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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
  • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
• • 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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or 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
  • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
  • A61B5/7203—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal
  • A61B5/7207—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal of noise induced by motion artifacts
  • A61B5/7214—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal of noise induced by motion artifacts using signal cancellation, e.g. based on input of two identical physiological sensors spaced apart, or based on two signals derived from the same sensor, for different optical wavelengths

Definitions

• the present invention relates to a device, system and method for determining the concentration of a substance, such as the concentration of oxygen (oxygen saturation, Sp02), bilirubin, C02, etc., in the blood of a subject, such as a person or animal.
• a substance such as the concentration of oxygen (oxygen saturation, Sp02), bilirubin, C02, etc.
• Vital signs of a person for example the heart rate (HR), the respiration rate (RR) or the arterial blood oxygen saturation (Sp02), serve as indicators of the current state of a person and as powerful predictors of serious medical events. For this reason, vital signs are extensively monitored in inpatient and outpatient care settings, at home or in further health, leisure and fitness settings.
• HR heart rate
• RR respiration rate
• Sp02 arterial blood oxygen saturation
• Plethysmography generally refers to the measurement of volume changes of an organ or a body part and in particular to the detection of volume changes due to a cardio -vascular pulse wave traveling through the body of a subject with every heartbeat.
• Photoplethysmography is an optical measurement technique that evaluates a time- variant change of light reflectance or transmission of an area or volume of interest.
• PPG is based on the principle that blood absorbs light more than surrounding tissue, so variations in blood volume with every heart beat affect transmission or reflectance correspondingly.
• a PPG waveform can comprise information attributable to further physiological phenomena such as the respiration.
• a typical pulse oximeter comprises a red LED and an infrared LED as light sources and one photodiode for detecting light that has been transmitted through patient tissue.
• Commercially available pulse oximeters quickly switch between measurements at a red and an infrared wavelength and thereby measure the transmittance of the same area or volume of tissue at two different wavelengths. This is referred to as time-division-multiplexing. The transmittance over time at each wavelength gives the PPG waveforms for red and infrared wavelengths.
• Remote PPG utilizes light sources or, in general radiation sources, disposed remotely from the subject of interest.
• a detector e.g., a camera or a photo detector
• a detector can be disposed remotely from the subject of interest. Therefore, remote photoplethysmographic systems and devices are considered unobtrusive and well suited for medical as well as non-medical everyday applications. This technology particularly has distinct advantages for patients with extreme skin sensitivity requiring vital signs monitoring such as NICU patients with extremely fragile skin or premature babies.
• Verkruysse et al "Remote plethysmographic imaging using ambient light", Optics Express, 16(26), 22 December 2008, pp. 21434-21445 demonstrates that
• photoplethysmographic signals can be measured remotely using ambient light and a conventional consumer level video camera, using red, green and blue color channels.
• the system comprises a monochrome CMOS-camera and a light source with LEDs of three different wavelengths.
• the camera sequentially acquires three movies of the subject at the three different wavelengths.
• the pulse rate can be determined from a movie at a single wavelength, whereas at least two movies at different wavelengths are required for determining the oxygen saturation.
• the measurements are performed in a darkroom, using only one wavelength at a time.
• WO 01/15597 Al discloses an imaging apparatus for representing an image of concentration ratios between a first and a second substance in a region of interest of an object, with different measuring values being represented with different colors and/or gray shades.
• the apparatus comprises a light source capable of irradiating the object with light, which light comprises at least three wavelengths ⁇ , ⁇ 2 and ⁇ 3 , ⁇ 3 being an isobestic wavelength, ⁇ being a wavelength at which the first substance has a lower absorption than the second substance, and ⁇ 2 being a wavelength at which the first substance has a higher absorption than the second substance.
• the apparatus further comprises detection means comprising a matrix of pixel detectors, for representing a virtually instantaneous image of the region of interest.
• US 7,738,935 Bl discloses methods and devices for reduction of motion- induced noise in pulse oximetry when measuring blood oxygen saturation.
• a portion of the light having the first wavelength, a portion oflight having the second wavelength and a portion of the light having the third wavelength are received.
• a first signal is produced based on the received portion of light having the first wavelength.
• a second signal is produced based on the received portion of light having the second wavelength, and a third signal is produced based on the received portion of light having the third wavelength.
• a difference between the second signal and the first signal is determined, wherein the difference signal is first plethysmography signal.
• a difference is determined between the third signal and the first signal to produce a second plethysmography signal. Blood oxygen saturation is then estimated using the first and second plethysmography signals.
• a device for determining the concentration of a substance in the blood of a subject comprising
• an input unit for receiving detection signals reflected back or transmitted through a skin area of the subject in response to irradiation of the skin area by a radiation signal
• a signal extraction unit for extracting at least three photo-plethysmography, PPG, signals at different wavelengths from said detection signals
• a processing unit for normalizing said at least three PPG signals and forming a first difference signal between a first normalized PPG signal and a second normalized PPG signal and a second difference signal between a third normalized PPG signal and one other of the at least three normalized PPG signals and for forming a ratio between said first difference signal and said second difference signal, and
• a concentration detection unit for calculating the concentration of a substance in the blood of the subject based on said ratio.
• a radiation detection unit for detecting detection signals reflected back or transmitted through a skin area of the subject in response to irradiation of the skin area by a radiation signal, and a device as disclosed herein for determining the concentration of a substance in the blood of the subject from said detection signals.
• a computer program which comprises program code means for causing a computer to perform the steps of the method disclosed herein when said computer program is carried out on a computer as well as a non-transitory computer-readable recording medium that stores therein a computer program product, which, when executed by a processor, causes the method disclosed herein to be performed.
• the present invention is based on the idea to use an additional wavelength channel compared to known devices and methods for determining the concentration of a substance like Sp02, which use two wavelength channels. From these at least three wavelength channels difference signals are computed, from which a ratio -of ratio is computed. This can completely remove the effect of specular reflectance and lead to a situation where the use of polarizers, as conventionally used for correct calibration, is no longer necessary. Alternatively or additionally, using the third wavelength channel, the influence of motion can be eliminated from the ratio-of ratios. A greatly enhanced motion robustness is obtained, while the technology can be used for both contact and remote Sp02 measurement systems.
• said processing unit is configured to normalize said PPG signals, in particular by (individually) dividing the PPG signals by their respective temporal means (DC), before forming said difference signals.
• DC temporal means
• said signal extraction unit is configured to extract two PPG signals at two wavelengths of infrared light the first and third PPG signals and one wavelength of visible or infrared light from said detection signals.
• said signal extraction unit is preferably configured to extract a first PPG signal at a first wavelength in the range from 780 nm to 850 nm, a second PPG signal at a second wavelength in the range from 550 to 780 nm and a third PPG signal at a third wavelength in the range from 840 nm to 1000 nm.
• Practical examples are 810 nm for the first wavelength, a wavelength between 840 and 1000 nm as third wavelength and 650 nm (or, if it shall also be invisible, between 700 and 780nm) as second wavelength.
• the same or other wavelengths may be appropriate, wherein preferably at least one wavelength is between 400 and 500 nm for bilirubin detection.
• the two PPG signals at two wavelengths of infrared light represent the first and third PPG signals and the PPG signal at the wavelength of visible or infrared light represents the second PPG signal
• said processing unit is preferably configured to form the first difference signal by subtracting the second normalized PPG signal from the first normalized PPG signal, to form the second difference signal by subtracting the first normalized PPG signal from the third normalized PPG signal and to form said ratio (i.e. the ratio-of-ratios) by dividing said first difference signal by said second difference signal.
• said ratio i.e. the ratio-of-ratios
• the numerator With three wavelengths it is preferred to have in the numerator the highest sensitivity to the substance (e.g. Sp02), i.e. to take the difference between 650 nm (the near visible wavelength) and the longest wavelength (between 840 and 1000 nm).
• the denominator it is preferred to have a low sensitivity to the substance and a difference that never becomes zero. It should be noted, however, that the opposite also works fine, i.e. low sensitivity in the numerator and high sensitivity in the denominator. Sensitivity in both numerator and denominator may also be lead to acceptable results, particularly if they trend in opposite sense (increase in one while decrease in the other). The only case that may not work is when they have an equal sensitivity to the substance.
• a good choice (with three wavelengths) is the difference between 800 and 840 to 1000 nm.
• a somewhat attractive choice for the denominator is to build a weighted sum of all three wavelengths with coefficients that sum up to zero, selected such that there is no sensitivity to the substance. For example, the following equation may be used for
• infrared and the number behind “IR” means the wavelength.
• the advantage is that Sp02 is now linearly related to the ratio. Generally, a linear relation is not required, since it is generally possible to correct for non-linearities.
• said concentration detection unit is configured to calculate the concentration of a substance in the blood by multiplying said ratio with a second calibration parameter and subtracting the result of said multiplication from a first calibration parameter.
• Said calibration parameters are generally constants, which are preferably obtained experimentally.
• An alternative is to use a look-up table to translate the ratio to the concentration of the substance. This is particularly recommended if the relation is non- linear.
• said detection signals are either sensor signals of a contact PPG sensor contacting said skin area of the subject or images of at least said skin area of the subject obtained by an imaging unit, in particular a white-balanced imaging unit.
• an imaging unit in particular a white-balanced imaging unit.
• a white-balanced imaging unit e.g. a white-balanced camera
• white-balancing is only required in case the PPG signals are not normalized before forming the difference signals, as proposed in another embodiment.
• said radiation detection unit preferably either comprises a contact PPG sensor configured to contact said skin area of the subject for detecting sensor signals as detection signals or comprises an imaging unit, in particular a white-balanced imaging unit, for obtaining images of at least said skin area of the subject as detection signals.
• said processing unit is configured to form the ratio between estimated AC amplitudes, in particular e.g. the standard deviation or a more robust amplitude estimate, of said first difference signal and said second difference signal.
• estimated AC amplitudes in particular e.g. the standard deviation or a more robust amplitude estimate
• the ratio of the estimated AC amplitudes in the two difference signals is used, e.g. the ratio of the standard deviation (or a more robust amplitude estimate, like a median of peak-minus- valley- values, or yet another estimate) of the difference signals.
• Fig. 1 shows a schematic diagram of a first embodiment of a system and device for determining the concentration of a substance in the blood of a subject
• Fig. 2 shows a diagram illustrating the effect of specular reflectance
• Fig. 3 shows a diagram of the PPG amplitude for various values of Sp02 over wavelength
• Fig. 4 shows a schematic diagram of a device according to the present invention
• Fig. 5 shows simulation results of Sp02 measurement in a first simulation with two and three wavelengths in a static subject
• Fig. 6 shows simulation results of Sp02 measurement in a first simulation with two and three wavelengths with varying amounts of simulated motion
• Fig. 7 shows simulation results of Sp02 measurement in a second simulation with different systems in a static subject
• Fig. 8 shows simulation results of Sp02 measurement in a second simulation with motion of the subject
• Fig. 9 shows a schematic diagram of a second embodiment of a system and device for determining the oxygen saturation of a subject.
• Fig. 1 shows a schematic diagram of a first embodiment of a system 1 and device 10 for determining the concentration of a substance in the blood of a subject 2.
• the invention shall be explained by determining the oxygen saturation (Sp02) in the subject's blood.
• Sp02 oxygen saturation
• the subject 2 in this example is a patient lying in a bed 3, e.g. in a hospital or other healthcare facility, but may also be a neonate or premature infant, e.g. lying in an incubator, or person at home or in a different environment.
• the system 1 generally comprises a radiation detection unit for detecting detection signals reflected back or transmitted through a skin area 4 of the subject 2 in response to irradiation of the skin area 4 by a radiation signal.
• the radiation detection unit is an imaging unit 20, in particular a camera (also referred to as detection unit or as camera-based or remote PPG sensor), for obtaining images of at least said skin area 4 of the subject 2 as detection signals.
• the skin area 4 is preferably an area of the face, such as the cheeks or the forehead, but may also be another area of the body, such as the hands or the arms.
• the radiation signal in this example is the ambient light, e.g. as provided by the sun and/or from room lighting.
• special light source(s) are provided for illuminating the subject 2 or at least the skin area 4 of the subject 2 with radiation of particular wavelength(s) and/or (only) at times of measurement (e.g. during night time).
• the image frames captured by the camera may particularly correspond to a video sequence captured by means of an analog or digital photosensor, e.g. in a (digital) camera.
• a camera usually includes a photosensor, such as a CMOS or CCD sensor, which may also operate in a specific spectral range (visible, IR) or provide information for different spectral ranges.
• the camera may provide an analog or digital signal.
• the image frames include a plurality of image pixels having associated pixel values. Particularly, the image frames include pixels representing light intensity values captured with different photosensitive elements of a photosensor. These photosensitive elements may be sensitive in a specific spectral range (i.e. representing a specific color).
• the image frames include at least some image pixels being representative of a skin portion of the subject.
• an image pixel may correspond to one photosensitive element of a photo-detector and its (analog or digital) output or may be determined based on a combination (e.g. through binning) of a plurality of the photosensitive elements.
• the obtained detection signals i.e. in this embodiment the sequence of images, are provided to the device 10 for further processing that will be explained below in more detail.
• While such a system can generally be used for obtaining various vital signs by use of the known remote PPG technology, it is used according to the present invention for determining the oxygen saturation of arterial blood (also referred to as Sp02) within the subject 2.
• the light reflected back from the skin of the subject is modulated by the pulsatile arteries and the modulation amplitude contains the information of the blood saturation levels.
• Sp02 is computed by measuring this PPG amplitude (caused by pulsatile blood in arteries) at two distinct wavelengths. The ratio between the PPG amplitudes (DC normalized) of the two wavelengths gives the equation 1 for the computation of Sp02:
• Calibration refers to inter-person and intra-person calibration leading to incorrect Sp02 measurements and errors can be caused due to a number of factors.
• One of these causes has been found to be subject motion, which leads to motion- induced intensity variations in addition to the intensity variations due to PPG.
• Another one of these causes has been found to be specular reflectance, the mirror like reflectance of light of the skin surface, which makes camera Sp02
• the specularly reflected light reaching the camera 20 does not contain any light modulation due to arterial blood pulsatility and hence causes a decrease in relative pulsatility of the total reflected light. Consequently there will be errors in Sp02 measurement depending on the fraction of the specularly reflected light in the total reflected light from the skin.
• Specular reflectance depends on the angles between the camera, the subject and the illumination source and is an additive property adding an equal but unknown amount of DC reflectance across all wavelengths equally as shown in Fig. 2 depicting a curve Kl of the diffuse and specular reflectance and a curve K2 of the diffuse reflectance only, both curves over wavelengths of light.
• the polarizers are attached at the illumination source and the cameras and oriented in such a way that all specularly reflected light is blocked away. Even though this is a generic solution, one key problem lies in the low practicality of this solution.
• the present invention uses an additional wavelength with which the effect of specular reflectance can be removed from the measurement of the Sp02.
• the specular reflection disappears in a difference channel built from two wavelengths, in particular if the camera 20 has been white-balanced, i.e. the light source gives equal signal in both channels corresponding to said wavelengths.
• the conventionally used "red” and “infrared” channels are replaced by two "difference” channels eliminating the influence of specular reflection, while the Sp02 sensitivity remains, provided at least one of these difference channels exhibits a pulsatility that varies with the oxygenation level.
• the calibration constants differ from the ones used in the conventional systems using two wavelengths. Said calibration constants are e.g. established experimentally or through simulation.
• a PPG signal is preferably obtained from a region of interest in a sequence of images, and ⁇ ( ⁇ ) representing an estimate of the amplitude of the AC-component of x, which can be computed in different ways (in an embodiment ⁇ ( ⁇ ) represents the standard deviation of the time varying signal x).
• the camera(s) is preferably white-balanced to ensure specular reflectance is completely removed in the difference signals. This may be obtained by firstly white- balancing the camera setup. Since the wavelengths might not necessarily be in the visible range a calibration surface capable of reflecting all wavelengths is preferably used. With this setup and a given illumination the cameras can be white-balanced according to the standard procedure and the DC levels of all the wavelengths equalized.
• the white-balancing holds as long as the illumination has a constant spectral response. Changes in the illumination's spectral response would still be tolerable as long as it is constant across all wavelengths. However, if at any time the spectral response of the illumination changes non-uniformly across the wavelengths, a recalibration is preferably applied for the complete elimination of specular reflection. Without such re-calibration, still an incomplete compensation of the specular reflection would result.
• the calibration constants CI and C2 changes. The computations for these constants would follow the white-balance calibration and be the same as for the conventional Sp02 measurements done with a camera.
• PPG-induced pulsatility is much smaller in the normalized red channel than in the normalized infrared channel for healthy Sp02 levels, although the levels can become close to each other for very low Sp02 values.
• Motion induced intensity variations however, are typically of equal strength in both channels and consequently lead to an under-estimation of the actual Sp02 estimates.
• the index "n" indicates the DC normalization of the respective PPG signal.
• the index "n” indicates the DC normalization of the respective PPG signal.
• three wavelengths are used for this SP02 measurement system.
• the calibration constants differ from the ones used in the conventional system and in the above described embodiment of the present invention and are e.g.
• a first PPG signal is extracted at a first wavelength in the range from 780 nm to 850 nm
• a second PPG signal (R) is extracted at a second wavelength in the range from 550 to 780 nm
• a third PPG signal is extracted third wavelength in the range from 850 nm to 1000 nm.
• An example choice valid for Sp02 uses 660 nm, 810 nm and 870 nm.
• FIG. 4 A schematic diagram of a device 10 for determining the oxygen saturation of the subject 2 is depicted in Fig. 4.
• the device 10 comprises an input unit 11 for receiving detection signals reflected back or transmitted through a skin area of the subject in response to irradiation of the skin area by a radiation signal.
• the detection signals may e.g. be obtained by the imaging unit 20 or a contact PPG sensor as explained below in another embodiment of the system.
• a signal extraction unit 12 extracts at least three photo-plethysmography (PPG) signals at different wavelengths from said detection signals.
• a processing unit 13 forms a first difference signal between a first PPG signal and a second PPG signal and a second difference signal between a third PPG signal and the first PPG signal. Further, the processing unit 13 forms a ratio between said first difference signal and said second difference signal. Based on said ratio an oxygen saturation detection unit 14 calculates the oxygen saturation of the subject.
• PPG photo-plethysmography
• the ratio-of-ratios has been computed, i.e. the basis for Sp02 estimation without the calibration, for the conventional Sp02 measurement with two wavelengths and the proposed motion-robust Sp02 measurement with three wavelengths.
• Fig. 5 shows the simulation results along with the ideal curves obtained in the absence of noise and motion, wherein Fig. 5A shows the result when using two wavelengths and Fig. 5B shows the result when using three wavelengths. These curves are different, reflected by the different angle of the lines, indicating a different calibration. The three wavelengths system is not affected by motion.
• the straight lines in both figures give the ideal ratio-of-ratios, i.e. without noise and motion.
• Fig. 6 shows simulation results of Sp02 measurement with two wavelengths (Fig. 6A) and three wavelengths (Fig. 6B) with varying amounts of simulated motion. Each curve indicates the magnitude of motion w.r.t the maximum signal in the red channel added.
• Curve K3 shows the Sp02 measurement with three channel difference signals
• Curve K4 shows the Sp02 measurement with conventional two channel measurement
• Curve K5 shows the Sp02 measurement with contact reference with Sp02 variation in a static subject.
• a subject in continuous and periodic motion is used to evaluate the performance of the algorithm.
• the calibration constants (CI, C2) used were taken from the previous experiment. The entire recording is divided into multiple sections indicating the amount of motion added (from no motion to very high motion as time increases).
• Fig. 8 shows measurement results.
• curve K6 shows Sp02 measurement with three channel difference signals
• curve K7 shows conventional two channel measurement
• curve K8 shows contact reference with motion of the subject. Significant signal quality degradation can be observed even with a static subject.
• Fig. 9 shows a schematic diagram of a second embodiment of a system 1 ' and device 10' for determining the oxygen saturation of a subject 2.
• a contact PPG sensor 21 is provided instead of an imaging unit (20 in Fig. 1) .
• Such a contact PPG sensor 21 is generally known and comprises a light unit and a photosensor.
• Said contact PPG sensor 21 is mounted to the body of the subject 2, e.g. to the arm, finger, nose, earlobe, etc., i.e. is configured to contact said skin area of the subject for detecting sensor signals as detection signals.
• the main application of the present invention is the measurement of contactless Sp02 robust to the presence of specular reflectance and/or motion for patient monitoring applications in the NICU and general ward.
• the present invention is equally applicable for contact vital signs sensors and remote (camera-based) PPG systems, and can also be used to determine the concentration of other substances in the subject's blood, such as C02 or bilirubin.
• a computer program may be stored/distributed on a suitable non-transitory medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.
• a suitable non-transitory medium such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.

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• 2015
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