DE4015988A1 - IR tomograph based on confocal imaging principal - uses either IR radiation source for computer tomography or IR radiation from cells in biological tissue - Google Patents

IR tomograph based on confocal imaging principal - uses either IR radiation source for computer tomography or IR radiation from cells in biological tissue

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Publication number
DE4015988A1
DE4015988A1 DE4015988A DE4015988A DE4015988A1 DE 4015988 A1 DE4015988 A1 DE 4015988A1 DE 4015988 A DE4015988 A DE 4015988A DE 4015988 A DE4015988 A DE 4015988A DE 4015988 A1 DE4015988 A1 DE 4015988A1
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Germany
Prior art keywords
radiation
biological tissue
cells
computer tomography
confocal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
DE4015988A
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German (de)
Inventor
Hans-Ulrich Dr Dodt
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Original Assignee
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
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Application filed by Max Planck Gesellschaft zur Foerderung der Wissenschaften eV filed Critical Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Priority to DE4015988A priority Critical patent/DE4015988A1/en
Publication of DE4015988A1 publication Critical patent/DE4015988A1/en
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0036—Scanning details, e.g. scanning stages
    • G02B21/0044—Scanning details, e.g. scanning stages moving apertures, e.g. Nipkow disks, rotating lens arrays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0068—Confocal scanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • G01N21/763—Bioluminescence
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0028—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders specially adapted for specific applications, e.g. for endoscopes, ophthalmoscopes, attachments to conventional microscopes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light

Abstract

The optical system uses i.r. radiation as visible light for penetrating biological tissue. The principle of confocal microscopy is used to eliminate dispersed radiation. Two configuration of the system are offered. In the first, the tissue is irradiated from an i.r. source. This can be used for human diagnosies. In the second the i.r. radiation from the cells themselves is made visible, similar to bio-luminescence. Biochemical reactions can be spatically represented on the basis of their specific i.v. emission. This is made possible by recent developments in i.r. CCD's based on silicon doped with platinum. USE - Making deep internal structures in biological tissue visible.

Description

1. Die Erfindung betrifft ein optisches System, daß es ermöglicht Strukturen z. B. im menschlichen Körper ohne jegliche Strahlenbelastung darzustellen. Es nutzt hierbei die Eigenschaft von Infrarotstrahlung aus, im Gegensatz zu sichtbarem Licht erhebliche Gewebedicken durchdringen zu können. So war zum Beispiel gezeigt worden, daß es möglich ist, transkraniell mit einem empfindlichen Photomultiplier noch nahes Infrarot zu detektieren. Auftretende Streustrahlung kann durch Ausnützung des Prinzips der konfokalen Mikroskopie eleminiert werden: Bei der konfokalen Mikroskopie wird durch sehr enge Blenden in den Zwischenbildebenen von Kondensor und Objektiv die Streustrahlung von lateral oder axial außerhalb des Fokus liegenden Strukturen eleminiert. Diese Blenden müssen nun genau parallel über das gesamte Bildfeld gescannt werde. Um dies zu erreichen, sollen in dem vor geschlagenen System zwei axial verbundene Nipkowscheiben verwendet werden (Zeichnung 1a). Um die Lichtausbeute zu erhöhen, können die in archimedischen Spiralen angeordneten Löcher der Nipkowscheibe durch spiral förmige Längsschlitze ersetzt werden (Zeichnung 1b). Dies ist möglich, da aus der konfokalen Mikroskopie bekannt ist, daß mit geringen Auflösungsverlusten Loch- durch Schlitzblenden ersetzt werden können. Da Kondensor und Objektiv große Arbeitsabstände besitzen müssen, sollen Spiegelobjektive verwendet werden. Mit dem beschriebenen Gerät sollte es möglich sein, ohne Strahlenbelastung Vorsorgeuntersuchungen durchzuführen. Da bekannt ist, daß einige tumoröse Gewebe andere Absorptionseigenschaften für nahes Infrarot besitzen, als das Normalgewebe, dürfte durch geeignete Wahl der Wellenlänge auch noch eine gewisse Differenzierung der pathologischen Veränderungen möglich sein.1. The invention relates to an optical system that it allows structures such. B. in the human body without any radiation exposure. It uses the property of infrared radiation, in contrast to visible light, to be able to penetrate considerable tissue thicknesses. For example, it had been shown that it is possible to detect near infrared transcranially with a sensitive photomultiplier. Scattered radiation that occurs can be eliminated by utilizing the principle of confocal microscopy: In confocal microscopy, very narrow apertures in the intermediate image planes of the condenser and objective eliminate the scattered radiation from structures lying laterally or axially out of focus. These diaphragms must now be scanned exactly in parallel across the entire image field. To achieve this, two axially connected Nipkow disks should be used in the proposed system (Figure 1 a). In order to increase the luminous efficacy, the holes of the Nipkow disc arranged in Archimedean spirals can be replaced by spiral-shaped longitudinal slots (drawing 1 b). This is possible because it is known from confocal microscopy that slit diaphragms can be replaced with low resolution losses. Since the condenser and lens must have large working distances, mirror lenses should be used. With the device described, it should be possible to carry out preventive examinations without exposure to radiation. Since it is known that some tumorous tissues have different absorption properties for near infrared than normal tissues, a certain differentiation of the pathological changes should also be possible through a suitable choice of the wavelength.

2. Eine weitere Möglichkeit zur diagnostischen Anwendung von Infrarotstrahlung besteht darin, statt dem konfokalen- das Prinzip der Computertomographie zu verwenden. Hierbei könnte man auf der einen Seite als kollimierte Strahlungsquelle einen leistungsmäßig angepaßten Infrarotlaser und auf der anderen Seite einen Photomultiplier verwenden, dem zur Eliminierung von Streustrahlung eine Röhre mit Ringblenden vorgeschaltet ist. 2. Another possibility for the diagnostic application of Infrared radiation is there instead of confocal - that Use principle of computed tomography. Here you could on the one hand as a collimated radiation source performance-adjusted infrared laser and on the other Use a photomultiplier on the side to eliminate Scattered radiation is upstream of a tube with ring diaphragms.  

Diese Anordnung müßte wie beim herkömmlichen Computertomographen um das Objekt gescannt werden. Die vom Photomultiplier registrierte Photonenflüsse wären die Meßwerte, aus denen mit den bekannten Algorithmen der Computertomographie die Bilder berechnet würden.This arrangement would have to be the same as with a conventional computer tomograph to be scanned around the object. The one from the photomultiplier registered photon fluxes would be the measured values from which with the known algorithms of computed tomography would be calculated.

3. Im dritten Patentanspruch wird ein mikroskopisches Verfahren zur Biolumineszensmessung in dickeren Gewebeschnitten beschrieben. Biochemische Reaktionen sind mit der Abstrahlung von Photonen spezifischer Wellenlänge im Infrarotbereich verbunden. Wenn es nun gelänge, diese Infrarotemissionen selektiv durch Bandpaßfilter mit dem Mikroskop darzustellen, wäre es möglich, biochemische Vorgänge in Zellen direkt zu verfolgen. Als Detektoren können hierbei z. B. Infrarot CCDs (auf der Basis von mit Platin dotiertem Silizium) verwendet werden. Um in dickeren Gewebeschnitten beobachten zu können, muß in einer Zwischenbildebene des Mikroskops eine Nipkowsscheibe (evtl. mit Spiralschlitzen) zur Eliminierung von Streustrahlung eingesetzt werden. Eine mögliche Ausführung ist in Abb. 2 für ein Invertoskop skizziert, Kondensor und Fluoreszenslampe in der Abbildung sind für die hier beschriebene Anwendung entbehrlich. Die Nipkowschiebe kann mit entsprechender Optik auch in andere Ebenen eingesetzt werden, in denen ein Zwischenbild entworfen wird, z. B. im nach hinten oder seitlich ausgespiegelten Strahlengang der Fluoreszenslampe. Da der ganze Schnitt Selbststrahler ist, genügt eine Nipkowscheibe. Mit einer gekühlten CCD-Kamera kann minutenlang integriert werden, so daß auch schwächste Photonenemissionen gemessen werden können. Bei Verwendung einer herkömmlichen CCD auf Siliziumbasis könnten auch mögliche Photonenemissionen im sichtbaren Bereich gemessen werden. Sollen schnellere Vorgängen untersucht werden, wäre die Vorschaltung eines Bildverstärkers möglich. Bei Verwendung von langbrennweitigen Spiegelobjektiven, könnte das Mikroskop bei geringer Vergrößerung als Thermokamera verwendet werden.3. The third claim describes a microscopic method for measuring bioluminescence in thicker tissue sections. Biochemical reactions are associated with the emission of photons of a specific wavelength in the infrared range. If it were possible to selectively display these infrared emissions using bandpass filters with a microscope, it would be possible to directly follow biochemical processes in cells. As detectors, z. B. Infrared CCDs (based on platinum-doped silicon) can be used. In order to be able to observe in thicker tissue sections, a Nipkows disk (possibly with spiral slits) must be used in an intermediate image plane of the microscope to eliminate scattered radiation. A possible embodiment is sketched in Fig. 2 for an invertoscope, the condenser and fluorescent lamp in the figure are unnecessary for the application described here. With the appropriate optics, the Nipkow slide can also be used in other levels in which an intermediate image is designed, e.g. B. in the back or side mirrored beam path of the fluorescent lamp. Since the entire cut is self-radiating, a Nipkow disc is sufficient. A cooled CCD camera can be integrated for several minutes so that even the weakest photon emissions can be measured. When using a conventional silicon-based CCD, possible photon emissions in the visible range could also be measured. If faster processes are to be investigated, an image intensifier could be connected upstream. When using long focal length mirror lenses, the microscope could be used as a thermal camera at low magnification.

Claims (3)

1. Optisches System zur Darstellung von Strukturen in biologischem Gewebe, dadurch gekennzeichnet, daß der Tomograph mit Infrarotstrahlung und dem Prinzip der konfokalen Abbildung arbeitet.1. Optical system for displaying structures in biological tissue, characterized in that the tomograph works with infrared radiation and the principle of confocal imaging. 2. Optisches System nach Anspruch 1, dadurch gekennzeichnet, daß es mit Infrarotstrahlung und dem Prinzip der Computertomographie arbeitet.2. Optical system according to claim 1, characterized in that it with infrared radiation and the principle of computer tomography is working. 3. Optisches System, das in Kombination mit dem System der konfokalen Abbildung die Infraroteigenstrahlung von biologischen Gewebe sichtbar macht. Es kann makroskopische als konfokale Thermokamera oder mikroskopisch als konfokales Biolumineszensmikroskop ausgeführt sein.3. Optical system that in combination with the system of confocal figure the infrared natural radiation from biological Makes tissue visible. It can be macroscopic as confocal Thermal camera or microscopic as a confocal Bioluminescence microscope.
DE4015988A 1990-05-18 1990-05-18 IR tomograph based on confocal imaging principal - uses either IR radiation source for computer tomography or IR radiation from cells in biological tissue Withdrawn DE4015988A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE4015988A DE4015988A1 (en) 1990-05-18 1990-05-18 IR tomograph based on confocal imaging principal - uses either IR radiation source for computer tomography or IR radiation from cells in biological tissue

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE4015988A DE4015988A1 (en) 1990-05-18 1990-05-18 IR tomograph based on confocal imaging principal - uses either IR radiation source for computer tomography or IR radiation from cells in biological tissue

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DE4015988A1 true DE4015988A1 (en) 1991-11-21

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4307411A1 (en) * 1993-03-09 1994-09-15 Mira Gmbh Dental examination instrument
DE19544187A1 (en) * 1995-11-28 1997-06-05 Telefunken Microelectron Thermal imaging system is triggered by, e.g. heart beat
US5880880A (en) * 1995-01-13 1999-03-09 The General Hospital Corp. Three-dimensional scanning confocal laser microscope
NL1009296C2 (en) * 1998-06-02 1999-12-03 Gerold Staudinger Use of Nipkow disc to scan optically three-dimensional object in discrete parallel planes for computer resolution of contours
US6548796B1 (en) 1999-06-23 2003-04-15 Regents Of The University Of Minnesota Confocal macroscope
WO2003042670A1 (en) * 2001-11-13 2003-05-22 Rensselaer Polytechnic Institute Method and system for performing three-dimensional teraherz imaging on an object

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4307411A1 (en) * 1993-03-09 1994-09-15 Mira Gmbh Dental examination instrument
US5880880A (en) * 1995-01-13 1999-03-09 The General Hospital Corp. Three-dimensional scanning confocal laser microscope
US5995283A (en) * 1995-01-13 1999-11-30 General Hospital Corporation Three-dimensional scanning confocal laser microscope
DE19544187A1 (en) * 1995-11-28 1997-06-05 Telefunken Microelectron Thermal imaging system is triggered by, e.g. heart beat
NL1009296C2 (en) * 1998-06-02 1999-12-03 Gerold Staudinger Use of Nipkow disc to scan optically three-dimensional object in discrete parallel planes for computer resolution of contours
US6548796B1 (en) 1999-06-23 2003-04-15 Regents Of The University Of Minnesota Confocal macroscope
WO2003042670A1 (en) * 2001-11-13 2003-05-22 Rensselaer Polytechnic Institute Method and system for performing three-dimensional teraherz imaging on an object

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