irradiation part share in the violet/blue and (even if small with some lamps), part shares in the red, and on the other hand are in the position of emitting white light. These lamps offer thus ideal conditions for a system which is to permit conventional white light diagnosis a well as autoflourescence diagnosis.

[0045] In the examination mode of white light diagnosis the light of the light source 2 via a fibre-optic 15 (single fibre, fibre bundle or fluid light cable) reaches the endoscope 3. For the coupling in of the light into the fibre optic 15 the light source 2 may be designed as a reflector lamp. Conceivable however is also a condenser arrangement. The endoscope 3 leads the light in the known manner to the tissue 1. By way of a picture transmission unit 4 the picture of the tissue 1 via a video objective 16 is led to the camera head 5a of a camera 5 which consists of a camera head 5a and of a camera controller 5b. For this in the picture transmission unit 4 conventional lens systems, GRIN lens systems or picture fibre bundles are used. In order in the mode of autoflourescence diagnosis to make the comparatively weak autoflourescence light visible at all with respect to the strong intensity flourescence excitation light remitted at the tissue, somewhere in the picture channel, for example between the endoscope 3 and the video lens 16 there is incorporated a flourescence excitation light block filter 23 which ensures that the flourescence excitation light remitted at the tissue may not reach the detection unit of the camera. This block filter may either be rigidly attached or pivotable into and out of the beam path.

[0046] With the camera 5 (above all with respect to the optical properties) it is the case of a conventional 3-chip camera which comprises three sensors 6,7 and 8 which are allocated to the three spectral colour regions blue (B), green (G) and red (R). The camera 5 may thus without limitation, above all without comprising the colour reproduction, be used for conventional white light endoscopy. It may be designed as a CCD camera or as a CMOS camera. A beam-dividing unit in the camera head 5a in the known manner for 3-chip cameras breaks up the picture of the tissue 1 arriving here into the three spectral regions “blue” (B), “green” (G) and “red” (R) and image this onto the sensors 6, 7 and 8.

[0047] Via the signal leads 17 the signals of the three sensors 6, 7, 8 are led to a picture processor unit 9. From here the picture signal via a picture memory 14 which need not be activated in the mode of the white light diagnosis, and an interface 18 to the monitor 10, via which the physician may view the picture of the tissue 1. A CPU 19 in the camera controller 5b controls the picture processor unit 9 and the picture memory 14. The picture memory has in combination with the picture processor unit the object in the operating mode of the autoflourescence diagnosis in the case of flourescence signals which are too weak, during the picture integration phase thus when the sensors are not read out, of again and again outputting the previously stored picture with the video frequency. If the illumination or flourescence excitation chain functions efficiently

[0048] The renewed actuation of the switches 21 or 22 ensures that the mentioned measures may be cancelled so that one may switch back from the mode of the picture-providing autoflourescence diagnosis to the white light diagnosis.

[0049] With the described diagnosis device thus in the mode of the picture-providing autoflourescence diagnosis the tissue 1 to be examined in contrast to the “conventional” autoflourescence diagnosis with which only the autoflourescence light itself is detected and assessed—is additionally irradiated with red light and the light remitted at the tissue is used for the tissue assessment whilst retaining the use of a conventional 3-chip camera (conventional camera head, no change of the head filter specifications). In the embodiment example the filter 11 in the light source additionally to the blue/violet light as described transmits red light. Alternatively to the shown construction however also a separate light source, for example a red light laser may be applied.

[0050] For explaining the effect achieved with this firstly FIG. 4 is referred to. Here there are to be seen over the wavelength the spectral intensity Is of the tissue flourescence (triggered by the flourescence excitation light) exemplary for an excitation wavelength of 405 nm for different tissue conditions and the spectral intensity Is of the red light remitted from the tissue (triggered by the red light additionally made available by the light source and led to the tissue), wherein this intensity is superimposed onto the tissue flourescence and is independent of the tissue condition the red light.

[0051] The curves represent the flourescence spectra as they are detected in the camera head. Additionally drawn in and indicated at 24 is the red light which is additionally provided by the light source and remitted at the tissue, as it is detected at the “red sensor” 8 of the camera. The sketched spectral intensity Is of the detected additional red light, i.e. the course over the wavelength, only represents a possible example which meets the demands according to the invention, at the output of the conventional 3-chip camera or on the monitor in the autoflourescence diagnosis mode, of producing a red signal (red reference) practically independent on the degree of tissue atypia. For this the red light which is additionally provided by the light source 2 via the filter 11 or alternatively via an additional red light source, and then remitted by the tissue is selected so strong and intensive that with the red light sum arriving at the “red sensor” 8 of the camera consisting of additionally provided red light remitted at the tissue and of tissue red flourescence produced by blue/violet excitation light, tissue-dependent fluctuations of red flourescence no longer make a difference or hardly make a difference. Thus the larger the light quantity of the additionally provided red light which is remitted at the tissue, the greater is the part share of the remitted red light independent of the degree of tissue atypia of the total red light detected by the camera and thus the less matters the red flourescence on its own and thus also its fluctuations dependent on tissue condition. Therefore with regard to the degree of tissue atypia practically a constant red signal is produced.

[0052] A quantitative upper limiting of the provided additional red light in practice merely has the effect that the “red sensor” is not to go into saturation, i.e. that the red light arriving at the “red sensor” ideally should lie in dimensions of the green flourescence arriving at the “green sensor”.

[0053] In FIG. 6 there are schematically and qualitatively shown the colour signal ratios resulting therefrom in the camera. FIG. 5 represents in contrast the colour signal ratios in the camera with that manner of proceeding with which the tissue is not irradiated with additional red light. The shown voltage ratios for FIG. 5 and 6 as well as for the subsequently explained FIG. 7 are based on the curves of FIG. 1 (flourescence excitation wavelength of 405 nm; in an excitation wavelength region neighbouring this wavelength the results are similar) and the surface part shares limited by the courses of these curves; the influence of the spectral sensitivity of the different components being used and under certain circumstances an accordingly demanded weighting of the curves of FIG. 1 are not taken into account here; this influence however may be corrected to an extensive degree by suitable additional amplification or damping in the individual colour channels.

[0054] In all three figures (5, 6 and 7) the voltages U of the colour channels green (G) and red (G) (as mentioned blue in the mode of the autoflourescence play no role) are shown against one another for benign and early-malignant tissue. With this the suffix “fl” indicates that the voltage originates from tissue flourescence light whilst the suffix “re” indicates that the voltage is based on light remitted at the tissue.

[0055]
FIG. 5 shows the signal voltages U produced in the individual sensors for the case that according to a conventional device one does away with the provision of additional red light. With early-malignant tissue the red signal is comparable to the green signal. The red shifting desired for a good colour contrasting is thus not present with this tissue condition. A red signal amplification is not favourable for two reasons. On the one hand the red signal with healthy tissue is increased by the same factor, which here leads to a reduction in the dominance of the signal produced by the green flourescence light with respect to the signal produced by the red flourescence light—on the monitor therefore the healthy tissue with an increasing red channel amplification appears increasingly reddish, an optimal lifting of the colour contrast is thus not possible in this manner. On the other hand the red flourescence with early-malignant and malignant tissue is weak in intensity and therefore the signal-noise ratio is comparatively small. An amplification of the red channel therefore leads to a worsening of the total picture quality.

[0056]
FIG. 6 shows the signal voltages produced in the sensors for the case that the tissue according to the device according to the invention apart from the excitation light is irradiated with additional red light in the manner that the signal voltage produced by the red light remitted at the tissue clearly dominates that which is produced by the red flourescence light. Onto the signal voltage bar Rfl resulting from the red flourescence there is placed the signal voltage bar Rre resulting from the red light transmission, since the two signal voltages in each case add up.

[0057] With the additional irradiation of the tissue with red light in the above described manner the red light remitted at the tissue is not only much more intensive than the red flourescence but under circumstances is also more intensive or at least of the order of the green flourescence of healthy tissue. If therefore no further measures in the camera were to be made, the tissue imaged on the monitor would always appear red or at least reddish, independent of the condition of the tissue. Thus the additionally sought-after improvement of the colour contrasting of healthy and diseased tissue would not be realized.

[0058] For this reason, according to the invention now after light detection at the camera head and after the light in the sensors has already been converted into an electrical signal, the electrical total red signal, thus the total voltage produced in the “red sensor” of the 3-chip camera, with respect to the electrical green signal, thus the voltage produced at the “green sensor”, by way of the means 12 (see FIG. 3) is damped so much that on the monitor connected to the camera healthy tissue appears clearly green and diseased tissue clearly red.

[0059] The amount of damping of the red part share by the means 12 may be set once and for all before setting the diagnosis system into operation. For example with this one may proceed such that the red damping in the camera controller 5b is set such that the voltage value obtained from the red channel in a first approximation corresponds to the mean of the two voltage values for healthy and diseased tissue at the green channel.

[0060]
FIG. 7 shows the signal voltages produced in the sensors after the red channel voltages of FIG. 6 by way of example have experienced the additionally required damping in a manner such that the benign tissue appears clearly green and the diseased tissue clearly red.

[0061] Therefore now internally in the camera one no longer influences the detected light but the electrical signal produced by the light in the sensors (above all in the “red sensor”). However in the sensor itself or at its output a spectral breakdown of the signal is no longer possible. Instead of this per sensor (red, green, blue) at its output there is in each case only one (time-dependent) signal value. Therefore in the FIGS. 5, 6 and 7 there are only drawn voltage bars. A comparison of FIG. 6 and 7 thus shows by way of example and schematically how the electrical red channel signal with respect to the green channel signal may be set according to the device according to the invention, so that healthy tissue appears green (the voltage at the green channel must clearly dominate the voltage at the red channel) and diseased tissue red (the reduced voltage at the green channel caused by disease must now be clearly dominated by the voltage at the red channel). The comparison of FIG. 5 and 7 shows how with the measures of the device according to the invention with respect to the mere detection and assessment of flourescence light a much clearer colour differentiation of the shown tissue conditions may be realized, in that with early-malignant tissue a significant increase of the red channel signal may be realized, without in the same measure increasing the red channel signal with healthy tissue.

[0062] The setting, by way of example, of the voltage ratios in the camera via the damping member 12 with the result as is shown in FIG. 7, applies only to the theoretically simplest case that in the remaining transmission chain (camera-monitor-human eye) the red signal and the green signal are transmitted in the ratio 1:1. This is not necessarily the case in practice. Accordingly the bar heights represented in FIG. 7 for the different, spectral sensitivities must be corrected. This may likewise be effected via the damping member 12.

[0063] The inclusion of red light remitted from the tissue into the tissue assessment with a simultaneous, accordingly adapted damping of the electrical signals in the red channel of the applied conventional 3-chip camera in the form described here has therefore the following function and advantages: The sensitivity for pre-malignant or early malignant lesions with respect to benign tissue is increased in that the red part share led to the detector from now on no longer or hardly is dependent on the degree of tissue atypia (in contrast to the conditions with the pure flourescence detection) and accordingly ensures an improved colour contrast between benign and early-malignant tissue (the early malignant tissue appears significantly more red with respect to benign tissue).

[0064] The red channel signal with this “fixing” to an almost unchangeable value with respect to the degree of tissue atypia has a reference function. Only the change in green flourescence for the tissue assessment is of importance since indeed ideally the red light led to the camera and thus the observer is almost independent on the tissue condition and is almost constant with regard to this. With a suitably set damping the signal provided from the green channel with healthy tissue is significantly greater and this therefore appears in a strong green, with diseased tissue considerably weaker and the latter therefore appears in a strong red.

[0065] If one would alone take this aspect into account (that anyway only the change of the green flourescence is observed) a complete fading-out of the whole red light would be an alternative to the explained manner of proceeding. The additional effort of fixing filter specifications for the excitation light filter in the red or alternatively an additional red light source whilst maintaining the usual filter specifications as well as an adaptation of the camera to the changed conditions caused by the additional red light would therefore be omitted. The colour impression or the colour shifting in turn would however no longer play a role in the assessment of the tissue, only the drop in intensity in the green would be relevant to the tissue differentiation. As however has already been mentioned, also healthy tissue whose surface on account of morphological unevennesses acts as a “light trap” may cause a similar drop in flourescence as with pre-malignant or early-malignant tissue, with the result that here a differentiation is hardly possible, which then leads to a drop in the specifity. If however remitted red light in the described manner is included in the tissue assessment, the tissue assessment to the first degree takes place by way of the colour impression given to the observer. This is independent of the surface structure of the tissue since the light trap effect with red light and green light is effective to the same extent, thus is independent of the wavelength and independent of the distance of the endoscope to the tissue. As desired thus alone the degree of tissue atypia effects a colour change. Inasmuch as this is concerned the additionally detected, remitted red light has an important reference function in comparison to a complete foregoing of all red light detection.

[0066] Finally the additional red light which is made available by the light source and which is remitted by the tissue in contrast to the measure of completely blanking-out the red light but also—as already explained—in contrast to the mere detection of flourescence light over the whole spectral region (green and red flourescence light) has an additional gain in brightness. In contrast to the latter case there exists the possibility by increasing the red light part share given out by the light source and remitted at the tissue of accordingly reducing the red amplification of the picture-recording camera almost to any extent and thus of improving the signal-noise ratio in this spectral region. This is of great importance against the background of flourescence pictures which are in any case weak and the low sensitivity of common commercial medical cameras in the red region which is as a rule very small with respect to the sensitivity in the green (region) (usually caused by way of an optical filter which is attached on the camera head input and which has with a reducing transmission towards to long-waved red region. Therefore without other measures which limit the picture quality such as electronic amplification or increasing the picture integration time an increase in the brightness in the autoflourescence mode and an improvement of the signal-noise ratio may be achieved.

[0067] A further advantage of the described arrangement—in particular with respect to the diagnosis system described in U.S. Pat. No. 5,590,660 lies in the fact that the light producing the green channel signal is determined by the comparatively narrow transmission band of the optical filter in front of the “green sensor” of a 3-chip camera which is conventional with regard to the head specifications. The long-wave transmission “edge” of this filter lies usually in a spectral region of about 580 nm. Only in one region below this wavelength are however the intensity differences between the benign and pre-malignant or early-malignant tissue greatly distinguished; towards the long-wave (region) the values for the spectral intensity with healthy and diseased tissue approach one another more and more (see FIG. 1). The additional inclusion of light above a wavelength of approx. 580 nm into the green channel as this is provided by the diagnosis system of U.S. Pat. No. 5,590,660 (here up to 650 nm) therefore leads to the fact that the contrast between healthy and diseased tissue increasingly worsens (with an increasing wavelength) and the possibility of tissue differentiation becomes less favourable.

[0068] The device described for realizing the explained manner of proceeding permits further in an advantageous manner the use of a (single) conventional 3-chip camera for both operating modes (white light and autoflourescence) and thus coherently allows the realization of a simple change between the two operating modes of the white light diagnosis and the picture-providing autoflourescence diagnosis. A special sensor and filter design (in the head of the camera) and thus a deviation of the optical head configuration optimal for white light diagnosis is not required, i.e. the camera produces with respect to the picture and colour quantity unlimited good pictures also in the white light mode. Since the diagnosis device only requires one camera for both diagnosis modi, there is created the precondition for a small, light, handy and inexpensive system which inspite of this has a very good sensitivity and a high specifity.

[0069] Since the light additional to the excitation light in the autoflou-rescence mode and used for increasing the colour contrast lies in the red spectral region the penetration depth is comparatively high, the directed reflected part share is comparatively low and thus the achieved colour impression of the tissue is almost completely dependent on the angle from the endoscope to the tissue normal in contrast to systems which detect blue flourescence excitation light and include this in the tissue assessment. The effect may be further increased in that the spectral band of the red light additionally emitted by the light source is selected narrow and is applied onto the long-waved “edge” of the transmission band of the “red filter” in front of the sensor 8.

Device for the picture-providing diagnosis of tissue

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