WO1988009145A1

WO1988009145A1 - Arrangement for measuring state values of surfaces of organic tissues

Info

Publication number: WO1988009145A1
Application number: PCT/EP1988/000465
Authority: WO
Inventors: Wolfgang Lohmann
Original assignee: Carl-Zeiss-Stiftung Handelnd Als Carl Zeiss; Carl Zeiss
Priority date: 1987-05-29
Filing date: 1988-05-25
Publication date: 1988-12-01
Also published as: EP0315666A1; DE3718202C1

Abstract

In an arrangement for measuring state values of the surfaces of organic tissues, the light reflected after monochromatic split-image projection (10, 11, 12) from the surface of the tissue is analysed (17, 18) by a recording spectrophotometer (14, 16) in terms of the maximum intensity of the reflected and fluorescent light and the corresponding wavelengths. The state value is represented by paramater sentences formed from the wavelength of the excitation wave, the maximum intensities, and their corresponding wavelengths. The wavelength of the excitation wave is chosen from the range 320-550 nm, and the recorded spectrum is analysed in the range 320-700 nm. The measuring arrangement and the surface of the tissues can be moved relative to each other by means of a drive and a control device (26).

Description

Description:

Arrangement for measuring a condition value for organic tissue areas

The invention relates to an arrangement for measuring a state value for organic tissue areas according to the preamble of claim 1.

Such an arrangement is known from the unpublished patent application P 35 42 167.3. The older application is directed to the measurement of the eye-lens opacity and requires a fixed alignment between the actual measuring device and the measurement object, namely the eye lens. It can be used for measurements in vivo and in situ. Due to the fixation between the measuring object and the measuring device and the exclusive evaluation of the fluorescent light, the. Scope and the significance of the arrangement significantly limited.

The invention was therefore based on the object of changing the arrangement so that its application range is expanded. The extension should both remove the restriction to a very specific measurement object and increase the comparability of the measurement results by supplementing measurement signal acquisition and linking the measurement signals.

This object is achieved according to the invention by the characterizing features of claim 1. Advantageous developments of the invention result from subclaims 2 to 11.

More detailed investigations with the arrangement described in the main application P 35 42 167.3 have shown that the measurement of the fluorescence spectrum not only on the eye lens, but also on other organic tissue areas, in particular skin areas and other cell groups, such as blood cells, significant statements allowed. The excitation wavelength could be extended to the range between 320 nm and 550 nm.

A further finding was that the intensity of the re ﬂ ection light measured at the excitation wave length is also related to the behavior of the examined tissue areas in relation to the emitted fluorescence spectrum. By including this value in the evaluation, the measurement certainty can be increased.

The decisive extension of the applicability to other measuring objects has resulted from the separation of the entire measuring arrangement into a measuring head and a bearing for the measuring objects, both parts being able to be arranged so as to be displaceable relative to one another. To facilitate the adjustment of the measuring head in relation to the object location to be examined, it is advantageous to record the position of the measuring gap with a video camera and to display it on a monitor.

The defined displaceability of the two arrangement parts relative to one another should be possible in three dimensions. Starting from a first measuring position, the measuring device provided according to the invention can then specify both the distance between different measuring positions on the measuring surface and a change in the distance between the measuring head and the tissue surface. The relative displacement can be done manually, but it is advantageously controlled by a motor, which enables an automatic measurement sequence with the acquisition of several comparison values for a tissue surface.

By taking certain reference values into account, the current measured values can be normalized, which simplifies the comparison of the measured values with one another. In the simplest case, the reference values can be based on a single excitation wavelength and both the fluorescence intensity of the the nearest maximum as well as the intensity of the reflection light. In contrast, a comprehensive measurement also takes into account different excitation wavelengths and any fluorescence maxima that may occur.

The standard values can be obtained from general measurements on various similar tissue samples and entered into the memory for further processing. However, they can also be determined individually on a tissue sample to be examined. This is expediently done in the starting position of a sequence of measurements.

The invention is explained in more detail below with the aid of a drawing and schematically illustrated exemplary embodiments. The drawing shows in detail in

Figure 1 is a block diagram of the measuring arrangement;

Figure 2 shows an embodiment with an adjustable measuring head;

Figure 3 shows an embodiment for large object areas;

Figure 4 curves for the reflection and

Fluorescence spectrum at an excitation wavelength λ _A in two different measuring positions and

FIG. 5 shows a representation of the intensity _values I _F of λ _max1 and λ _max2 at the same λ _A as a function of the measurement location X.

The block diagram in Figure 1 is intended to illustrate the interaction of the individual functional elements of the measuring arrangement. The radiation generated by a light source (10) is narrowed to a very narrowly limited spectra range λ _A by a monochromator (11). Various interchangeably arranged narrowband filters can be used as the monochromator, or dispersive elements can also be used. It is also possible to use a line emitter or a continuum emitter as the light source (10).

The connection to the slit projector (12) is expediently made by a flexible light guide (13), so that the

Light source and the monochromator can be installed separately in a fixed position.

A detector unit (14) is assigned to the slit projector (12) in the same structural unit. After a preamplification, your signals are fed to an analyzer (16) via a flexible line (15). As a detector e.g. serve a diode row with an upstream dispersion prism. However, it is also possible to first use the light entry surface of a light guide as a detector, so that this forms the flexible connection to the analyzer (16). A multi-channel analyzer has proven itself as an analyzer. This, like the subsequent evaluation device (17) and the measured value display (18), can then be arranged in a fixed position.

To adjust the slit image on the measurement object, a radiation element (19) is provided in the measurement beam path, which generates an image of the object field on the receiving surface of a video camera. A conventional CCD arrangement, which is spatially assigned to the beam splitter (19), is suitable for this. The image information can then in turn be fed to the camera (21), an image intensifier (22) and a monitor (23) via a flexible line (20). In this way it is possible to make the measuring head (24) with the slit projector (12), the detector (14) and the beam splitter (19) very compact and light, whereby its storage for the relative displacement is considerably simplified. If weight problems and the spatial dimensions of the measuring head play no role, any number of the previously mentioned functional elements can of course be placed in the measuring head to get integrated.

An object table (25) is used to store the measurement object. This can be fixed, so that only the measuring head (24) is moved. However, it can also be displaceable, in which case rough positioning of the measuring arrangement can be carried out, for example, and fine positioning can be carried out by moving the measuring head (24). The measuring device (26) controls the various relative movements, measures the displacement paths and coordinates the measurement signal retrieval.

In Figure 2, the measuring head (24) is attached to a rod (27) adjustable on all sides. The monochromatic light source is e.g. represented as an exit surface (28) of a light guide (13). This illuminates a slit (29), which is imaged by projection optics (30). An imaging optical system (31) is also provided in the measuring beam path, which guides the received radiation via a splitter mirror (32) to a detector (14) and into an observation beam path (33), which is not shown.

The imaging optics (30, 31) define optical axes which intersect in a measuring plane (34), and the measuring head (24) can be displaced via the linkage (27) in such a way that the measuring plane (34) coincides with the plane of the investigating tissue area on the arm of the test subject. The arm can be fixed against the table surface by means of buckles, not shown.

The linkage (27) can, for example, be attached to a cross slide guide (35), the one guide track (36) of which is attached to a table surface (37) which also serves as an object support. The cross slide can be moved in a known manner by motor. A motor (38) is shown, which drives the slide part (39) running in the plane of the drawing. drives. The displacement path in the two coordinate directions of the cross slide can be measured and registered with the aid of path sensors, not shown. If the measuring head has previously been adjusted with respect to the tissue surface, the examined tissue surface area can be specified in terms of size and the local distribution of the natural fluorescence and the reflection light within this surface can be determined in a coordinate manner.

The linkage (27) is fastened in the cross slide guide (35) by means of a column part (40). On the one hand, this can be rotatably mounted about its longitudinal axis, but it can also be equipped with a height adjustment facility. After adjusting the measuring head (24) and fixing the joints of the linkage (27), a topographical statement can also be made within the measuring range on the tissue surface by measuring the height adjustment.

The exemplary embodiment according to FIG. 3 shows a possibility for the arrangement of the functional elements already described, which is suitable for the examination of relatively large objects. The measuring head (24) is suspended via a known one, here e.g. tripod (41) attached to the ceiling, which should also be displaceable on all sides. The person to be examined lies on a trundle bed (42) which should also be measurably displaceable on the table surface (43). It can also be locked in any position. Under the examination table, all the assemblies described in connection with FIG. 1 are housed in a cabinet (44).

With the help of FIG

Skin curves typically occurring measurement curves are described. The measurement was carried out at an excitation wavelength λ _A = 366 nm. The intensities of the backscattered

Spectral components were determined using an optical

Multi-channel analyzer measured, the intensity I as a number of pulses per 100 msec.

The upper diagram in FIG. 4 contains two measurement curves. The lower-intensity lower curve was recorded on a skin surface that shows no atypical discolouration at the measuring point and in its vicinity. The reflection _light I _OR at λ _A and the intensity of the _natural fluorescence I _OF at λ _max1 are clearly pronounced, but are low in absolute values. It could be observed that the course of the curve on other comparable skin areas of the same person or of other people always brought the same result within the scope of the measurement accuracy, and is therefore characteristic of these.

The course of the curve on a dark-colored skin area, which is usually referred to as a birthmark (NaevuszelInaevus), is not shown. It could be observed here that the intensities of both the intrinsic fluorescence I _F and the reflection light I _R _become vanishingly small at the same excitation wavelength λ _A and at the same fluorescence wavelength λ _max1 . The same result was obtained from the examination of the flat part of a skin tumor (melanoma), which is often indistinguishable from the birthmark, even for the trained eye of the doctor.

Surprisingly, however, it was found in these investigations that the intensities of the reflection light I _R at λ _A and the intrinsic fluorescence I in the transition area between normal-colored skin and the tumor, ie in areas in which discoloration is not yet perceptible to the eye _F , also excited with λ _A and measured at λ _max1 , increase considerably. This fact is shown in the upper measurement curve. It can also be seen that I _F increases by at least a power of ten.

The lower diagram in FIG. 4 shows the registered spectrum in the node of the tumor (exophytic part). Here too, the reflection intensity I _{R is} again very pronounced. It is striking, however, that the intrinsic fluorescence I _F no longer occurs at λ _max1 , whereas a new fluorescence _band in the longer-wave region at λ _max2 .

FIG. 5 shows the local dependency of the intensity _values I _F at λ _max1 and λ _max2 , again the tumor already mentioned for FIG. 4 being measured. This is shown in Figure 5 above the measurement curves. It is divided into an outer area 50, the so-called flat part 51 of the melanoma and the so-called knot (52), which often protrudes from the flat part (51) like a tumor.

The upper diagram in Figure 5 shows that the intensity I _F falls in the vicinity of the tumor that is in the still as a "healthy" classified skin region with increasing distance from melanoma back to normal values. The same applies to the reflection intensity I _R. The size of the transition area, ie the distance from melanoma to histologically healthy skin, depends of course on the extent of the tumor. However, it can be measured reliably with the arrangement according to the invention.

The lower diagram in FIG. 5 clearly shows the position of the node (52). The flat part (51) gives no signal in terms of measurement technology.

The decisive importance of the measurement results described so far is that by using the arrangement according to the invention, the beginning of an anomaly in the skin tissue can be reliably determined. Since the characteristic normal reaction of the skin and the anomaly effects always overlap in the initial area, it is important for a safe limitation of the melanoma area that the locally measured intensities correspond to the intensity In normal, healthy skin. Only then can anomalies in the area of apparently normally colored tissue areas be reliably identified.

It is still not possible with the current state of knowledge and technology, at least at the beginning of the anomaly in the skin area, to make a clear decision about the presence of a melanoma. Trial excisions, which very often lead to blemishes in the area of the removed tissue areas, have so far been the only way to carry out a hi-stologic examination and then to be able to make a clear decision about the presence of a melanoma. The non-invasive method disclosed above makes the previously unavoidable sample excision superfluous, since in in-situ measurements allow a clear distinction to be made about the malignancy of the examined skin area. In addition, in the case of melanoma, she can show the surgeon the extent of the degenerated skin area and give him an indication of the size of the pathological skin area to be removed.

Claims

Claims:

1. Arrangement for measuring a condition value for organic tissue areas with

A projection device for projecting a slit image onto the tissue surface,

A measuring device for measuring the backscattered light,

- An evaluation device for analyzing the backscattered light and

- A display device for the measured values, wherein according to patent application P 35 42 167.3

The projection device contains means for generating a monochromatic excitation beam with the wavelength λ _A ,

The measuring device contains a registering spectrophotometer,

- The evaluation device the wavelength λ assigned to a maximum intensity I of the registered backscatter spectrum

_{ma x} , contains a memory with a state value scale, which is assigned an empirically determined table of values for the measurement parameters λ _A , λ _{ma x} , I and the inten tity conditions derived therefrom, and the sought state value of the organic tissue area determined by comparing the current measurement parameters with the table of values in the memory, characterized in that a) the excitation wave length λ _{A is} between 320 nm and 550 nm, b) the spectrophotometer records the backscattered light in the wavelength range between 320 nm and 700 nm and c) the evaluation device determines the maximum intensity of the reflected light at the wavelength λ _A and the maximum intensity of the fluorescent light in the region which is boring to λ _A.

2. Arrangement according to claim 1, characterized in that the Projection device and the detector part of the measuring device are combined to form a separately mounted measuring head and a separate device is provided for supporting the tissue surface, the measuring head and the tissue surface being displaceable relative to one another in a defined manner.

3. Arrangement according to claim 1, characterized in that the projection and / or measuring device is assigned a video camera with a downstream monitor for positioning the slit image on the tissue surface.

4. Arrangement according to claim 2 or 3, characterized by a measuring device for the distance between different measuring positions of the measuring head relative to the tissue surface.

5. Arrangement according to one of claims 2 to 4, characterized by a motor drive for relative displacement and a signal generator for controlling the motor drive and calling the measurement parameters determined in predetermined measurement positions.

6. Arrangement according to one of the preceding claims, characterized in that the memory of the evaluation device contains at least one empirically determined parameter set λ _A , I _o1 , λ _{ma x1} as a reference and the current measured values I ₁ at λ _A , λ _{ma x1} for normalization I _o1 can be obtained.

7. Arrangement according to claim 6, characterized in that at least one reference parameter set is provided for each excitation wavelength λ _A.

8. Arrangement according to claim 6 or 7, characterized in that for at least one excitation wavelength λ _A at least one further reference parameter set I _o2 , λ _max2 for

Normalization of the current measured values I ₂ at λ _A , λ _{ma x2 is} provided.

9. Arrangement according to one of claims 6 to 8, characterized in that for determining the local distribution of the reflection light and / or the fluorescent light, the parameter set serving for standardization is determined in each case in the starting position of the measurement and is entered into the memory.

10. Arrangement according to the preamble of claim 1, characterized in that the evaluation device as a function of a monochromatic excitation wavelength λ _A from the range 320 mm to 550 mm as parameter pairs Maximum I _{F of} the fluorescent light in the range 380 mm to 700 mm and assigned wavelength λ _max umd maximum I _{R of} the reflection light with assigned λ _A determined.

11. The arrangement according to claim 10, characterized in that the evaluation device a comparison of the locally measured value I _F (λ _max ) and I _R (λ _A ) with an empirically determined normal value I _OF (λ _max ) and I _R (λ _A ) at the same excitation wavelength λ _A.