WO1998008076A1 - Procede pour l'examen d'un tissu biologique au moyen d'un rayonnement non ionisant - Google Patents
Procede pour l'examen d'un tissu biologique au moyen d'un rayonnement non ionisant Download PDFInfo
- Publication number
- WO1998008076A1 WO1998008076A1 PCT/DE1997/001662 DE9701662W WO9808076A1 WO 1998008076 A1 WO1998008076 A1 WO 1998008076A1 DE 9701662 W DE9701662 W DE 9701662W WO 9808076 A1 WO9808076 A1 WO 9808076A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tissue
- radiation
- photons
- doppler
- scattering
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 34
- 230000005855 radiation Effects 0.000 title claims description 16
- 238000001228 spectrum Methods 0.000 claims abstract description 17
- 230000035515 penetration Effects 0.000 claims abstract description 13
- 230000017531 blood circulation Effects 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 8
- 230000001427 coherent effect Effects 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 230000005865 ionizing radiation Effects 0.000 claims description 2
- 230000005670 electromagnetic radiation Effects 0.000 claims 4
- 239000004744 fabric Substances 0.000 claims 2
- 230000001678 irradiating effect Effects 0.000 claims 1
- 238000005259 measurement Methods 0.000 abstract description 10
- 210000004369 blood Anatomy 0.000 abstract description 9
- 239000008280 blood Substances 0.000 abstract description 9
- 230000003287 optical effect Effects 0.000 abstract description 6
- 230000003925 brain function Effects 0.000 abstract 1
- 238000002405 diagnostic procedure Methods 0.000 abstract 1
- 238000006073 displacement reaction Methods 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 34
- 239000003365 glass fiber Substances 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000005311 autocorrelation function Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000006213 oxygenation reaction Methods 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000000342 Monte Carlo simulation Methods 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 108010002255 deoxyhemoglobin Proteins 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000012854 evaluation process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000009607 mammography Methods 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000010363 phase shift Effects 0.000 description 1
- 230000008430 psychophysiology Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
- A61B5/026—Measuring blood flow
- A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
Definitions
- macarcinoma today is mainly based on the imaging method of X-ray mammography.
- parts of the public and the medical community are increasingly critical of this examination method, since damage to the irradiated tissue cannot be ruled out with certainty.
- Clinical trials include light tomographic methods in which the tissue to be examined is illuminated with visible or infrared light and the reflected or transmitted radiation is detected. Since the measured intensities depend on the optical properties of the volume irradiated in each case, it is hoped that tissue types can be distinguished and physiological or pathological changes in the tissue can be determined and localized.
- Possible applications of light tomography range from the detection of breast cancer to the registration of the oxygenation of the brain and extremities. Due to the multiple scattering of light in the tissue, the spatial resolution that can be achieved with these methods is usually only about 10-15 mm, while the established methods of medical diagnostics (X-ray computed tomography, nuclear magnetic resonance / NMR) still have structures as small as 1 mm depict. Improving the spatial resolution both in the lateral direction and in depth is therefore the primary goal of research and development [1]. 2. State of the art
- the rotation and the translation speed of a body illuminated by a laser beam can be determined by analyzing the intensity fluctuations that occur in a speckle pattern.
- these optical methods based on the speckle phenomenon have also been used in the field of medical diagnostics, for example to measure the average flow velocity of the blood in near-surface layers of tissue in vivo [2], [3].
- FIG. 1 shows the arrangement of the arrangement normally used as a photon source or in a laser Doppler measuring device.
- the lateral spatial resolution of light tomographic methods can be improved by using a gating technique [4-6].
- the tissue is irradiated with short light pulses and only those photons are detected which reach the detector within a time window of typically 100-200 ps width that limits the photon transit time.
- the mean width w of the tissue volume contributing to the measurement result decreases, see above that you can also map smaller structures.
- the distance d between the transmitting and receiving fibers is reduced and the position of the time window is adjusted accordingly with respect to the trigger signal that triggers the short-term radiation.
- the method known from [7] allows the localization of an object which absorbs IR radiation and is embedded in a strongly scattering medium.
- the positional dependence of the phase shift between the injected and the injected optical signal is measured. It is a direct measure of the mean path length of the photons in the tissue and thus also a measure of their mean penetration depth.
- the object of the invention is a method for the optical measurement of a characteristic (mean flow rate of the blood, degree of blood circulation, absorption capacity, etc.) of a biological tissue.
- a characteristic mean flow rate of the blood, degree of blood circulation, absorption capacity, etc.
- the method should make it possible to separate the photons originating from the depth range of interest from the photons scattered in higher or lower layers.
- a method with the features specified in claim 1 has these properties.
- the dependent claims relate to refinements and advantageous developments of the method according to the invention.
- the degree of blood flow to the outer cerebral cortex can be optically determined without having to open the skull. Since essentially only the photons scattered in the deeper layers of the skull are evaluated 4 are taken into account, the blood flow in the scalp does not interfere with the measurement signal.
- Photons which spread in a living and thus perfused tissue, are subject to both elastic and inelastic scattering processes.
- the photon exchanges energy with the scattering object and thereby changes its wavelength or frequency.
- This process known as the Doppler scattering of light, essentially takes place only in the areas of the tissue that are supplied with blood, the erythrocytes moving in the vessels with the blood stream acting in particular as scattering centers.
- the mean number of Doppler scattering processes per photon increases with the mean length of the distance covered by the photons in the tissue and thus also with the mean penetration depth t.
- v D the frequency change of the scattering particle
- k f and ki the wave vectors of the incident and the scattered photon.
- the Doppler scattering of the photons in the tissue results in a broadening of the frequency spectrum of the detected scattered light compared to the injected light, the extent of the broadening depending on the average number of Doppler scattering processes and therefore also depends on the average penetration depth of the photons.
- S (v) of the detected scattered light higher frequencies are consequently to be attributed to those photons that penetrated deeper into the perfused tissue and were exposed to the conditions prevailing there (flow velocity of the blood, density and number of red blood cells, etc.) were.
- Depth discrimination can therefore be achieved by subjecting the detected frequency spectrum S (v) to frequency filtering, in particular high-pass filtering ( ⁇ . The upper part of FIG. 2) or low-pass filtering. Then only those photons contribute to the measurement signal whose Doppler shift lies above or below the filter threshold, whose mean penetration depth is greater or less than a minimum value predetermined by the filter threshold. Band-pass filtering of the power spectrum S (v) ensures that only the photons scattered Doppler in a certain depth range of the tissue are evaluated.
- FIG. 3 shows the schematic structure of a laser double measuring device, which is particularly suitable for determining the degree of blood circulation in deeper layers of a biological tissue 3.
- the intensity of the primary radiation on the tissue surface is typically around 120 mW.
- the diameter of their respective end faces is comparatively small at 2r ⁇ 10-20 ⁇ m (the diameter dspeckie «• * ⁇ / NA one
- the scattered light which is frequency-shifted due to the Doppler effect, is coherently superimposed with the light not Doppler-scattered (heterodyne overlay).
- Doppler-scattered light is also mixed with Doppler-scattered light (coherent ho odyne superimposition), the beat produced in both cases containing the Doppler frequencies which are approximately proportional to the blood flow.
- the intensity of the scattered light emerging at the tissue surface and detected by the detector-side monomode glass fibers 10/11 drops considerably.
- the source-side glass fiber 8 consequently emits about 10 15 photons per second into the tissue 3.
- This value lies in the range of the maximum count rates still to be processed by single photon detectors, so that the coherent reception of the scattered light does not represent a major restriction with regard to the signal intensity and the measuring time.
- Photo ultipliers and so-called “avalanche” photodiodes are used in particular as photon detectors 12/13.
- the detector 12 (avalanche photodiode) of the first evaluation electronics is a digital correlator 14 (Brookhaven Instruments, BI 9000) AT), which determines the temporal photon autocorrelation function ⁇ I ( ⁇ ) -I (t + ⁇ )> / ⁇ I> 2.
- a computer 15 converts the temporal autocorrelation function by a
- a spectrum analyzer 16 Hewlett Packard, HP 35665 A
- the detector 13 avalanche photodiode
- the size R is the blood flow, i.e. H. the product of
- the range of functions of the average speed of the red blood cells is approximately proportional.
- Results of a Monte Carlo simulation confirm the assumption that the frequency shift of the scattered versus the incident light caused by Doppler scattering depends on the mean penetration depth of the photons in a homogeneously perfused tissue.
- Figure 4 shows the results of the simulation calculation.
- the curves are very noisy due to the small number (10 6 ) of simulated photons (in the experiment, tissue 3 is irradiated with about 10 le photons / second). Below approximately 10 kHz, the mean penetration depth t increases approximately linearly with the Doppler shift.
- differential absorption measurements can also be carried out, for example to determine the blood volume or the local degree of oxygenation of the blood.
- the tissue is illuminated with at least two radiation probes, the wavelengths of which are matched to the absorption maxima of oxyhemoglobin or deoxyhemoglobin.
- Each of the stray light components is then subjected to the evaluation process described above.
- a component with the modulation frequency (typically 70-200 MHz) is also observed in the power spectrum of the detected scattered light (see the upper part of FIG. 5).
- the Doppler shifts occur as sidebands around the signal component at the modulation frequency and can be determined and evaluated by overlay reception.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Physiology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Optics & Photonics (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
Par suite de la dispersion multiple des photons dans les tissus, la résolution locale pouvant être obtenue par phototomographie n'est actuellement que de l'ordre de 10-15 mm. Or, les procédés connus de diagnostic médical fournissent des images de fines structures atteignant 1 mm. La dispersion Doppler des photons dans des domaines tissulaires irrigués par le sang entraîne un élargissement du spectre de fréquence de la lumière détectée par rapport à la lumière du rayonnement incident, l'importance de l'élargissement dépendant du nombre moyen de processus de dispersion Doppler par photon et, par conséquent, également de la profondeur moyenne de pénétration des photons. On peut donc obtenir une discrimination en profondeur en soumettant le spectre de puissance du rayonnement de dispersion détecté à un filtrage passe-haut. Seuls les photons dont le déplacement Doppler se situe au-dessus du seuil de filtrage, ou dont la profondeur de pénétration moyenne est supérieure à une valeur minimale prédéterminée par le seuil de filtrage, contribuent alors au signal de mesure. On mentionne, comme applications, la tomographie optique, la mesure transcrânienne de la fonction cérébrale, la mesure du degré d'irrigation sanguine dans les couches tissulaires profondes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1996134152 DE19634152A1 (de) | 1996-08-23 | 1996-08-23 | Verfahren zur Untersuchung eines biologischen Gewebes mit nichtionisierender Strahlung |
| DE19634152.3 | 1996-08-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998008076A1 true WO1998008076A1 (fr) | 1998-02-26 |
Family
ID=7803538
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE1997/001662 WO1998008076A1 (fr) | 1996-08-23 | 1997-08-06 | Procede pour l'examen d'un tissu biologique au moyen d'un rayonnement non ionisant |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE19634152A1 (fr) |
| WO (1) | WO1998008076A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7251518B2 (en) | 2003-03-13 | 2007-07-31 | Nirlus Engineering Ag | Blood optode |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6526298B1 (en) | 1998-05-18 | 2003-02-25 | Abbott Laboratories | Method for the non-invasive determination of analytes in a selected volume of tissue |
| US7043287B1 (en) | 1998-05-18 | 2006-05-09 | Abbott Laboratories | Method for modulating light penetration depth in tissue and diagnostic applications using same |
| US6241663B1 (en) | 1998-05-18 | 2001-06-05 | Abbott Laboratories | Method for improving non-invasive determination of the concentration of analytes in a biological sample |
| US6662031B1 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratoies | Method and device for the noninvasive determination of hemoglobin and hematocrit |
| US6662030B2 (en) * | 1998-05-18 | 2003-12-09 | Abbott Laboratories | Non-invasive sensor having controllable temperature feature |
| EP1130998B1 (fr) * | 1998-11-18 | 2008-08-13 | LEA Medizintechnik GmbH | Dispositif pour la determination non invasive du metabolisme de l'oxygene dans des tissus |
| GB9923347D0 (en) * | 1999-10-05 | 1999-12-08 | Univ Manchester | Processing apparatus and method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4109647A (en) * | 1977-03-16 | 1978-08-29 | The United States Of America As Represented By The Secretary Of The Department Of Health, Education And Welfare | Method of and apparatus for measurement of blood flow using coherent light |
| FR2441161A1 (fr) * | 1978-10-31 | 1980-06-06 | Nilsson Gert | Procede et dispositif pour determiner des mouvements de circulation dans un liquide |
| US4223680A (en) * | 1977-06-28 | 1980-09-23 | Duke University, Inc. | Method and apparatus for monitoring metabolism in body organs in vivo |
| GB2132483A (en) * | 1982-04-07 | 1984-07-11 | Univ Manchester | A device for measuring blood flow |
| EP0284248A1 (fr) * | 1987-03-27 | 1988-09-28 | Kowa Co. Ltd. | Procédé et dispositif de diagnostic ophtalmologique |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3838396A1 (de) * | 1988-11-12 | 1990-05-17 | Poesl Hans Dr Med | Verfahren zur lokalisation von gefaessen und zur prognose von blutungen |
-
1996
- 1996-08-23 DE DE1996134152 patent/DE19634152A1/de not_active Ceased
-
1997
- 1997-08-06 WO PCT/DE1997/001662 patent/WO1998008076A1/fr active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4109647A (en) * | 1977-03-16 | 1978-08-29 | The United States Of America As Represented By The Secretary Of The Department Of Health, Education And Welfare | Method of and apparatus for measurement of blood flow using coherent light |
| US4223680A (en) * | 1977-06-28 | 1980-09-23 | Duke University, Inc. | Method and apparatus for monitoring metabolism in body organs in vivo |
| FR2441161A1 (fr) * | 1978-10-31 | 1980-06-06 | Nilsson Gert | Procede et dispositif pour determiner des mouvements de circulation dans un liquide |
| GB2132483A (en) * | 1982-04-07 | 1984-07-11 | Univ Manchester | A device for measuring blood flow |
| EP0284248A1 (fr) * | 1987-03-27 | 1988-09-28 | Kowa Co. Ltd. | Procédé et dispositif de diagnostic ophtalmologique |
Non-Patent Citations (1)
| Title |
|---|
| SCHMITT H J ET AL: "SYSTEM CONCEPTS FOR HIGH RESOLUTION OPTICAL TOMOGRAPHY SYSTEMKONZEPTE FUR HOCHAUFLOSENDE OPTISCHE TOMOGRAPHIE", LASER UND OPTOELEKTRONIK, vol. 27, no. 1, 1 February 1995 (1995-02-01), pages 43 - 47, XP000482883 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7251518B2 (en) | 2003-03-13 | 2007-07-31 | Nirlus Engineering Ag | Blood optode |
Also Published As
| Publication number | Publication date |
|---|---|
| DE19634152A1 (de) | 1998-03-05 |
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