WO2011116878A2

WO2011116878A2 - Spectrometer and examination device having such a spectrometer

Info

Publication number: WO2011116878A2
Application number: PCT/EP2011/001093
Authority: WO
Inventors: Reimund Maier; Frank Zimmermann; Peter Lais; Jutta Eberhart; Sascha Seile; Herbert Gebhardt
Original assignee: DüRR DENTAL AG
Priority date: 2010-03-23
Filing date: 2011-03-05
Publication date: 2011-09-29
Also published as: DE102010012301A1; WO2011116878A3

Abstract

An examination device for optically examining tissue areas (10) in body cavities comprises light-emitting diodes (24), by means of which the examination area (26) can be illuminated with light of different wavelengths as selected. Sample light returning from the examination area (26) reaches an image converter (40) by means of an objective (36) and a multi-filter (58), which comprises a plurality of strip-shaped interference filters. By producing a relative motion between the multi-filter (58) and the image converter (40), fluorescence images of the examination area (26) can be determined for predefined spectral ranges. Diseased tissue areas can be differentiated from healthy tissue areas by comparing and/or linking the spectral sub-images.

Description

Spectrometer and examination device

with such

The invention relates to a spectrometer according to the preamble of claim 1 and to an examination apparatus having such according to the preamble of claim 9.

The early diagnosis of cancer is an important area of medical and dental diagnostics.

For early detection, on the one hand, cell material of tissue areas to be checked is removed for further examination, which can be done in the case of mucous membranes such as the oral mucosa by means of a swab made with a more or less hard brush. Alternatively, small tissue samples can be obtained with a scalpel or similar device.

These methods are slow because the removed cells must be examined in a laboratory. These methods are also uncomfortable for the patient.

It has already been proposed to differentiate healthy and diseased tissue lines by their fluorescence spectrum.

For example, dental handpiece cameras are already known on the market, which illuminate the tissue surface with UV light and examine the fluorescence emitted by the tissue regions. Such a camera is described in WO 2005/110206 A.

This document also suggests a distinction between diseased and healthy tissue by comparing different spectral components of the fluorescent light returning from the examination area. It has also been recognized that by using different design light, one can provide an additional parameter that allows discrimination of diseased and healthy tissue.

In the known diagnostic camera but only a very rough distinction spectral components is possible.

The present invention is intended to open up the possibility, by using a compact device, to achieve a finer separation of light (sample light) thrown back from a sample into spectral components.

For this purpose, the invention provides a spectrometer with the features specified in claim 1 and an examination device according to claim 9.

In the spectrometer according to the invention, the separating means splitting the sample light into spectral components is a multifilter which comprises a closely adjacent arrangement of bandpass filters. In this way, you can accommodate a large number of filters in a compact volume.

Such multifilters can be hertstellen as interference filter by vapor deposition of a permeable to all portions of the sample light substrate with dielectric or metallic layers, which differ in material and / or in thickness. Such evaporations can be precisely and well reproduced with the methods known from the vapor deposition of semiconductor elements. - 3 -

make bar.

Such a multifilter can be designed pixel-like with small filter surfaces or have strip-shaped filter surfaces.

The filter surfaces can be adapted in their geometry to the geometry of the pixel arrangement of an image converter.

A fringe filter has the further advantage that it is well adapted to the geometry of conventional imagers in which individual detection elements (pixels) are arranged in matrix form. Such image converter thus receives closely adjacent arranged in lines detection elements that can form a spectrometer combined with a strip filter. This spectrometer consists of a multiplicity of detection elements with filters arranged in each case in front of a detection element or a group of detection elements, each of which transmits a narrow wavelength range.

In principle, a separate associated filter element of a multifilter designed as a matrix can be formed for each pixel of the image converter. In this case, first the substrate of the filter is provided with a thick coating which is suitable for the longest wavelength to be detected. In the case of the filter pixels corresponding to the other pixels of the image converter, this layer is reduced by controlled removal in such a way that in the end each pixel of the filter corresponds to a different narrow transmission wave range.

According to claim 3, the individual filter areas of the multifilter strip-shaped and fit so well to Geome- trie the arranged in lines detector elements of an imager. Where it matters, the spectral

To determine distribution of sample light, you can then superimpose the output signals of the detector elements

and thus improve the signal-to-noise ratio.

The development of the invention according to claim 4 makes it possible to produce the ultifilter with cheaper methods. The spectral resolution is then of course reduced, but is sufficient for many applications, in particular

for a first rough overview of tissue areas. In addition, the possible combination of several detector element lines into an image line (internal) results in an improvement of the signal / noise ratio.

In a spectrometer according to claim 5, the full area of the imager is simultaneously exposed to sample light. The development of the invention according to claim 7 makes it possible for each line of an image, the spectral

Determine the distribution of the sample light. By

For each image line (and therefore for each pixel), the spectral distribution of the sample light is obtained for each image line (and thus for each pixel). From the data obtained in this way it is then possible to obtain a picture of the image for each examination wavelength of the strip filter

Create an examination area in the corresponding color.

With the development of the invention according to claim 6 it is achieved that sample light from an examination area in which the extraction of an image is not necessary, is decomposed into its spectral components, for which no complicated mechanics is necessary. A Deflection unit, which guides the sample light over the strip filter and the image converter, can be easily formed by a revolving mirror, a revolving prism or a circumferential plane-parallel plate.

The development of the invention according to claim 8 makes it possible, the various output from the image converter signals corresponding to image lines, in each case for a

Store color designated storage areas.

The development of the invention according to claim 10 allows the determination of the spectral components of returning from the examination area sample light upon excitation of the examination area with different wavelengths wavelengths.

According to the development according to claim 10, the different wavelengths can be realized in a very compact multi-wavelength excitation light source.

According to the development according to claim 11, one can filter out the different excitation wavelengths from the sample light, which improves the quality of the fluorescent light images. In this case, you can apply a mechanism that provides the various barrier filter in the beam path with the control commands for the multi-wave light source and thus ensure that for each of the wavelengths each time the right barrier filter is placed in the beam path.

Alternatively, one can according to claim 12 in the way of

Sample light a high-pass edge filter whose edge is slightly above the longest wavelength, which is emitted by the multi-wavelength light source. These Arrangement is characterized by a particularly simple structure and is sufficient for many practical applications, when fluorescence spectrum and excitation spectrum are clearly spaced, so that the high-pass edge filter does not retain fluorescent light, which at

Irradiation of the examination area with short-wave portions of the multi-wave light source is obtained.

Fluorescence, which in tissues by short-wave

Stimulus is relatively weak.

It is therefore advantageous if the examination device can be left to work for a longer time at a given examination area in order to produce a low-noise image by temporally integrating the image signals. For this purpose, one obtains with the development of the invention according to claim 13, a position stabilization of the examination device in the tissue area to be examined.

In a body cavity, tissue areas are often to be examined, which have different orientation to an opening, through which an examination device can be introduced into the body cavity. With a device according to

Claim 14 can be an examination head ^', which contains the mechanical, optical and electronic Hauptento- nenteh angularly different from one

Align the grip section of the examination device, which allows a better ergonomic handling of the examination device. Also, the development of the invention according to claim

15 is used, the examination device at substantially the same orientation of the handle portion for the study of differently oriented tissue areas

to be able to use. The development of the invention according to claim 16 is in view of the improvement of the signal / noise ratio of advantage.

An examination device according to claim 17 makes it possible if necessary to deliver the image of an examination area, as would be the case if observed with a normal white-light camera. The invention will be explained in more detail by means of embodiments with reference to the drawing in which:

FIG. 1 shows an axial section through an examination head of a medical or dental examination device for the early detection of cancer;

Figure 2 is a schematic representation of the adjustment mechanism of a strip grid, which is used in the examination head according to Figure 1;

Figure 3: a schematic plan view of a section of the strip grid of Figure 2 and a

Section of an image converter, which is arranged behind the strip grid, in enlarged

Scale;

FIG. 4: an end view of the one shown in FIG

Examination head (there from the left);

FIG. 5 shows a schematic block diagram of the electronic components of the examination head according to FIG. 1; FIG. 6: a schematic side view of a sub-frame Suchungskopfes, which has a hinge with

a handle portion is connected;

FIG. 7 shows a plan view of the arrangement shown in FIG. 6; and

FIG. 8 shows a schematic representation of a spectrometer which comprises an image converter, a strip grid and a beam deflection unit.

In FIG. 1, 10 denotes a tissue region,

which may be part of the oral mucosa of a patient. The tissue region has a surface 12 onto which an examination head, generally designated 14

is attached.

This has a generally designated 16 housing with a cylindrical peripheral wall 18, a circular disc-shaped rear bottom wall 20 and a cylindrical end portion 22, which is made of transparent plastic material and is tightly inserted into the peripheral wall 18.

In the front part 22 are light-emitting diodes 24-1 to 24-8

inserted (cemented or cast in) whose beam axes are aligned so that they are the center of a

Investigation area 26 meet. The light-emitting diodes

24 each have such large opening angle that one

Pair of diametrically opposite LEDs the examination area 26 completely and preferably uniformly lit (possibly using a lens). In each case a pair of diametrically opposite LEDs 24 emits light with the same spectral distribution. The emission wavelengths of the different pairs of light emitting diodes are different. For example, diodes 24-1 and 24-5 may be white light diodes while diodes 24-2 and 24-4 output 260 nm light, and light emitting diodes 24-4 and 24-8 emit 340-350 nm light.

Alternatively, diodes may be used which radiate in the ranges 405 to 414 nm, 540 nm, 578 nm and near infrared. In this case, either the number of pairs of diodes is increased accordingly, or only one will be available for each wavelength range

LED provided.

In particular, with the different wavelengths given above, fluorescences of the following molecules can be excited: nicotinamide adenine dinucleotide [NAD (H)], flavin adenine dinucleotide [FAD (H)], porphyrins (e.g.

Hemoglobin). The examination head 14 has a central through-bore 28, in which a first lens 30 is seated. Escaping with this two more lenses 32, 34 are provided. The three lenses together form an objective 36. Between the lens 32 and the lens 34 there is provided a (wavelength-wise) high-pass edge filter 38 whose edge is laid so that the excitation light of the longest wavelength (in this case 350 nm) is just reliably retained.

An imager 40, which may be a known CCD component, is mounted on a carriage 42, which in turn is slidable on guide rods 44 carried by retaining eyes 46 fixedly connected to the peripheral wall 18 of the housing 16. about a threaded spindle 48, which is driven by a stepping motor 50, the carriage 42 and thus the image converter 40 along the axis of the lens 36 are moved to focus the image of the examination area 26 on the image converter 40. The current position of the stepping motor 50 can be replaced by a

Positioner 52 is coupled, which is coupled to the stepper motor 50. The top of the carriage 42 also carries two guide rails 54, 56 in which a strip filter 58 is guided.

The strip filter 58 is adjustable by a linear motor 60 perpendicular to the plane of Figure 1.

The position of the strip filter 58 is replaced by a

Positioner 62 controls that cooperates with the linear motor 60. FIG. 2 shows the image converter 40 located behind the strip filter 58 in dashed lines. It can be seen that the strip filter 58 has a dimension, seen in the direction of movement, which is slightly larger than twice the dimension of the image converter 40 in the same direction.

The stripe filter 58 has two regions 58A and 58B which abut seamlessly and are each slightly larger than the window of the imager 40. In Figure 2, the memory filter region 58B is graphically raised against the memory filter region 58A by a punch. Physically, the two memory filter areas

but similar.

As can be seen in FIG. 3, they each comprise a succession of filter strips 64-i (i = 1,2,3, ... J). Each of these filter strips represents an interference filter for a wavelength range.

The imager 40 has pixel columns 65-j (j = 1,2 ..., M), and pixel rows 66-k (k = 1, 2, ..., N). Where M is the number of columns, N is the number of lines of the image converter 40, J is the number of wavelength ranges,

which are to be spectrally resolved. Pixels of the imager 40 are labeled 68 (, k).

The number of resolvable wavelength ranges is at a strip filter, as it is considered here, a maximum of M, ie the number of columns of the image converter 40. For practical reasons (manufacturability of the strip filter with available Bedampfungsapperaturen) keeping the number of filter strips but significantly smaller as the number of columns of the image converter. If, for example, one wishes in the range between 400 and 800 nm

Resolution of the spectrum in steps of 50 nm, so eight different filter strips must be provided.

With a size of the transducer chip of 12 x 8 mm, this means a width of the individual filter strip 64-i of 1.5 mm. For a 640 x 480 pixel imager, this means that a filter strip has 38 image splitter gaps

concealed at the same time.

In order to keep the examination head 14 immovably above the examination area 26, eight circular sector-shaped shallow recesses 70 are formed in the end face of the front part 22. These each depend on one

Suction channel 72 on a vacuum line 74. In the suction channels 72 small throttles 76 are each provided, which limit the suction flow. If the examination head 14 on the tissue surface put on, so builds up in the recesses 70

Vacuum, which holds the examination head 14 immovably above the examination area 26. It is sufficient if some of the wells 70 vacuum-tight

sit on the fabric.

Through the bottom wall 26, 74 supply lines 78 are performed for each of the light emitting diode pairs in addition to the vacuum line. Lines 80, 82 are used for supply

the stepper motor 50 and the linear motor 82, and other lines 84, 86 output signals of the position sensors 52 and 62. A line 87 provides the output signals of the image converter 40. FIG. 5 shows the electronic part of the examination head, which is located in an external operating unit, partly also can be integrated into a handle which carries the examination body 14. At 88, a processor is shown which may be a programmable computer with appropriate interfaces

can. The processor 88 receives via the line 87 the image signals provided by the image converter 20, via the line 84 of the output signal of the position sensor 50 and via the line 86, the output signal of the position sensor 62. The processor 88 is a screen

90 and a keypad 92 to control the processor and input parameters for image processing. Images of the examination area created by the processor 88 can be displayed both on the screen 90

as well as on a printer 94.

In FIG. 5, various memory areas 96-1 to

96-J shown externally for illustrative purposes. she

may in fact be due to areas of memory be formed of the computer. The number of memory areas corresponds to the number of different filter strips

which are provided on the strip filter area 58A and 58B, respectively.

The examination device described above works like

follows:

The examination head 14 is placed on a point to be examined of the tissue area 10, wherein the

Vacuum line 74 is already subjected to vacuum.

The examination head 14 now sucks at the examination site. Controlled by the processor 88, the first UV light source is formed, which is formed by the light-emitting diodes 24-2 and 24-4 and radiates at 260 nm.

In a starting position of the strip filter 58, which corresponds to the position of Figure 2, a first

Image of the sub-area recorded. This image comprises eight image strips each in the color of the filter strip in front of them. The processor 88 now reads out the content of the image converter 40 in the usual way and stores this image in strips

an associated memory 96-. After this first readout of a picture is thus found in each of the

Memory 96-j is a partial image of the examination area.

These image strips juxtaposed would give an image of the entire examination area, but each image strip would have a different color.

The linear motor 60 is then controlled by the processor 88 in such a way that it displaces the line filter 58 by one strip width. During translation, the imager becomes dead, ah it is reactivated.

The now obtained image of the image converter 40 is again read out as described above, but the image strips now have a different color and in others the

Memory 96-j are stored. Each of the image memories now contains two adjacent image strips of the same color.

The processor 88 then controls the linear motor 60 again so that the strip filter 58 is offset by one strip width. Now you get from the different ones

Image strips images in a third color, which are again stored in the corresponding memory areas 96-j. Each of the image memories 96-j now contains three adjacent image strips of the corresponding color.

The above-described cycles are continued until the filter region 58A is completely moved over the image converter 40. Now arises in each of the

Image memory 96-j a complete image of the examination area in a color corresponding to the memory.

Upon completion of the measurement, when the stripe filter 58 is completely pushed over the imager 40, the processor 88 then begins to evaluate the fields stored in the memories 96-j.

This evaluation can be done in different directions: First, one can subject the subpictures to a picture manipulation by selecting the ones in the various memories

96-j stored images concatenated according to predetermined criteria. In particular, a concatenation may be a flush assembly into an overall image or else a multiplication of the individual pixel intensities Include images of different colors.

One can also see the spectral distribution for the light on a single image pixel from those in the memories

Detect and display 96-j stored data, which gives a histogram representation of the spectrum for each image pixel. These spectra can then be visually evaluated or linked together again.

A concatenation can also include a difference formation and / or a quotient formation.

Yet another type of evaluation would be that, particularly in the case of weak fluorescent light signals, the various images lying in the memories 96-j are converted into a total image or a small number of images

Total images, the latter being the sum over a group of spectral regions. Such a thing

Can eat together for a simple / automated

Evaluation of the results may be beneficial.

If required, a white light image of the examination area can also be produced with the examination device described above. For this purpose, the white light LEDs 24-1 and 24-5 are activated by the processor 88, and the reading of the image converter and the storage of the various image strips is the same as above

described. Thus, 96-j color separations of the white light image in different color ranges are obtained in the memories. To represent a conventional white light image, the sub-images residing in the memories 96-j are then simply added. The cycles described above can then be vation of another set of light-emitting diodes, so as to obtain spectrally decomposed fluorescence images of the examination area, which were obtained under irradiation with light of different wavelengths.

The spectral distribution of light at an image pixel or a range of adjacent image pixels may also be compared in processor 88 to comparable values of a known healthy tissue region (same patient or from a comparison database) to determine if a disease is present and how far, if any has progressed.

Figures 6 and 7 show how the inspection head 14 can be connected to a grip portion 98 which facilitates handling of the inspection head within a body cavity.

The examination head 14 runs cross-sectionally in cross section at its end remote from the objective and a joint plate 100 is pulled out of the lower generating line.

Similarly, the handle portion 98 is tapered at the end facing the inspection head 14 and has a hinge plate 102 pulled out of the lower surface line. The two hinge plates 100, 102 are interconnected by a uniaxial hinge 104. Due to this design of examination head 14 and handle portion 98, it is possible to adjust the examination head 14 inclined to the rear, as shown in dashed lines in Figure 6. In this way, the

The examination head 14 then the front portion of the oral cavity and lying on the inside of the jaw Examine gums. In the place represented by solid lines, the examination head is suitable for examining deeper parts of tissue lying in the oral cavity.

On the front end of the examination head, a deflection unit 106 can be rotatably mounted in order to allow a perpendicular to the axis of the handle portion 98 observation. In the interior of the deflection unit 106, a deflecting mirror 108, which is arranged at 45 ° to the axis of the examination head, is accommodated, which deflects laterally sample light entering through a window 110 onto the axis of the deflection head 14. FIG. 8 shows a compact spectrometer constructed in a simple manner, which comprises an image converter 40 and a strip filter 58 mounted flush thereon. If the strip filter has a number of filter strips 64-i which corresponds to the number of detector lines 66-j of the image converter 40 and if the distance of the filter strips 64 corresponds to that of the pixel columns 66, then the strip filter / image converter unit is irradiated with one

Sample light for each column of the imager a total electrical signal which corresponds to the intensity of the light in the lying before the image column filter strip wavelength range.

If the sample light is not already flat and homogeneous by itself, a narrow light beam 112 can be produced from the sample light using a diaphragm

Hide 114 and guide the light beam 112 over the strip filter 58. This can be done, for example, using a plane-parallel optical baffle 116 that is perpendicular to the plane of the drawing of FIG

Plane is rotated. The position of the light beam at the shown in Figure 8 position of the baffle 116 is shown in Figure 8 by a solid line. Dashed lines show the deflected light beam

112 in the boundary layers, which are obtained when turning the baffle 116.

The spectral resolution of such a spectrometer is limited by the total number of image columns of the transducer. With a converter with 640 x 480 pixels one can thus dissolve maximally 640 wavelength intervals.

The range of visible light can thus be analyzed with a resolution of 1 nm. If you halve the number of light stripes so that each light stripe covers two columns of the light converter, you still have a resolution of 2 nm. If you choose the width of the filter stripes equal to ten times the distance of the image columns, a resolution of 10 nm remains.

Such resolutions are quite comparable to those of prism spectrometers. Here is the resolution

ultimately not dependent on the dimension of the light beam to be analyzed. It is therefore entirely possible to work with larger gaps if it is only ensured that the entire cross section of the light beam is moved over the surface of the strip filter 58. The spectrometer of Figure 8 is thus characterized by a high sensitivity. It also has a very compact and mechanically simple construction. Of course, in the spectrometer of Figure 8

strip filter 58 may comprise only a single set of filter strips 60, for example only strip filter section 58A.

Claims

claims

1. spectrometer, in particular for the investigation of

tissues lying in body cavities, with an excitation light source (24), with photoelectric detection means (40) and separation means (38) arranged between an examination area (26) and the detection means (40), which decompose the sample light returning from the examination area into spectral portions .

characterized in that the decomposition means a

Multifilter (58) having subregions (64) which pass only light of a predetermined wavelength range.

2. Spectrometer according to claim 1, characterized in that the detection means (40) has a regular

Arrangement of detection elements (68), wherein the arrangement is preferably in lines of equidistant detection elements (68) or a plurality of such lines of detection elements.

3. Spectrometer according to claim 1 or 2, characterized in that each of a predetermined wavelength range transmitting portions (64) of the multi-filter (58) are strip-shaped and in their geometry of the shape and arrangement of the detection elements (68) of the detection means ( 40) are adjusted.

4. A spectrometer according to claim 3, characterized in that the detection elements (68) in equidistant

Lines are arranged and each having a predetermined wavelength range transmitting portions (64) of the Multifilters (58) are strip-shaped, wherein preferably the width of the individual filter strips correspond to an integer multiple of the pitch of the lines of the detection means (40).

5. Spectrometer according to one of claims 1 to 4, characterized in that the dimensions of the multifilter (58) are at least equal to the dimensions of the detection means (40).

6. A spectrometer according to claim 5, characterized in that it comprises a deflection unit (116) which guides a sample light bundle (112) over the detection means (40) such that each region of the detection means equally depends on the entire cross section of the sample light bundle (112). is swept over.

7. A spectrometer according to claim 5, characterized in that a dimension of the multifilter (58) is twice as large as the corresponding dimension of the detection means (40) and the multifilter (58) via the detection means (40) is movable.

8. A spectrometer according to claim 7, characterized by

a filter position sensor (62) which measures the relative position between the multifilter (58) and detection means (40) and whose output signal is used to address memory areas (96) into which the output signals of the detection means (40) are read for each incremental change in the relative position become.

9. examination device, in particular for examination

of body tissues, with an excitation light source (24) forming an examination area (26) illuminated, with an optical system (26) for imaging the examination area (26) on an image converter (40) and preferably also in the beam path between the examination area (26) and image converter (40) lying blocking filter arrangement (38), which retains excitation light and for which the sample light returning from the examination region (26) is permeable, characterized in that a multifilter (58) according to one of claims 1 to 8 is arranged in front of the image converter (40).

10. examination device according to claim 9, characterized in that the excitation light source (24) has a

Has a plurality of solid-state light sources (24-i) that emit light of different wavelengths, preferably LEDs.

11. Examination device according to claim 9 or 10, characterized in that the barrier filter arrangement (38) comprises a plurality of optionally adjustable in the beam path blocking filter, which are preferably carried by a flexible substrate.

An examination apparatus according to claim 9 or 10, characterized in that the notch filter arrangement (38) comprises a high pass edge filter whose edge is at the longest wavelength which the excitation source (24) provides.

13. examination device according to one of claims 9 to

12, characterized in that a front end portion of an examination head is provided with at least one suction recess (70) open on one side, preferably with a plurality of such suction recesses (70).

14. examination device according to one of claims 9 to

13, characterized in that an examination head (14) of the device articulated (104) with a handle portion (98) is connected, wherein the adjustment angle is preferably greater than 90 °, more preferably greater than 120 °.

15. examination device according to one of claims 9 to 14, characterized by a about the axis of the optics (36) rotatable deflecting mirror (108).

16. examination device according to one of claims 9 to

15, characterized in that it comprises memory means (96), each containing an image of the examination region (26) in a wavelength strip corresponding to a filter strip (63) and computing means (88) are provided which the spectral in the memory means (96) Combine single images according to given rules.

17. examination device according to one of claims 9 to

16, characterized by a white light source (22-1, 22-7).