WO2014052040A2 - Oxymétrie absolue non invasive du tissu cérébral - Google Patents

Oxymétrie absolue non invasive du tissu cérébral Download PDF

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Publication number
WO2014052040A2
WO2014052040A2 PCT/US2013/059610 US2013059610W WO2014052040A2 WO 2014052040 A2 WO2014052040 A2 WO 2014052040A2 US 2013059610 W US2013059610 W US 2013059610W WO 2014052040 A2 WO2014052040 A2 WO 2014052040A2
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WO
WIPO (PCT)
Prior art keywords
optical
tissue
inner layer
optical signal
parameters characterizing
Prior art date
Application number
PCT/US2013/059610
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English (en)
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WO2014052040A3 (fr
Inventor
Bertan HALLACOGLU
Sergio Fantini
Angelo SASSAROLI
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Tufts University
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.)
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Application filed by Tufts University filed Critical Tufts University
Publication of WO2014052040A2 publication Critical patent/WO2014052040A2/fr
Publication of WO2014052040A3 publication Critical patent/WO2014052040A3/fr

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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
    • A61B5/14551—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 for measuring blood gases
    • A61B5/14553—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 for measuring blood gases specially adapted for cerebral tissue

Definitions

  • This disclosure relates to measuring characteristics of extracerebral and cerebral tissue.
  • NIRS Near-infrared spectroscopy
  • This technology is useful for identifying dark-colored deoxygenated hemoglobin and red-colored oxygenated
  • hemoglobin molecules within red blood cells as well as to measure the relative amounts of the molecules to determine whether there is adequate oxygenation. Because brain cells and organ tissue die within minutes without proper
  • a method for determining tissue properties by optical sensing includes applying an optical signal to each of a plurality of input locations on the surface of a body; sensing transmission through the body of the optical signal at an output location on the surface of the body, each input location being separated from the output
  • the layers including at least one inner layer and an outer layer between the at least one inner layer and the surface of the body, the parameters including parameters
  • Embodiments of this aspect of the invention may include one or more of the following features.
  • the optical signal includes a temporally modulated optical signal
  • the at least one transmission characteristic includes a modulated transmission characteristic.
  • the modulated transmission characteristic can include at least one of a phase and an attenuation of the modulated
  • the optical signal includes narrow bandwidth optical signals in a red or near infra-red spectral band.
  • the parameters can further include parameters
  • characterizing optical properties of the outer layer or can include parameters characterizing a thickness of the outer layer .
  • the separation distances include distances smaller than the thickness of the outer layer and distances greater than the thickness of the outer layer.
  • the method includes applying a joint estimation procedure to determine
  • the optical properties include an absorption characteristic and a diffusion characteristic.
  • the at least one metabolic characteristic of the at least one inner layer characterizes an oxygen saturation of tissue of the at least one inner layer.
  • the outer layer includes bone tissue of a head, and the at least one inner layer comprises cerebral tissue.
  • the method further includes applying an optical detector to the surface of the body for sensing the optical signal. Applying the optical signal can include directing a collimated optical beam through free space to the input locations on the surface using one or more automatically controlled optical elements, such as a controlled mirror or prism for sweeping the optical beam across the surface of the body.
  • the method can further include presenting the at least one metabolic characteristic to a user.
  • the method can further include generating the optical signal in a handheld device, and presenting the at least one metabolic characteristic on a display of the device, and controlling an optical element of the device to sweep a collimated optical beam across the surface of the body to apply the optical signal to the plurality of input
  • software stored on a computer-readable medium includes instructions for causing a data processing system to control application of an optical signal to each of a plurality of input locations on a surface a body; accept data representing a sensing of a transmission of the optical signal through the body to an output location on the body; process the accepted data to determine parameters characterizing at least two tissue layers below the surface of the body, the layers including at least one inner layer and an outer layer between the at least one inner layer and the surface of the body, the parameters including parameters characterizing optical properties of the at least one inner layer; and use the parameters characterizing the optical properties of the at least one inner layer to determine at least one metabolic characteristic of tissue in said layer.
  • an optical signal generator for generating an optical signal
  • a controllable optical element for generating an optical signal
  • the circuitry is configured to accept a signal representing characteristics of transmission of the optical signal to the detector; process the accepted data to determine parameters characterizing at least two tissue layers below the surface of the body, the layers including at least one inner layer and an outer layer between the at least one inner layer and the surface of the body, the parameters including parameters characterizing optical properties of the at least one inner layer; and use the parameters characterizing the optical properties of the at least one inner layer to determine at least one metabolic characteristic of tissue in said layer.
  • the circuitry further includes a software controlled processor.
  • brain oximetry significantly improve the accuracy, diagnostic value and reliability of absolute brain oximetry. More accurate brain oximetry measurements will improve efforts in the early detection of cerebral ischaemia, vascular cognitive impairment, assessment of recovery from strokes, and functional brain studies. Furthermore, this invention can enhance the potential of brain oximetry in predicting clinical outcome of a variety of surgical procedures.
  • FIG. 1 is a schematic representation (not to scale) of a portion of cerebral tissue, overlying extracerebral tissue and parameters associated with that tissue.
  • FIG. 2 is a block diagram of a system for measuring the desired blood volume and oxygenation characteristics of that tissue.
  • FIG. 3 is a diagram illustrating the relationship between measurement parameters, tissue parameters and the desired blood volume and oxygenation characteristics of that tissue.
  • FIG. 4A shows amplitude attenuation as a function of
  • FIG. 4B shows phase shift as a function of source-detector separation for both measured and fitted data.
  • a system is used to make multiple frequency-domain measurements on the human head and to use those measurements to
  • extracerebral tissue scalp, skull and dura
  • the thickness and optical characteristics can in turn be used to provide increased accuracy in the measurement of oxygenation characteristics of the tissue, such as
  • extracerebral tissue blood volume eBV
  • extracerebral hemoglobin oxygen saturation SeC> 2
  • cerebral blood volume cBV
  • cerebral hemoglobin oxygen saturation SCO 2
  • NIR near infrared
  • the detected photons are received by optical fiber 20 that is moveable along the surface of head 12 such that the spacing (pi) varies relative to the point of incidence 10.
  • the amplitude (a ⁇ ) and phase (cpi) of the light received by optical fiber 20 at multiple spacings of pi are used to determine the thickness (eTT) of the extracerebral tissue as well as the optical characteristics of the underlying tissue.
  • optical characteristics include the following absorption and scattering coefficients: gxtracerebral tissue absorption coefficient at wavelength X lr ⁇ ' ⁇ [1, ⁇ 11 is the extracerebral tissue reduced scattering coefficient at wavelength ⁇ , ⁇ ⁇ [1, ⁇ 21 is the extracerebral tissue absorption coefficient at wavelength ⁇ 2 ⁇ ' S [I ' ⁇ 2 ' is the extracerebral tissue reduced scattering coefficient at wavelength ⁇ 2 ; ⁇ 3 [2, ⁇ 11 is the cerebral tissue absorption coefficient at wavelength X 1 ; ⁇ , ⁇ [2, ⁇ 11 is the cerebral tissue reduced scattering coefficient at wavelength ⁇ ; cerebri tissue absorption coefficient at wavelength ⁇ 2 ; ⁇ '3 ' is the cerebral tissue reduced scattering coefficient at wavelength ⁇ 2 .
  • the instrumentation setup for making the measurements includes a handheld probe 30 that is connected to a tissue oximeter 32 and a computer 34.
  • Computer 34 receives and provides signals for controlling handheld probe 30 and tissue oximeter 32.
  • computer 34 receives the amplitude (a ⁇ ) and phase (cpi) of the modulated light received by optical fiber 20 at the
  • extracerebral tissue blood volume eBV
  • extracerebral hemoglobin oxygen saturation Se0 2
  • cerebral blood volume cBV
  • Handheld probe 30 includes a housing 36 which encloses a fiber optic collimator 38, a moveable mirror 40 and the optical fiber 20 that contacts the skin of the patient.
  • Collimator 38 receives the divergent light 41 from light sources 50, 52 and passes the collimated light to a
  • moveable mirror 40 rotates about an axis 47 such that the point of incidence if the
  • the rotatable optical mirror 40 advantageously scans the light away and back relative to the optical fiber 20, covering a source- detector range of about 7 mm to about 50 mm without
  • piezoelectric type driving motor rotates optical mirror 40 to illuminate the forehead at a range of distances.
  • other mechanisms e.g., linear translator
  • use of a moveable mirror allows for faster scanning and
  • miniaturization of the device which in turn allows for a hand-held probe configuration.
  • Tissue oximeter 32 houses light sources 50, 52, detector 18, multiplexing circuitry 66 and RF circuitry 68.
  • light sources 50, 52 are fiber-coupled laser diodes, one emitting at 690 nm and the other at 830 nm. Light sources at these wavelengths correspond to relatively flat portions of the absorption spectra of oxy ⁇ hemoglobin and deoxy-hemoglobin .
  • light sources 50, 52 can be in the form of light emitting diodes (LEDs) .
  • Optical fibers 60, 62 having active diameters of 2-3 mm deliver the 690 nm and 830 nm light to collimator 38.
  • Tissue oximeter 32 includes a multiplexing circuit 66 that turns the light sources 50, 52 on and off in sequence so that only one source is on at any given time.
  • the multiplexing rate which determines the on-time of each light source, is adjustable by computer 34.
  • a typical multiplexing rate of 100 Hz corresponds to a 10 msec on- time per diode.
  • Tissue oximeter includes detector 18 which in this embodiment is a photodiode that is optically coupled to optical fiber 20.
  • detector 18 receives the modulated light collected and guided by optical fiber 20.
  • RF circuitry 68 modulates the output of light sources 50, 52 and realizes a heterodyne detection scheme to downconvert the received signals from detector 18 to a lower frequency at which amplitude (ai) and phase (cpi) of the modulated light are more easily determined.
  • computer 34 stores software
  • Parameter estimator module 70 including a parameter estimator module 70 and an oximetry predictor module 72.
  • Parameter estimator module 70 includes a parameter estimator module 70 and an oximetry predictor module 72.
  • Parameter estimator module 70 uses a Levenberg-Marquardt algorithm to minimize the error between the model and the acquired data set, by iteratively modifying the nine
  • the estimated thickness eTT and parameters associated with the cerebral tissue 102 - namely y a [2, ⁇ 1] , ⁇ - s [2, ⁇ 1] , y a [2, ⁇ 2] , ⁇ ' s [2, ⁇ 2] are then forwarded to oximetry predictor 72 to generate oxygenation characteristics of the extracerebral and cerebral tissue, such as extracerebral tissue blood volume (eBV) , extracerebral hemoglobin oxygen saturation (SeC> 2 ) , cerebral blood volume (cBV) and cerebral hemoglobin oxygen saturation (SCO 2 ) .
  • a least squares estimate of ⁇ is made, according to:
  • ⁇ and A are the theoretical phase and amplitude predicted by a two-layer diffusion model which may be calculated numerically.
  • the separation p t is a separation between a point of incidence of a collimated beam, which is not necessarily at a right angle of incidence onto the tissue, and optical fiber
  • amplitude attenuation (a.u.) and phase shift (in degrees) are shown as a function of the separation between the light sources 50, 52 (at the point of incidence) and optical coupler 20.
  • Small circles indicate simulated data from a two-layered medium, while the lines indicate the best theoretical fit to the data.
  • the deviations from linearity in the data of FIGS. 4A and 4B are indicative of the two-layered nature of the medium, and the excellent theoretical fit demonstrates the accuracy of the diffusion model.
  • the table below one can see measured values of the absorption and reduced scattering coefficients along with the thickness of the extracerebral tissue using the methodology described above. The results indicate the high accuracy of the method of this invention.
  • tissue beds including skeletal muscle, breast, splanchnic, renal, and spinal cord.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Optics & Photonics (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

La détermination des propriétés des tissus par détection optique comprend les étapes consistant à : appliquer un signal optique à des emplacements d'entrée à la surface d'un corps; détecter la transmission du signal optique à travers le corps à un emplacement de sortie à la surface du corps, chaque emplacement d'entrée étant séparé de l'emplacement de sortie par une distance de séparation le long de la surface du corps; déterminer une caractéristique de la transmission du signal optique entre chacun des emplacements d'entrée et l'emplacement de sortie; appliquer une procédure implémentée par ordinateur afin de traiter la caractéristique de transmission déterminée, afin de déterminer les paramètres caractérisant deux couches de tissus sous la surface du corps, les couches comprenant une couche interne et une couche externe entre la couche interne et la surface du corps, les paramètres caractérisant les propriétés optiques de la couche interne; et utiliser les paramètres caractérisant les propriétés optiques de la couche interne pour déterminer une caractéristique métabolique des tissus composant la couche.
PCT/US2013/059610 2012-09-27 2013-09-13 Oxymétrie absolue non invasive du tissu cérébral WO2014052040A2 (fr)

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US201261706275P 2012-09-27 2012-09-27
US61/706,275 2012-09-27

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030040664A1 (en) * 2000-01-12 2003-02-27 Suresh Thennadil Method and apparatus for path normalization of light transport in tissue
US20100056928A1 (en) * 2008-08-10 2010-03-04 Karel Zuzak Digital light processing hyperspectral imaging apparatus

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030040664A1 (en) * 2000-01-12 2003-02-27 Suresh Thennadil Method and apparatus for path normalization of light transport in tissue
US20100056928A1 (en) * 2008-08-10 2010-03-04 Karel Zuzak Digital light processing hyperspectral imaging apparatus

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FANTINI ET AL.: 'Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy.' PHYS. MED. BIOL., [Online] vol. 44, 1999, pages 1543 - 1563 Retrieved from the Internet: <URL:http://www.nmr.mgh.harvard.edulPMI/PDF/Fantini_PMB_44_1543_1999.pdf> *
ISS, INC.: 'OxiplexTS. ISS, Inc.', [Online] 2001, Retrieved from the Internet: <URL:http://www.iss.com/resources/pdf/brochures/ISS_OxiplexTS_Brochure.pdf> [retrieved on 2014-02-02] *

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