EP0322431A1 - Procede et dispositif pour etudier les modifications cellulaires d'un etre vivant - Google Patents

Procede et dispositif pour etudier les modifications cellulaires d'un etre vivant

Info

Publication number
EP0322431A1
EP0322431A1 EP88905351A EP88905351A EP0322431A1 EP 0322431 A1 EP0322431 A1 EP 0322431A1 EP 88905351 A EP88905351 A EP 88905351A EP 88905351 A EP88905351 A EP 88905351A EP 0322431 A1 EP0322431 A1 EP 0322431A1
Authority
EP
European Patent Office
Prior art keywords
ray radiation
ray
image
value
sample
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Withdrawn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
EP88905351A
Other languages
German (de)
English (en)
Inventor
Hans-Detlef Wolf
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.)
HAMANN Georg
Original Assignee
HAMANN Georg
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from DE3720827A external-priority patent/DE3720827C1/de
Priority claimed from DE19873733267 external-priority patent/DE3733267A1/de
Application filed by HAMANN Georg filed Critical HAMANN Georg
Publication of EP0322431A1 publication Critical patent/EP0322431A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
    • G01N23/02—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by transmitting the radiation through the material
    • G01N23/06—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by transmitting the radiation through the material and measuring the absorption
    • G01N23/083—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by transmitting the radiation through the material and measuring the absorption the radiation being X-rays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material

Definitions

  • the invention relates to a method for. Examination of cell changes in a living being, in particular pathological cell changes in a person and a device for carrying out this method.
  • the invention has for its object to provide a method and an apparatus by means of which early detection of cell changes in a living being is possible with little effort and time.
  • the invention is based on the knowledge that the interaction of X-rays with the cell substance be from an immediately preceding X-ray radiation is influenced.
  • the cell substance to be examined is irradiated with two X-ray radiation pulses in direct succession.
  • the interaction of the X-rays with the cell substance is determined in each case by measuring or recording the X-ray intensity passing through or the attenuation of the X-rays.
  • the first x-ray pulse leads to excitation of the cell substance, so that the second x-ray pulse shines through the excited cell substance. It has been shown that the first X-ray pulse is weakened by the cell substance more than the immediately following second X-ray pulse. If two X-ray radiation pulses of the same spectral intensity distribution are sent directly in succession through the same cell substance, then a higher intensity passing through is measured for the second X-ray radiation pulse than for the first X-ray radiation pulse.
  • the invention takes advantage of the knowledge that the difference in the attenuation of the X-ray radiation intensity between the first and the second X-ray radiation pulse depends on the state of the cells in the irradiated substance.
  • the state of the cells in the substance can therefore be inferred from the measured difference in attenuation between the first and the second X-ray radiation pulse.
  • healthy cells of living beings have a bioelectric potential of approximately 50 to 100 mV, in humans approximately 90 to 100 mV.
  • this bioelectric potential of the cell in cancer drops to around 30 to 10 mV. It is assumed that this depolarization of the cell, which occurs in the case of cancer, is also related to the change in the cell structure, which leads to the change in the attenuation difference used according to the invention for the detection of the cell change.
  • a sample containing the cell material to be examined is irradiated with X-ray pulses of the same spectral intensity distribution and the same overall intensity in immediate succession.
  • the X-ray radiation intensity passing behind the sample is detected with a detector.
  • the difference in intensity between the second and the first X-ray radiation pulse is determined and compared with a standard value which corresponds to a healthy cell material.
  • any sample containing cell substance can be used as the sample. It can be a tissue sample from the living being.
  • a blood sample is preferred because of the simple sample collection. Since the above-mentioned depolarization of the cells occurs in cancer throughout the bloodstream, the examination of a blood sample allows an indication of cancer anywhere in the body.
  • the method according to the invention is therefore particularly suitable for simple early cancer diagnosis.
  • the use of X-rays with an essentially continuous energy spectrum, as is emitted by an X-ray tube has proven to be advantageous.
  • the upper limit energy of the X-ray spectrum is expediently around 30 keV. Higher energetic x-rays show less interaction and also make higher technical demands on the device that generates the x-rays.
  • the time interval between the two X-ray radiation pulses should be less than approx. 1 sec. With a larger time interval, the difference between the X-ray attenuation becomes too small.
  • the time interval between the two X-ray radiation pulses of approximately 100 ⁇ sec has proven to be most advantageous. At this time interval there is a well measurable difference in the X-ray attenuation and this time interval can be easily controlled in relation to the control of the X-ray source and the detector.
  • Any known petector can be used as a detector which has a sufficiently good response behavior for the entire energy spectrum of the X-ray radiation.
  • a Geiger-Müller counter or a scintillation counter is preferably used. These detectors register the penetrating X-ray intensity as a digital count rate, which can be processed electronically in a simple manner.
  • the attenuation of the X-rays of the first and the second radiation pulse can be in can easily be determined as a count rate difference.
  • the intensity can also be measured by blackening an X-ray film plate.
  • the difference in the x-ray attenuation between the first and the second x-ray pulse is not only influenced by the cell properties, but of course also depends on other physico-chemical parameters of the sample.
  • a diagnosis based on a comparison of the measured value with the standard value therefore presupposes that the measured value and the standard value refer to the same conditions with regard to these additional parameters.
  • the essential parameters of the sample are measured in addition to the X-ray measurement in a manner known per se and are used arithmetically to correct the standard value or the measured value.
  • the essential parameters that are taken into account in this way for a blood sample are the pH value (hydrogen ion concentration), the pO 2 value (oxygen concentration) and the r value (electrical conductivity).
  • the absolute intensity of the X-ray radiation must of course also be determined, for example, by a calibration measurement without a sample and taken into account in the computational evaluation.
  • the cell change can also be examined without taking a tissue sample. The area of the body containing the tissue to be examined is irradiated with the two X-ray radiation pulses in the short time interval. The radiation intensity passing through the two X-ray radiation pulses is recorded in each case, so that an X-ray image of the region containing the tissue to be examined is obtained.
  • the intensity distribution of the respective recordings of the two X-ray radiation pulses is subtracted from one another point by point in a grid. This results in the distribution of the intensity difference in which the tissue area with a pathological cell change, for example an area affected by cancer, clearly stands out from the surrounding tissue with a healthy cell structure.
  • the recording of the intensity distribution of the two X-ray radiation pulses and the difference between the two recordings can be carried out by means of technical measures known per se.
  • FIG. 1 shows the basic structure of a device for examining a sample of a cell substance
  • FIG. 2 shows an X-ray device for generating records for the difference evaluation
  • Figure 3 shows a device for evaluating with the in
  • FIG. 2 shows the device generated
  • Figure 4 shows a modified device for generating
  • Figure 5 shows another embodiment of a recording device with an evaluation device.
  • an X-ray tube 110 is operated by means of a power pack 112 and a high-voltage generator 114 with a voltage of approximately 30 kV.
  • the radiation from the X-ray tube emerging via a filter 116 is passed through a blood sample which is contained in a suitable sample receiving device 118, for example in a cuvette with a content of approximately 3 ml.
  • the X-ray radiation passing through the blood sample strikes a detector 120, for example a Geiger-Müller counter tube operating in the triggering mode.
  • the pulses from the detector 120 are counted in an electronic counter 122.
  • An electronic control 126 is put into operation via an operating unit 124.
  • the electronic controller 26 controls the X-ray tube 110 in such a way that it is at a time interval of approximately 100 msec emits two identical radiation pulses.
  • the electronic controller 126 controls the output of the electronic counter 122 in such a way that the count rate corresponding to the first x-ray pulse is fed to a first display and storage unit 128 and the count rate corresponding to the second x-ray pulse is fed to a second display and storage unit 130.
  • the count rates of the first and the second X-ray radiation pulse stored in the display and storage units 128 and 130 are fed to a computer unit 132 for arithmetical evaluation.
  • the pH value is measured in a conventional manner by means of electrodes 136 in a unit 138 and the electrical conductivity (r value) in a unit 140.
  • a drop 142 of the blood to be examined is placed on a pO 2 sensor 144 in a manner known per se and the pO 2 value is measured in a conventional unit 146.
  • the measured values of the units 138, 140 and 146 are stored via associated display and storage units 148, 150 and 152 and fed to the computer unit 132.
  • the difference between the counting rates of the second X-ray radiation pulse and the first X-ray radiation pulse is calculated in the computer unit 132 as the measured value.
  • This measured value is corrected arithmetically with the counting rate, which is measured without the sample 118.
  • the corrected measured value is then compared in the computer unit 132 with a standard value, that with a sample 118 of the blood of a healthy person was determined.
  • the deviations of these physico-chemical parameters between the currently examined sample and the sample with which the standard value was measured are taken into account in the computer unit 132.
  • a device shown in FIG. 2 comprises a conventional x-ray device with a generator 1, a radiator 2 and an electrical control 3 for the generator.
  • a cassette 4 with an X-ray film 5 provided for a first image and an X-ray film 6 provided for a second image is provided as a receiver.
  • the object 7 to be examined is placed between the radiator 2 and the cassette 4 containing the X-ray films.
  • the controller 3 is designed in such a way that, in conventional X-ray technology, two X-ray film recordings on the first and second X-ray films 5, 6 are made in quick succession by the same organ to be examined in the same position.
  • the time difference is in the range of seconds and is preferably one to three seconds or even less than one second.
  • the evaluation of the images thus generated on the two X-ray films 5, 6 takes place with the device shown in FIG. 3.
  • This comprises two video cameras 8, 9.
  • the first camera 8 is connected on the output side to an amplifier 10, which in turn is connected on the output side to a subtractor 11.
  • the output of the second video camera 9 is connected to an amplifier 12 which simultaneously reverses the phase and whose output is connected to the subtractor 11.
  • the output of the subtractor 11 is connected via an amplifier 13 directly to a first monitor 14 and also to an image memory 15.
  • the image memory is connected on the one hand to the monitor 14 and on the other hand to a microcomputer 16.
  • the microcomputer is connected to electronic data processing 17 and, moreover, to a second monitor 18.
  • the X-ray films 5 ', 6' to be evaluated are arranged at a predetermined distance in front of the video cameras.
  • a schematically indicated light source 19 for illuminating the films for evaluation is arranged on the side of the X-ray films facing away from the video cameras.
  • the two X-ray films 5 ', 6' are scanned congruently with the video cameras 8, 9.
  • the video signals generated in this process are electronically processed so that a positive and a negative video signal with mutually corresponding amplitudes are produced.
  • the subtractor 11 the signals supplied to it are subtracted.
  • the output-side difference signal is amplified in the amplifier 13 and visible on the first monitor 14 made. Image content only appears on the monitor if the difference between the two video signals is not equal to zero. This is only the case if the corresponding image content on the two films 5 ', 6 1 comes from a cancerous tissue.
  • the cause of this phenomenon lies in the different excitation energy of X-rays with normal tissue compared to cancer tissue.
  • the subtractor is set so that amplitudes of healthy tissue cancel each other out and are therefore not visible on the monitor. Only tissue that is diseased is then visible on the monitor. This makes it possible to easily and clearly differentiate cancerous tissue from normal tissue.
  • the generated image can be stored electronically in the image memory 15 and electronically evaluated with the microcomputer.
  • the device shown in FIG. 4 differs from the device described in FIGS. 2 and 3 in that electronic image storage is used instead of the X-ray films 5, 6.
  • the device comprises a generator 1, a radiator 2 and a controller 3.
  • a camera 20 that is sensitive to X-rays is provided as the image recorder.
  • the object 7 to be examined is arranged between this and the radiator 2.
  • the camera 20 is connected on the output side to an amplifier 21, which in turn is connected on the output side to an analog / digital converter 22.
  • the electronic control 3 is additionally connected to a phase reversal 23, the output of which is connected to the amplifier 21.
  • the analog / digital converter 22 is connected on the output side to a microcomputer 24, which in turn is connected on the output side to an image memory 25 and on the other hand to a digital / analog converter 26.
  • the output of the digital / analog converter 26 is in turn connected to a subtractor 27, which in turn is connected on the output side to a monitor 29 via an amplifier 28.
  • the memory 25 is additionally connected to electronic data processing 30.
  • an image is first generated by the first exposure.
  • the output signal from the camera 20 is converted accordingly and temporarily stored in the memory 25.
  • a second image is generated by the briefly following second irradiation, the amplitude signal obtained therefrom is reversed in phase via the phase inversion 23.
  • the signal thus obtained is subtracted from the buffered image in a manner comparable to that in the exemplary embodiment described above, so that only the parts which come from a diseased tissue, in particular cancerous tissue, are visible on the monitor 29 as in the previously described exemplary embodiment .
  • the device shown in FIG. 5 differs from the previously described device in that the imaging is not performed using conventional X-ray fluoroscopy, but according to the principle of computer tomography. graphic is created.
  • the device comprises a corresponding radiator 31, a generator 32 and an electronic control 33 which irradiate the object 7 to be examined in the manner customary in computer tomography.
  • a detector 34 is provided on the opposite side. This is connected on the output side to an analog / digital converter 35. This is followed by the elements 22 to 30 as in FIG. 4.
  • the electronic control 33 is designed in such a way that it repeats every pulse common in computer tomography at the brief interval described above. On the one hand, all of the impulses that occur in conventional computer tomography occur at a wide variety of angles. In addition, all impulses occur a second time at the time interval described above.
  • the detector 34 and the associated evaluation device are designed such that a first image is stored which is formed from the respective first pulses. Furthermore, a second image is stored, which comes from the respective second pulses.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)

Abstract

Pour étudier les modifications cellulaires d'un être vivant, notamment les modifications cellulaires pathologiques chez l'homme, on irradie la substance cellulaire avec deux impulsions de rayonnement X se succédant immédiatement dans le temps. On évalue ensuite la différence d'atténuation de l'intensité entre ces deux impulsions.
EP88905351A 1987-06-24 1988-06-18 Procede et dispositif pour etudier les modifications cellulaires d'un etre vivant Withdrawn EP0322431A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE3733267 1981-10-01
DE3720827A DE3720827C1 (en) 1987-06-24 1987-06-24 Method and apparatus for detecting cellular changes in a living organism
DE3720827 1987-06-24
DE19873733267 DE3733267A1 (de) 1987-10-01 1987-10-01 Verfahren und vorrichtung zum erkennen von krankhaft veraendertem gewebe

Publications (1)

Publication Number Publication Date
EP0322431A1 true EP0322431A1 (fr) 1989-07-05

Family

ID=25856890

Family Applications (1)

Application Number Title Priority Date Filing Date
EP88905351A Withdrawn EP0322431A1 (fr) 1987-06-24 1988-06-18 Procede et dispositif pour etudier les modifications cellulaires d'un etre vivant

Country Status (5)

Country Link
US (1) US5157703A (fr)
EP (1) EP0322431A1 (fr)
JP (1) JPH02500884A (fr)
AU (1) AU1954788A (fr)
WO (1) WO1988010094A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5408535A (en) * 1993-09-07 1995-04-18 Miles Inc. Video test strip reader and method for evaluating test strips
US7126121B1 (en) * 2002-06-22 2006-10-24 Purdue Research Foundation Real-time video radiation exposure monitoring system
US7205891B1 (en) 2003-09-19 2007-04-17 Purdue Research Foundation Real-time wireless video exposure monitoring system

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3848130A (en) * 1973-06-25 1974-11-12 A Macovski Selective material x-ray imaging system
US3854049A (en) * 1973-12-10 1974-12-10 Wisconsin Alumni Res Found Compensation for patient thickness variations in differential x-ray transmission imaging
DE3131651A1 (de) * 1980-08-18 1982-05-27 General Electric Co., Schenectady, N.Y. "anordnung zum subtrahieren von roentgenbildern"
US4399457A (en) * 1981-06-08 1983-08-16 General Electric Company X-Ray image digital subtraction system

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8810094A1 *

Also Published As

Publication number Publication date
AU1954788A (en) 1989-01-19
US5157703A (en) 1992-10-20
WO1988010094A1 (fr) 1988-12-29
JPH02500884A (ja) 1990-03-29

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