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
• • 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
  • A61B5/1464—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 specially adapted for foetal tissue

Definitions

• the present invention relates to a method and apparatus for monitoring cerebral oxygenation (i.e., a Cerebral Oxygenation Monitor or COM), particularly in the intrauterine environment.
• the method includes measuring light scattering parameters of light directed through the cerebral cortex.
• BACKGROUND Fetal brain injury resulting from hypoxia and ischemia during labor is an important cause of death and long-term disability.
• little is known about fetal brain oxygenation and hemodynamics because there are currently no satisfactory clinical techniques for fetal monitoring.
• Intrapartum fetal evaluation is used to prevent neonatal illness and death as well as intrapartum fetal death.
• Intermittent auscultation was originally utilized for this purpose, and remains acceptable for monitoring "low risk" patients.
• EFM subsequently was advocated as a method of evaluation that would lead to decreased cerebral palsy, neonatal and intrapartum death rates. Although it places less of a demand on nursing staff, allows continuous and objective recording of information (fetal and uterine), and allows improved detection of patterns of fetal distress that are missed by auscultation, its benefit over no monitoring has not been proven.
• Fetal heart rate patterns of distress may be associated with fetal acidemia, hypoxemia and acidosis.
• Abnormal fetal heart rate patterns although a good predictor of fetal distress, are not good predictors of cerebral palsy.
• EFM is reassuring when normal. When abnormal, correct ---diagnosis of the problem requires an attendant skilled in EFM interpretation and ancillary procedures such as fetal scalp stimulation and scalp pH monitoring, vibroacoustic stimulation, ultrasound, etc. '
• the drawback in these methods is that they do not provide a direct assessment of fetal brain oxygenation, which is ultimately the most important variable in determining whether an infant will suffer from long-term neurologic injury or succumb to death.
• a method of fetal evaluation for those infants with a distress pattern that would allow detection of cerebral hypoxia is needed.
• the EFM is a screening test.
• the diagnostic tests detailed above have lead to increasing cesarean section rates with no reduction in cerebral palsy and a minimal reduction in intrapartum death.
• a testing modality that would allow clinicians a more direct method of evaluating cerebral oxygenation would target the hypoxic fetus and thus reduce the number of unnecessary - cesarean sections performed for the misperception of "fetal distress," and in turn decrease maternal morbidity and mortality, as well as length of hospital stay and, thus, lower medical costs.
• An instrument according to different aspects of the present invention addresses at least three different clinical needs.
• the first is continuous non-invasive monitoring of fetal cerebral oxygenation during labor and delivery.
• a second aspect of the invention is a postpartum imager.
• the imager has a position sensor on the probe and a high resolution video display. Images will resemble diagnostic ultrasound B-scans.
• the technology used in the postpartum imager utilizes identical laser light sources, detectors and signal processing as the COM.
• a three dimensional image is produced by overlaying many individual COM readings taken from different volumes of the newborn head on a display. The different sample volumes can be obtained in two ways. First, a source- detector pair can be positioned at different locations on the head similar to an ultrasound B-scan. Alternatively, an array of source-detector pairs can take a sequence of sample volumes similar to computed tomography.
• the third aspect of the invention is an antepartum monitor. Because the instrument can penetrate 8-10 cm of tissue, fetal cerebral oxygenation images can be obtained through the mothers abdomen.
• the principle of the antepartum imager is identical to the postpartum imager.
• the specially conditioned laser light penetrates the additional soft tissue of the mother and the same banana shaped sample volume is measured. Roughly 50% of the middle of the sample volume is fetal cerebral tissue.
• Fetal tissue is differentiated from maternal tissue on the resulting three dimensional image by the dark outline of the fetal skull: Comparison of the Present Invention With Fetal Pulse Oximeters ' Fetal pulse oximeters have been in development for several years.
• This device utilizes a modification of adult finger probe transmission technology to perform reflectance pulse oximetry on intrauterine fetal cheeks.
• the probe is attached to the fetal cheek and held in place by pressure from the uterine wall.
• investigators outside of the United States have been evaluating fetal pulse oximeters for several years and conclude that the current generation of fetal pulse oximetry sensors is not improving the quality of combined monitoring of fetal heart rate and fetal scalp blood analysis. This is not the case for a COM according to the present invention as shown in the following comparison with the fetal pulse oximeter.
• COM is a near infrared spectrometer (NIRS) that uses laser diodes for the optical source.
• Laser diodes have adequate power at a specific wavelength to penetrate fetal hair, scalp, and skull into deep gray and white matter, while remaining comfortably within the safety standards.
• Fetal pulse oximeters use LEDs for optical sources that emit a weaker broad spectrum light beam. The significance of the difference in optical source lies in the ability of COM to measure the lower cerebral tissue oxygenation rather than the cheek saturation measured with fetal oximeters.
• a second difference is that the COM intrauterine probe is held in place by suction, which has been shown to effectively maintain contact.
• Spectrometers The analysis of absorption and scattering properties of deep brain tissue is an important problem in fetal and neonatal health, in particular for determining chromophore concentrations in tissue of hemoglobin (Hb), oxyhemoglobin (Hb0 2 ) and cytochrome oxidase.
• Conventional near infrared spectrometers (NIRS) allow the changes in chromophore concentrations to be calculated from changes in the light intensity diffusely reflected from the tissue surface.
• NIRS near infrared spectrometers
• the absolute concentrations of these chromophores i.e. the absolute absorption coefficient, cannot easily be inferred as the scattering of trie light in the tissue must be taken into account.
• Total hemoglobin is the sum of all the different types of hemoglobin.
• Hb concentration is the amount of deoxygenated blood and Hb02 concentration indicates how much oxygenated blood is present.
• the significance of absolute Hb02 concentrations is it quantifies the amount of oxygen in the tissue. Significant concentrations of Hb indicates the tissue is not being oxygenated properly.
• Absolute hemoglobin concentrations quantify the amount of hemoglobin and oxygen is tissue.
• the measurement of these parameters provides significantly more information than Saturation, the ratio of Hb02 to total hemoglobin.
• the Saturation ratio does not indicate how much hemoglobin or oxygen is present.
• An instrument according to the present invention is significantly less complex than conventional near infrared spectrometers, because it measures slight changes in tissue absorption produced by small optical source wavelength changes.
• the instrument gives an early-warning of cerebral injury through intrauterine monitoring.
• the instrument will also lower the cost of health care delivery because it is estimated that 25%-35% of all C-sections could be avoided with the monitoring capability provided by the invention.
• a probe is placed over a fetal scalp for probing through the skull into the cortex.
• Probe components include the probe body containing a light source, common detector, and a cable leading from the probe body to the monitor.
• the probe body consists of a flexible circuit with electrical contacts for the detector and cable.
• the flexible circuit is preferably encapsulated in an optical grade silicon which allows the probe to conform to the curvature of the skull.
• Light passes through the cortex in a banana shaped path from the light source to the common detector. Reflected light is measured at the detector, amplified and transmitted via the cable to the monitor.
• the cerebral oxygenation monitor (COM) allows evaluation of deep gray and white matter of the fetal brain, and measures brain tissue saturation, Hb and HbOj- This is an improvement over the new fetal pulse oximeters (which measure arterial saturation) at an equivalent cost.
• the COM is a diagnostic test that is in one embodiment noninvasive to the fetus (rupture membranes required for its placement) to be used in those patients where EFM suggests the fetus is at risk.
• the parameters measured may provide vital information including: evaluation of "fetal distress" patterns — knowing brain tissue oxygen saturation will more precisely determine whether the fetus is at true risk of long-term neurologic injury or death; and evaluation of total hemoglobin — in infants anemic due to iso-immunization or vasa previa, possible conservative management of their delivery could be allowed.
• the COM thus is of great potential value in obstetrics. Intermittent and continuous use of its parameters in the "at risk" fetus may facilitate an improvement in fetal and maternal health.
• Optimal Spectroscopic Source Vertical Cavity Surface Emitting Lasers
• the COM may utilize vertical cavity surface emitting laser (VCSEL) optical sources that have many important advantages over other types of lasers.
• VCSEL vertical cavity surface emitting laser
• a VCSEL approach may be selected for COM because: VCSELs are inherently much simpler than other optical source systems; the emission wavelength of VCSELs is controlled by temperature rather than a mechanical system; VCSELs are small and low cost because they are manufactured with bulk semiconductor technology; VCSELs can be attached directly to the fetal head rather than through a fiber; VCSELs are low power but can be built in arrays that meet the power requirements to penetrate fetal hair and bone; and VCSELs at different wavelengths can be placed on the same probe.
• VCSEL vertical cavity surface emitting laser
• an aspect of the invention includes simultaneously measu ⁇ ng at two wavelengths, such as 760 nm and 830 run, wherein both arrays are mounted in a single fetal probe.
• the use of VCSELs is a system similar to the disclosed system is believed to be unknown in the prior art, and represents an important technical advance.
• Technical Rationale Different experimental approaches have been developed for the measurement of absolute absorption coefficients ( ⁇ a ) and scattering coefficients ( ⁇ s ') t in highly scattering media. Reflected intensity measurements for different distances between light source and detector can be used. Alternatively, measurements can be based upon the time of flight of the light in tissue in addition to the reflectance.
• IMLS Intensity modulated laser spectrometers
• IMLS Intensity modulated laser spectrometers
• the phase difference is approximately proportional to the mean time of flight of the light in the medium. . It has been.shown that, for a fixed modulation frequency, ⁇ a and ⁇ s ' can be inferred from the intensity and phase data obtained at different source detector distances. Alternatively, single distance, multiple modulation frequency ' measurements can be used. All of these methods are based upon fitting ⁇ a and ⁇ s ' to diffusion equation solutions for light transport in the medium.
• the present invention includes a method for the determination of absorption coefficients.
• the basic premise is that small changes in the absorption coefficient induce changes in diffuse light intensity, phase, and modulation depth, and that the ratio of these changes is primarily independent of the scattering properties of the medium. This ratio provides a good estimate of the absolute absorption coefficient. The approximation is only valid over a certain range of ⁇ a and ⁇ s ' values, however it encompasses the range found in biological tissues for near infrared wavelengths. Similarly, the ratio of the changes in intensity and phase, induced by variation in the source wavelength, allows ⁇ a to be estimated. Furthermore, ⁇ s ' can be inferred based upon the estimated ⁇ a value. The main advantages of the suggested method for the in vivo monitoring of hemoglobin concentration and oxygen saturation is its simplicity.
• FIG. 1 is a schematic representation of an overview of a probe system according to an aspect of the invention.
• FIG. 2 is a schematic representation of a COM according to an aspect of the present invention.
• FIG. 3 is a schematic representation of another probe according to an aspect of the invention.
• FIG. 4 is a schematic representation of the electronics associated with the probe of FIG. 3.
• FIG. 5 is a view of the present invention showing its utility in use in a typical application.
• DETAILED DESCRIPTION Overview A schematic representation of an intrauterine probe apparatus according to the present invention is shown in FIG. 1.
• a probe 10 has components including a probe body 12 containing a light source 14, a common detector 16 and a cable 18 to a monitor M.
• the probe body 12 consists of a flexible circuit with electrical contacts for the detector 16 and cable 18.
• the flexible circuit is encapsulated in an optical grade silicon which allows the probe to conform to the curvature of the skull.
• the dotted ' line L through the cortex C is one possible light path from the light source 14 to the common detector 16. Reflected light is measured at the detector 16, amplified and transmitted via the cable 18 to the monitor M.
• Analytical expressions for the phase ⁇ and the modulation depth M ' (the ratio of the AC and DC components of the modulated laser beam) are derived by performing a Fourier transformation of the temporal resolved impulse response of the reflectance R(r,t) to give
• V_ is to a good approximation a linear function of ⁇ a .
• the influence of ⁇ s ' on V a is even smaller than its influence on Q a . Consequently, measuring Va gives a more precise estimate of ⁇ a than measuring Q a .
• the optical source 14' is an Environmental Optical Sensors Inc. (EOSI) 2010 tunable laser diode.
• the 2010 has a motorized external cavity capable of sweeping the wavelength +/- 10 nm.
• EOSI 755 nm and 800 nm distributed feedback (DFB) laser diodes were installed to obtain respective wavelength measurements.
• the laser diode is amplitude modulated at 195.6 MHz with a signal from the Lock-In Amp 20.
• the 195.6 MHz modulation frequency was chosen because the PMT detector 16 has the best signal to noise ratio at this frequency.
• Each laser diode has a corresponding Optics For Research (OFR) VPO isolator 22.
• the laser beam was put into the fiber by an OFR Launcher 24.
• a 1.0 meter OFR near infrared fiber 26 transports the light to the tissue phantom or baby head.
• the COM probe detector 16' is a Hamamatsu HC120 Photomultipler Tube (PMT) detector (Det) positioned 20 mm from the fiber on the tissue phantom or baby. This results in a depth penetration of 17 mm with a banana shaped optic path in the phantom or baby (see L of FIG. 1).
• the detector output goes to the input of the Stanford Research SR844 RF Lock-In Amplifier 20.
• Amplitude and phase difference of the RF modulation signal are digitized at 10 KHz with a National Instruments PCI- 1200 Analog to Digital converter 28.
• a HP 8280 Pavilion computer 30 running Labview 5 from National Instruments controls laser wavelength and initiates data acquisition through a RS232 serial interface, connected to a Laser Control and Power Supply 32.
• FIGs. 3 and 4 Another embodiment of the invention is described below with reference to FIGs. 3 and 4, wherein VCSELs are used.
• the mtrauterine probe 10 is attached to the fetal head H with a low level suction from Pump 40.
• the probe 16" is a Hamamatsu R5600 photomultipHer tube (PMT) with low noise preamp.
• the source 16" is ten 760 nm laser diodes interspersed with ten 830 nm laser diodes all enclosed in a 15 mm can. See FIG. 5.
• the source optical window 14"W is anti-reflective coated glass.
• the ceramic base 14"B of the source is fastened to a thermoelectric cooler 42.
• a heat sink 44 is placed on the opposite side of the cooler 42 from the laser diodes. Room air is applied by Pump 46 to the heat exchanger 44 to speed up temperature change.
• Thermister 48 senses laser diode temperature.
• Photodetector 50 provides feedback on laser diode illumination.
• a cable 18 transmits control and data information between the probe 10 and the electronics, which are described in connection with FIG. 4.
• a thermoelectric controller 50 varies the temperature of the laser diodes 10 degrees Centigrade, which will cause a 0.2 nm change in both sets of laser diodes. The temperature is stabilized at one extreme of this temperature range to begin the measurement sequence.
• a RF Mixer 52 modulates the output of the laser diode current supply. The modulated current is applied to first the 760 nm laser diodes for 1 second and then to the 830 nm laser diodes for 1 second-through a RF Multiplexer 54.
• the TE controller 50 changes the temperature to the other extreme in about 9 seconds.
• FIG. 5 shows an operating device according to an aspect of the present invention in use in a typical application.
• a probe 10 is place upon the skull Sk of an intrauterine infant.
• the probe 10 communicates via cable 18 with a monitor M.
• the momtor M is part of a hand-held unit that also houses the other non-probe components, for example the components shown in FIG. 4 other than the cable 18.
• the monitor does not need to be of any particular type, and indeed represents any display device.
• the invention is not limited to probing fetal tissue, but instead could be used to probe any tissue or other substance, including fetal tissue during pregnancy or otherwise.
• it may be useful to probe tissue other than the brain because the body naturally protects the brain be sending it oxygen, and there may be cases where other tissue is not properly oxygenated.
• Yet another aspect of the invention is a postpartum imager.
• the imager has a position sensor on the probe and a high resolution video display. Images will resemble diagnostic ultrasound B-scans.
• the technology used in the postpartum imager utilizes identical laser light sources, detectors and signal processing as any of the COM devices and methods described above.
• a three dimensional image is produced by overlaying many individual COM readings taken from different volumes of the newborn head on a display.
• the different sample volumes can be obtained in two ways. First, a source-detector pair can be positioned at different locations on the head similar to an ultrasound B-scan. Alternatively, an array of source-detector pairs can take a sequence of sample volumes similar to computed tomography.

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• 2000
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