WO2011141202A1

WO2011141202A1 - Microscope and method for skin examination

Info

Publication number: WO2011141202A1
Application number: PCT/EP2011/053941
Authority: WO
Inventors: Axel Rumberg; Michael Thiel; Ulrich Kallmann
Original assignee: Robert Bosch Gmbh
Priority date: 2010-05-12
Filing date: 2011-03-16
Publication date: 2011-11-17
Also published as: EP2569666A1; DE102010028913A1

Abstract

A microscope (10) for skin examination by means of THz radiation has a camera (14) operating in the visible spectral range and a Vis imaging optical unit (15) operating in the visible spectral range and serving for imaging a sample (11) onto the camera (14). The microscope (10) furthermore has a THz radiation source (31) for generating THz radiation, a THz camera (32) operating in the THz spectral range, and a THz imaging optical unit (33) operating in the THz spectral range and serving for illuminating the sample (11) with the THz radiation and imaging the sample (11) onto the THz camera (32).

Description

Description title

Microscope and procedure for skin examination

State of the art

The invention is based on a microscope and a method for skin examination. Microscopes for skin examination are known, for example from US 2008239474. Various optical methods for the detection of skin cancer are performed by the doctor and have according to the equipment cost certainty in the range 60% to 98%. The use of THz radiation to detect skin cancer is also known. In the frequency range 0.1 -5 THz, changes in the refractive index and the absorption behavior in the skin can be analyzed by reflection measurements, whereby healthy skin cells and cancer cells have a different

Water content and therefore a different refractive index and a

have different absorption behavior. The expected difference between healthy and cancerous skin is approximately 10%. The frequency determines the optical resolution and penetration depth. Low frequencies around 200 GHz have a resolution of 2.5 mm. Higher frequencies can dissolve finer, but have a lower penetration depth and require more effort in the generation. US 2008/0319321 discloses an imaging study using THz radiation wherein the THz radiation is generated by means of femtosecond pulses of a mode-locked titanium-sapphire laser in a dipole antenna. The reflected THz radiation from a sample is also converted in a dipole antenna into an electrical signal, which is then analyzed. This radiation generation and the radiation detection require a lot of effort. Are now

less expensive THz radiation sources available. The THz image is difficult to compare with the image in the optical spectral range. Disclosure of the invention

In contrast, the microscope and the skin examination method according to the present invention have the advantage of enabling a simple and inexpensive skin cancer screening or skin cancer examination. The microscope can be designed as a patient device that allows close observation of nevi and additionally evaluates the naevi examined based on an analysis of the water content. By a relative measurement, the method works independently of the absolute skin moisture. The detection of skin moisture is done with the help of THz radiation. The skin area to be examined is illuminated with THz radiation and with visual radiation. The reflected THz radiation and visual radiation is detected, evaluated and displayed in a superimposed image. Basically, skin areas are considered that consist of normal (healthy) skin and potentially diseased skin. A colored display enlarges the examined area and possible differences in skin hydration are shown by an additional discoloration.

Brief description of the drawings

Embodiments of the invention will be explained with reference to the drawings, in which

Fig. 1 shows a schematic representation of the microscope according to an embodiment of the present invention;

Fig. 2 is a schematic representation of the microscope according to another

Embodiment of the present invention shows; and

3 is a flowchart of the method according to an embodiment of the present invention

Invention shows.

Embodiments of the invention

1 shows the microscope 10 for skin examination by means of THz radiation according to an embodiment of the present invention as a reflected-light microscope and a skin sample 11 to be examined. The microscope 10 has a visual beam path 12 in the visible spectral range, between a light source 13 and the

Skin sample 1 1 and between the skin sample 1 1 and a working in the visible spectral range camera 14 with a visible CMOS detector runs. In the optical

Beam path 12 is by means of working in the visible spectral range Vis imaging optics 15 on the one hand the light source 13 on the sample 1 1 and on the other hand, the sample 1 1 imaged on the camera 14, more precisely to a sensor in the camera 14. The vis-imaging optics 15th consists of the lenses 16, 17 and the beam splitters 18 and 19. The visual useful radiation extends according to the arrows 20, 21, 22 and 23. In this case, a visual Vis transmission radiation from the approximately point-shaped light source 13, is through the beam splitter 18 and 19 deflected, parallelized by means of the lens 16, and focused by means of the lens 17 on the skin sample 1 1 and there illuminates an illuminated area 24. From the skin sample 1 1 now goes out a visual Vis-receiving radiation is parallelized by the lens 17, and the focused by means of the lens 16 on the camera 14 and thereby deflected by the beam splitter 19. The Vis reception radiation from a detection area 25 is detected by the camera 14. The illuminated area 24 and the detection area 25 are through

Adjustment brought to coincidence.

The microscope 10 has a THz beam path 30 in the THz spectral range, which is between a THz radiation source 31 and the skin sample 1 1 and between the

Skin sample 1 1 and operating in the THz spectral THz camera 32 runs. In the THz beam path 30, on the one hand, the THz radiation source 31 is imaged onto the sample 11 by means of a THz imaging optical system operating in the THz spectral range and, on the other hand, the sample 1 1 is imaged onto the THz camera 32, more precisely to a sensor in the FIG THz camera 32, a CMOS array, which is in the range of THz

Radiation is sensitive. The THz imaging optics 33 consists of the lenses 34, 35, and 36 and the beam splitter 37. The useful THz radiation proceeds according to the arrows 38, 39 and 40. In this case, a THz transmission radiation emanates from the approximately point-shaped THz radiation source 31, is parallelized by means of the lens 34, deflected by the beam splitter 37, focused by means of the lens 35 on the skin sample 1 1 and there illuminates a THz-illuminated area 41st From the skin sample 1 1 is now a THz received radiation from, is parallelized by means of the lens 35, and focused by means of the lens 36 on the THz camera 32. The THz reception radiation from a THz detection area 45 is detected by the THz camera 32. The THz-illuminated region 41 and the THz detection region 45 are aligned by adjustment. Also, an adjustment must ensure that the visual image and the THz image are aligned with each other. For this purpose, the visual image is brought into coincidence with the THz image, preferably by adjusting the beam splitter 19 with a suitable adjustment sample. The central image pixel of the visual and the THz image now corresponds in each case to the same small object surface of the sample, so that a superimposed image can be generated from both.

The microscope 10 further has a control and evaluation unit 42 and a monitor 43 as an output unit 44. The control and evaluation unit 42 is connected to the light source 13, the camera 14, the THz radiation source 31, the THz camera 32 and the monitor 43.

The THz radiation source 31 in FIG. 1 is a quantum cascade laser. Suitable alternative THz radiation sources are also an oscillator-mixer frequency multiplier combination or a backward wave oscillator.

The THz camera 32 has here a CMOS array, which is sensitive in the range of THz radiation. The THz camera can basically be realized by different detector systems. For a good spatial resolution, it must be ensured that an image pixel corresponds to a small object surface

Detector pixel at a time so only receives radiation from this small object surface. The two-dimensional THz image of the sample can be obtained with a point detector by two-dimensional scanning, with a line detector by one-dimensional scanning, or with a two-dimensional detector without scanning. Scanning can be done by moving the sample or through more elegant

Moving the detector or the beam source or deflecting the receiving beam or the transmission beam can be achieved. Advantageously, the deflection, since only small masses are moved. Different variants are now presented. So the THz camera can use a point detector and the microscope

have two-dimensional scanning mechanism. In this case, in a first variant with point-shaped THz illumination of the object, the object is moved. According to a second variant, the beam splitter 37 and the point detector are moved in two axes for the two-dimensional scanning of a stationary sample; at a

line-shaped THz illumination of the beam splitter 37 is moved in only one axis. According to a third variant, the object is illuminated areally with sufficient THz power and the point detector is moved.

According to further variants, the THz camera has a line array detector and the microscope has a one-dimensional scanning mechanism. In planar illumination, according to a fourth variant, the line array is displaceable in one direction or uniaxially displaceable according to a fifth variant of the beam splitter 37. In a sixth variant, an oscillator-mixer-frequency multiplier combination is used as a THz radiation source. Such oscillators can be built either discretely or inexpensively integrated in CMOS technology.

Another variant used as a detector system for the THz camera

Two-dimensional detector array, a Focal Plane Array with planar illumination, as already developed on CMOS basis. This variant has the advantage that no scanning is required or parts of the beam path need not be movable.

The illustrated in Fig. 1 embodiment of the microscope according to the invention as incident light microscope has a common visual and THz beam path portion 46 on the sample. The THz imaging optics 33 and the Vis imaging optics 15 form a common imaging optics 47 with elements operating simultaneously in the visible and THz spectral range. This has the advantage that the images taken by the visual and THz cameras are taken from the same perspective and both are illuminated perpendicular to the sample surface. This facilitates the observation and the adjustment, because the images can be easily superimposed. The optical lenses 16, 17 and the THz lenses 36, 35 are in the

common beam path portion 46 and the lenses 16, 36 and 17, 35 are each identical to lenses 48 and 49. The lenses are made of a material having an approximately the same refractive index in the optical and THz frequency range, in particular polymers such as polymethylpentenes (TPX) and Cyclo-olefin polymer (COP).

The two beam splitters 19 and 37 have different properties. The task of the beam splitter 19 is the reflection of optical radiation and the transmission of THz radiation. The beam splitter 19 is made of uncoated quartz glass, in question is still the material silicon, which is not optically transparent. The task of the beam splitter 37 is the coupling of THz radiation to the common visual and THz beam path section 46, ie the transmission of optical radiation and the Reflection of THz radiation. The beam splitter 37 consists of uncoated quartz glass. An alternative material of the beam splitter 37 are polymers such as TPX, COP.

FIG. 2 shows the microscope 60 for skin examination by means of THz radiation according to a further embodiment of the present invention as a reflected-light microscope and a skin sample 11 to be examined, the parts already known from the microscope 10 shown in FIG. 1 having the parts described in FIG 1 have reference numerals used. The essential difference from the microscope 10 of FIG. 1 is that the positions of the optical camera and the THz camera have been exchanged, and beam splitters and the coupling of the light source into the beam path have been adapted to this geometry. The microscope 60 has a visual beam path 61 in FIG

visible spectral range, which extends between a light source 62 and the skin sample 1 1 and between the skin sample 1 1 and a working in the visible spectral range camera 63. The task of the beam splitter 64 is the transmission of optical radiation and the reflection of THz radiation. The beam splitter 64 now couples THz radiation sideways out to the THz camera 65. The beam splitter 64 is made of quartz glass and is on the side facing the sample coated with a transparent

Conducting oxides (TCO), in particular indium tin oxide (ITO) or zinc oxide (ZnO), with high reflectivity in the THz range and high transparency in the optical spectral range. In this way, the THz beam is approximately completely reflected at the beam splitter 64 and the visual beam is transmitted almost completely, and thus THz radiation and visual radiation are separated from one another. The beam path from the light source 62 now passes over the beam splitter 66, which is an optical beam splitter with 50% transmission and 50% reflection. The optical beam now passes the beam splitter 64 in both directions according to arrow 67 without deflection, from the light source to the sample 1 1 and from the sample 1 1 to the optical camera 63rd

The person skilled in the art recognizes that a common visual and THz beam path can be designed in different ways. With the described beam splitters of the microscopes 10 and 60, visual or THz radiation can be coupled in or out. If the THz camera is designed as a point or line detector, the scan mechanism described above must be adapted accordingly. Likewise, the

Professional instead of the lenses reflection optics, such as aluminum concave mirror, use, the beam path is to be designed accordingly, however, assumes a complicated geometric shape. Likewise, illumination and observation of the sample can take place under separate solid angles or the visual and the THz- Beam path be spatially separated. These spatial separations facilitate the material selection of the beam splitter without the benefits of incident light microscopy.

The illumination in the optical spectral range is shown by way of example in FIG. 1 and FIG. 2 by means of light source 13, but can be realized in many other ways, for example at other positions of the light source with appropriate positioning and selection of the beam splitters or as LED ring around lens 17th

Fig. 3 describes in flow chart 50 a method according to the invention for

Skin examination by irradiation of a sample with transmission THz radiation and

Evaluation of a received from the sample receiving THz radiation with the

Steps:

a) illuminating a sample with transmission THz radiation;

b) illuminating a sample with visual transmission Vis radiation;

c) acquiring a THz image of the sample by means of a receive THz radiation;

d) acquiring a Vis image of the sample by means of Vis-receiving radiation;

e) generating a superimposed image from the THz image and the vis image;

f) displaying the THz image, Vis image and / or the superimposed image. The

Process step pairs a) and b) and c) and d) can each be in any

Order or simultaneously. The method is controlled by the control unit 42, which also generates the overlaid image and displays it on the monitor 43.

The procedure is preceded by a calibration at a reference skin site, against whose reference skin moisture deviations of the skin samples are determined. In the THz

Range is the reflection of the transmitted THz radiation depending on the water content of the skin, which is increased in melanoma compared to healthy skin. In order to be able to make a comparison, a healthy reference skin site and a skin sample to be examined must always be irradiated.

The skin moisture of the sample is determined by the method compared to the skin moisture of the reference skin site from the received THz radiation and in the

superimposed image displayed. Deviations from the skin moisture of the reference skin area are superimposed with false colors on the visual image. The microscope is also suitable for other investigations of skin moisture and examinations of birthmarks. The microscope and the method are used in the frequency range 0.1 -5 THz. Both direct detection and dark field and phase contrast microscopy can be used. In the latter two methods are further apertures and phase plates in

Beam path needed. Both images, the THz image as well as the image in the visible frequency range, are displayed on a display, either separately or as an overlay. From both image information data can then be used for a diagnosis.

Claims

claims

1 . Microscope for skin examination with one in the visible spectral range

working camera (14, 63) and operating in the visible spectral range Vis imaging optics (15) for imaging a sample (1 1) on the camera (14, 63), characterized in that the microscope (10, 60) further has a THz - Radiation source (31) for generating THz radiation, operating in the THz spectral THz camera (32, 65) and operating in the THz spectral THz imaging optics (33) for illuminating the sample (1 1) with the THz - Radiation and imaging of the sample (1 1) on the THz camera (32).

2. A microscope according to claim 1, characterized in that the THz radiation source (31) comprises a quantum cascade laser, an oscillator mixer combination or a backward wave oscillator.

3. A microscope according to claim 1 or 2, characterized in that the THz imaging optics (33) and the Vis imaging optics (15) have a common

Imaging optical system (47) with simultaneously working in the visible and THz spectral range elements (19, 37, 48, 49, 64).

4. A microscope according to claim 3, characterized in that the common imaging optics (47) lenses (48, 49) of polymethylpentenes (TPX) or cyclo-olefin polymer (COP).

5. Microscope according to one of the preceding claims, characterized in that the microscope (10, 60) above the sample (1 1) has a common visual and THz beam path portion (46).

6. A microscope according to claim 5, characterized in that the microscope (10, 60) has a beam splitter (64) for separating or merging THz radiation and visual radiation from or into the common visual and THz beam path section (46). Microscope according to claim 6, characterized in that the beam splitter (64) for separating or merging THz radiation and visual radiation of quartz glass with a coating of a Transparent Conducting Oxide (TCO), in particular indium tin oxide (ITO) or zinc oxide (ZnO) exists.

Microscope according to claim 5, characterized in that the microscope (10) comprises a beam splitter (37) for THz radiation.

Microscope according to claim 8, characterized in that the beam splitter (37) for THz radiation consists of quartz glass.

Microscope according to one of the preceding claims, characterized in that the microscope (10, 60) a light source (13, 62) and another

Beam splitter (18, 66) for illuminating the sample (1 1) with visible radiation.

Microscope according to one of the preceding claims, characterized in that the THz camera (32, 65) has a point detector and the microscope (10, 60) has a two-dimensional scanning mechanism.

Microscope according to one of claims 1 to 10, characterized in that the THz camera (32, 65) has a line array detector and the microscope has a one-dimensional scanning mechanism.

Microscope according to one of claims 1 to 10, characterized in that the THz camera (32, 65) has a two-dimensional detector array.

Method for skin examination by means of irradiation of a sample with transmitted THz radiation and evaluation of a received THz radiation originating from the sample with the method steps;

a) illuminating a sample with transmission THz radiation;

b) illuminating a sample with visual transmission Vis radiation;

c) acquiring a THz image of the sample by means of a receive THz radiation; d) acquiring a Vis image of the sample by means of Vis-receiving radiation; e) generating a superimposed image from the THz image and the vis image; f) displaying the THz image, Vis image and / or the superimposed image.

15. The method according to claim 14, characterized in that a skin moisture is determined from the received THz radiation and displayed in the superimposed image.