WO2007097702A1 - surveillance non invasive d'écoulement sanguin dans les tissus profonds - Google Patents

surveillance non invasive d'écoulement sanguin dans les tissus profonds Download PDF

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Publication number
WO2007097702A1
WO2007097702A1 PCT/SE2007/050101 SE2007050101W WO2007097702A1 WO 2007097702 A1 WO2007097702 A1 WO 2007097702A1 SE 2007050101 W SE2007050101 W SE 2007050101W WO 2007097702 A1 WO2007097702 A1 WO 2007097702A1
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Prior art keywords
blood
blood flow
ppg
blue
vessels
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PCT/SE2007/050101
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English (en)
Inventor
Lars-Göran LINDBERG
Jan NÄSLUND
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Lindberg Lars-Goeran
Naeslund Jan
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Publication of WO2007097702A1 publication Critical patent/WO2007097702A1/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
    • 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
    • A61B5/024—Detecting, measuring or recording pulse rate or heart rate
    • A61B5/02416—Detecting, measuring or recording pulse rate or heart rate using photoplethysmograph signals, e.g. generated by infrared radiation
    • A61B5/02427—Details of sensor
    • A61B5/02433—Details of sensor for infrared radiation
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4738—Diffuse reflection, e.g. also for testing fluids, fibrous materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4504—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4519—Muscles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4528—Joints
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light

Definitions

  • the current invention relates to the field of monitoring and measuring blood volume and blood flow in deep tissues, such as bone and dental pulp but also in muscle and other tissue, non-invasively. Measurements of blood volume, blood pressure and blood flow can be carried out at rest or during functional or physical activities and enable associated conditions and disease status to be assessed, subsequently enabling the need for treatment to be assessed and appropriate therapy regimes to be applied.
  • Photoplethysmography is a non-invasive optical technique for assessing blood flow-related phenomena which has mainly previously been used to assess blood perfusion in skin (Kamal et al. 1989). It has also been used for measuring muscle blood flow (Sandberg et al., 2005; Zhang et al., 2001). Recently, the technique has also been used to study the effects of sensory stimulation on blood flow in muscle tissue (Sandberg et al., 2004).
  • the present invention relates to a novel method for monitoring and measuring blood characteristics, such as blood flow in deep tissue, for example in bone, by establishing that changes in blood flow can be monitored in a rigid blood conduit, or in blood vessels of limited flexibility.
  • blood vessels include the vascular system in trabecular bone, vascular tissue in muscle (where one utility of the present invention is the ability to assess changes in blood flow while the subject is in motion) and vascular cells which have lost flexibility, for example in diseases such as arteriosclerosis.
  • the motility characteristics of red blood cells (RBCs) in circular conduits are exploited by the present invention, in particular the orientation of RBCs and their axial migration and corresponding light absorption and reflection in order to give rise to an AC (alternating current ) and DC (direct current) components of a novel PPG signal.
  • the PPG A c signal allows the monitoring of rapid changes in blood characteristics while the PPG D c signal allows monitoring of slow variations.
  • Each of the individual signal components can be separated by appropriate filters.
  • a novel photoplethysmographic (PPG) technique is used to assess blood flow in bone tissue.
  • a novel PPG probe is applied non- invasively to the skin overlying the bone containing the vessels to be analysed.
  • the novel probe uses near-infrared and green wavelength light sources (in the case, for example of measurement of blood flow in the patella, wavelengths of 804 nm and 560 nm respectively are used) and the AC component of the PPG signals of the two wave-lengths are used to non-invasively monitor pulsatile blood flow characteristics in the bone tissue and in the overlying skin respectively.
  • blood flow in terms of volume of blood per unit of time, blood pressure (and blood pressure variations) as well as pulsatile blood volume can be monitored.
  • Additional blood characteristics which can be monitored are hematokrit, hemoglobin concentration, oxygen content, oxygen saturation, blood viscosity properties and vessel compliance (wall extensibility).
  • the novel PPG technique is used to assess the flow of blood in vessels of soft tissues, for example in vessels such as the radial artery and vessels in the muscle compartment.
  • novel PPG technique is used to monitor and measure the flow of blood in rigid-like vessels, or in vessels of limited flexibility having an inner diameter equal to or greater than 2 mm.
  • novel PPG technique is used to determine blood flow in rigid vessels, or in vessels of limited flexibility, having an inner diameter of less than 2 mm.
  • FIG. 1 shows the underside of a photoplethysmography (PPG) probe.
  • the probe comprises in this instance three light sources (one red light-emitting diode and two green light-emitting diodes (LEDs)) and a photodetector (PD).
  • the probe dimensions are 50 mm x 38 mm.
  • Figure 2 shows a schematic representation of photon (light) distribution during photoplethysmography of the patella.
  • the dark section represents patellar bone, the white area is soft tissue.
  • PD photodetector
  • LEDs light-emitting diodes
  • the upper curve trace shows the PPG signal as most often presented on a display or a computer screen.
  • the lower curve trace is the original PPG signal detected with a photodetector placed adjacent to the light source or placed opposite to the light source.
  • Figure 3b shows data mining in order to determine the derived physiological parameters and/or characteristics from the PPG A c signal. From the amplitude of the PPG A c signal (PPG 3 ) changes in blood pressure can be derived, from the slope (PPG S ⁇ O p ⁇ ) blood velocity can be derived and from the area under the curve (PPG auc ) the pulsatile blood volume can be derived. The measurement derivations can be rapidly computed and registered.
  • Figure 4 shows a typical photoplethysmographic recording from bone (804 nm) and skin (560 nm) in one subject at rest.
  • the PPG signals are in arbitrary units. Note the difference in baseline between the two curves; the slow-wave shift at 560 nm may reflect autoregulator ⁇ activity in the skin whereas such activity is not evident in the recording at 804 nm.
  • FIG 6a shows the AC component of a photoplethysmographic signal (PPG A c) as a function of the pulsatile blood pressure in a hydraulic model.
  • PPG A c photoplethysmographic signal
  • the PPG signal is obtained in reflexion mode from a rigid, transparent circular tube, where the flow varies in proportion to the pressure ( Figure 6b).
  • Mean blood flow (Q) is shown as a function of pulsatile blood pressure.
  • Figure 7 shows a schematic illustration of the RBC distribution in a circular conduit during the systolic and diastolic phase of the cardiac cycle and how the photons are reflected at a theoretical image boundary between the plasma layer and the RBCs.
  • Figure 8 shows a schematic illustration of the signal generation of the PPG A c signal according to a) the blood volume theory and b) the concept of the present invention of migration and orientation of RBCs during the cardiac cycle.
  • Figure 9 shows comparisons of typical recordings over the radial artery using the novel PPG signal generation and detection of the present invention compared to measurements made on the finger using Portapres for the continuous measurement of blood pressure.
  • BS bone scintigraphy
  • SPECT single-photon emission computed tomography
  • PDT position emission tomography
  • LDF Laser- Doppler flowmetry
  • NIRS Near infrared spectroscopy
  • the PPG technique in reflection mode requires a light source and a photodetector (PD) placed adjacent to each other.
  • the beam of light is directed toward the part of tissue in which blood flow is to be measured.
  • the emitted light is reflected, absorbed, and scattered within the tissue, and only a small fraction of the emitted light is received by the PD.
  • the intensity of the reflected and scattered light is recorded by the PD and assumed to be related to blood flow changes occurring underneath the probe (Lindberg and ⁇ berg, 1991).
  • the depth to which light penetrates a tissue is primarily a function of wavelength and the optical geometry of the probe but also of the optical qualities of the tissues of interest.
  • the electrical signal detected by the photoplethysmograph consists of a steady component (DC) — which is related to the relative vascularization of the tissue— and a pulsatile component (AC)- which is synchronous with the pumping action of the heart.
  • DC steady component
  • AC pulsatile component
  • the amplitude of the heart-synchronous AC component is thought to be correlated to the blood flow under the probe (Kamal et al., 1989). It has mostly been suggested that the AC component is related to pulsatile volume changes due to varying lumen of the vessel (Challoner, 1979).
  • At least one light source emitting light of near- infrared, using a wavelength of from 600-1300 nm, in conjunction with at least one pair of blue-green light-emitting sources, for example LEDs (using a wavelength of from 430-600 nm) and a photo-detector (PD), the monitoring and measurement of blood flow in rigid blood vessels or in vessels of limited flexibility can be carried out continuously, accurately and reproducibly.
  • at least one light source emitting light of near- infrared
  • at least one pair of blue-green light-emitting sources for example LEDs (using a wavelength of from 430-600 nm) and a photo-detector (PD)
  • a near-infrared wavelength of 804 nm is used.
  • an infrared-emitting light source suitably a LED is placed 25 mm from a photo-detector (PD), in conjunction with two green light sources emitting light of 560 nm
  • PD photo-detector
  • a typical novel PPG signal is schematically presented in Figure 3a.
  • the lower curve trace is the original one, with a negative deflection corresponding to systole and a positive deflection corresponding to diastole.
  • the upper curve trace is the normally presented signal on e.g. a display, so that the positive deflection (the peak) of the PPG signal or PPG 3 is synchronous with the peak of the pressure curve recorded invasively.
  • An example of how novel parameters can be derived from the PPG signal is illustrated in Figure 3b. A range of different physiological parameters can be derived, based on the new concept for the generation of the PPG signal.
  • PPG 3 is directly proportional to pulsatile pressure variations and can be converted to readings of increase or lowering of blood pressure or systolic pressure in mm Hg.
  • the PPG S ⁇ O p ⁇ is partially proportional to the maximum velocity of RBCs or rate of blood flow and the pulsatile blood volume can be monitored derived from the data obtained from the area under the curve (PPG auc )-
  • PPG auc area under the curve
  • PPG 3 is proportional to variations in pulsatile pressure and systolic blood pressure
  • PPGsiope is proportional to variations in maximum pulse velocity
  • PPGauc is proportional to variations in blood volume of each pulse
  • PPG DC is not shown in the figure, but changes slowly over time and is proportional to blood volume.
  • the light source or multiple sources, emitting light of near-infrared wavelength can be placed within a distance interval of 5 mm to 50 mm of the detector.
  • the near-infrared light source can be used in conjunction with the light sources emitting green-light wavelengths when these light sources are located within distance intervals of 0 mm to 5 mm of the detector.
  • blood flow variations are monitored in bone fracture patients for the purposes of diagnostics and prognostics during treatment, utilizing the novel PPG probe to assess blood flow changes before, during and after bone fracture.
  • the novel PPG probe is used to assess the effect on blood flow in cases of bone growth in health and disease, in processes where the bone tissue is growing both in healthy subjects and in patients where the bone growth is affected for different reasons.
  • An illustrative example of this utility of the invention is the monitoring of bone growth during physical exercise in athletes during athletics training and competition and during rehabilitation following stress or injury.
  • blood flow characteristics and variations are monitored using the novel PPG probe in cases of hip fracture in elderly patients for screening for selection of treatment modalities.
  • blood flow, blood characteristics and variations are monitored for the purpose of diagnostics and follow-up in osteopenia, osteoporosis (OP) and osteoarthritis (OA) patients before and after surgery.
  • Yet a further embodiment of the present invention is the assessment of blood flow in atherosclerotic vessels.
  • the novel PPG probe is used to assess the effect of rigid vessel walls on blood flow by assessing the difference between blood flow related parameters in normal vessels and in atherosclerotic vessels.
  • Another embodiment of the present invention is the use of the novel PPG probe in the assessment of blood flow in connective tissues.
  • the present invention can be used to compare the pattern of pulsatile blood flow in individual patients before and after an intervention, or analysis of movement.
  • the present invention can also be used to assess possible differences between patients and controls in a variety of deep tissues without knowing the rate of blood flow, which enables the invention to be used in continuing research into the underlying characteristics of various diseases, conditions and mechanical injury.
  • the importance of using a non-invasive instrument for measuring blood flow in a variety of instances is clear and is exemplified by a number of studies on knee surgery where disruption of the vessels supplying the patella, for example, has been shown to occur after lateral release and anterior cruciate ligament reconstruction with bone-tendon-bone autografts (Bonutti et al; 1998).
  • the novel PPG probe (see Figure 1) was placed over the centre of the patella bone and attached to the skin with adhesive tape. After 15 min of rest, blood flow was recorded continuously from 60 s before the intervention to 5 min after. Blood flow was measured with the knee fixed (by means of a vacuum pillow, AB Germa, Sweden) in a position at 20° of flexion during all interventions. The PPG signal was analyzed by an investigator who was blinded to the subjects and recording conditions. Various procedures were used to influence the blood flow superficially in the skin or in the patella bone. The nature and purpose of the interventions are described in more detail below.
  • Transvasin® Liniment
  • the active substances in Transvasin® tetrahydrofurfursalicylate, ethyl nicotinate and hexylnicotinate
  • nicotinic acid has a dilating effect after a few minutes (Sandberg et al., 2004).
  • PPG recordings were performed for 60 s to establish a reference value. The probe was then moved, and a minor amount of liniment was quickly applied to the surface of the PD. After replacing the probe at the same site on the patella, blood flow was measured for another 5 min.
  • the purpose of this experiment was to investigate the ability of the PPG instrument to differentiate between skin and bone blood flow when a substance known to induce skin vasodilatation was applied to the skin. For results see section 1.6 below and Figure 5d.
  • Figure 4 shows a typical PPG recording from bone (804nm) and skin (560nm) at rest in one subject. There was a slow variation in baseline of the skin PPG signal but not in the corresponding signal from bone tissue. The amplitudes of the AC component during the interventions are presented in Figure 5a-d. Values are expressed as percent of pre- intervention control. In the results, the mean values from the left and right knees are presented. Some recordings of the PPG signal were not analyzed due to 50 Hz noise and in such instances only the recordings from one knee were analysed. In some interventions, fewer than 20 subjects were analyzed, also because of high noise in the PPG signal.
  • FIG. 5a vascular occlusion of skin tissue is shown in Figure 5a.
  • the PPG signal from the skin over the patella (560 nm) was blocked after application of a local pressure of 100 mm Hg.
  • the rigid flow-through model consisted of a hole (diameter 2 mm) drilled in a piece of acrylic glass (PMMA).
  • a LED (wavelength 880 nm) was used as the light source for the illuminating fibre.
  • the light from the detecting fibre was guided to a silicon PD (CERLED, Germany).
  • the measurements were performed on blood from 12 healthy blood donors, with Hb concentrations ranging from 116-162 g/l.
  • the blood was circulating in a silicon tubing system described earlier (Lindberg and Oberg, 1993).
  • a waveform generator regulated a roller pump (Mekaneljo, Sweden), which produced a simulated pressure waveform closely resembling the human pulsatile blood pressure (Lindberg and Oberg, 1993; Borgstr ⁇ m, 1981).
  • Blood flow in ml/min was determined by collecting the blood for 60s at each pressure level. Measurements were made with both whole blood and hemolyzed blood.
  • Figure 6a shows relative changes in the PPG AC signal when the pulsatile pressure was varied between 0 and 100 mm Hg, superimposed on a constant diastolic pressure of 70 mm Hg and at a constant frequency of 1 Hz (corresponding to 60 beats/min).
  • Figure 6b shows that the blood flow (ml/min) through the rigid tube varied linearly with the intra-tube pressure.
  • the experiments were performed using both whole- and hemolyzed blood from the same donors. With whole blood the PPG AC-signal varied with the pressure pulse. Plotting the values from PPG AC-recordings against the pulsatile pressure, the correlation coefficient was 0.82. With hemolyzed blood no pulsatile signals were recorded.
  • EXAMPLE 3 shows relative changes in the PPG AC signal when the pulsatile pressure was varied between 0 and 100 mm Hg, superimposed on a constant diastolic pressure of 70 mm Hg and at a constant frequency of 1 Hz (corresponding to 60 beats/min).
  • PFPS patellofemoralpain syndrome
  • the novel PPG signal generation of the present invention is schematically illustrated in Figure 7 by the relationship between the core of red blood cells (RBCs) and the majority of the plasma layer in a cross section of a circular rigid tube (no pulsatile volume changes because there is no variation in the lumen/diameter of the tube (vessel)).
  • RBCs red blood cells
  • the theoretical image boundary plasma layer is thicker and in the diastolic phase it is thinner.
  • Light reflection in plasma is also lower compared to reflection in solute containing RBCs.
  • the increased distance and the thicker plasma layer reduces the amount of light reflected back towards a photodetector and during diastole the decreased distance and the thinner plasma layer increases the light reflected back. All this taken together explains the origin and the phase of the PPG A c signal shown diagramatically in the upper trace curves of the figure.
  • Recordings in accordance with Figure 9 over a vessel of diameter approximately ⁇ 2mm resembling a rigid vessel may be performed on a variety of vascular beds and for different applications.
  • the degree of atherosclerosis of a vessel may be determined by frequency analysis of the PPG signal based on our novel concept where the orientation/migration of RBCs are distorted in a specific way. Similar signal analysis may be used for determination of stiff vascular walls.
  • Hemodynamic instability is a common complication during dialysis treatment and has been postulated to result from intravascular fluid loss and the inability of the cardiovascular system to compensate for this, leading in turn to hypotension and reduction in the effectiveness of dialysis treatment.
  • Using the PPG signal generation and detection method of the present invention we can measure and periodically or continuously monitor the hemodynamic status of an individual before, during and after dialysis, both using direct PPG signals and derived measurements. In the measurements and monitoring of dialysis patients two monitoring devices are used; one placed over the radial artery and one placed over the muscles of the underarm.

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Abstract

L'invention concerne un procédé de génération, détection et évaluation d'un signal photoplethysmographique (PPG) pour surveiller les caractéristiques sanguines dans les vaisseaux sanguins de flexibilité réduite, comme dans les compartiments vasculaires et les vaisseaux de tissus profonds. L'invention se base sur les effets que l'orientation et la migration axiale de globules rouges ont sur l'absorption, la dispersion et la réflexion de la lumière (photons) de longueur d'onde proche de l'infrarouge et de longueur d'onde bleue verte. Dans l'invention, la ou les sources de lumière de longueur d'onde proche de l'infrarouge et la ou les sources de lumière de longueur d'onde bleue verte sont espacées selon des distances particulières par rapport à un ou plusieurs photodétecteurs. Ce procédé permet la surveillance continue, non invasive de caractéristiques sanguines et des changements de ces caractéristiques avec le temps. Les données obtenues par ce procédé comportent la pression sanguine, l'écoulement sanguin, le volume de sang pulsé et la vitesse des globules rouges dans les vaisseaux sanguins qui sont rigides ou qui ont une flexibilité réduite, comme le tissu vasculaire osseux ou dans les vaisseaux athéroscléreux ou tendus.
PCT/SE2007/050101 2006-02-21 2007-02-21 surveillance non invasive d'écoulement sanguin dans les tissus profonds WO2007097702A1 (fr)

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US20110282219A1 (en) * 2008-12-05 2011-11-17 Atys Sarl Measurement of systolic pressure
WO2012110955A1 (fr) 2011-02-14 2012-08-23 Reuven Gladshtein Indications fournies par la section des petits vaisseaux sanguins ramifiés
CN102940494A (zh) * 2012-10-18 2013-02-27 北京超思电子技术股份有限公司 可测量体温的血氧测量仪
US8521247B2 (en) 2010-12-29 2013-08-27 Covidien Lp Certification apparatus and method for a medical device computer
WO2014018831A1 (fr) * 2012-07-26 2014-01-30 Vivonics, Inc. Système et procédé de détermination d'une mesure de la résistance du système vasculaire périphérique
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WO2014124520A1 (fr) * 2013-02-13 2014-08-21 Mespere Lifesciences Inc. Procédé et dispositif pour mesurer l'oxygénation du sang veineux
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GB2522298A (en) * 2013-10-17 2015-07-22 Univ Loughborough Opto-physiological sensor and method of assembly
EP2939593A1 (fr) 2014-05-02 2015-11-04 Lindberg, Lars-Göran Dispositif et système pour déterminer des paramètres physiologiques à partir de l'os du sternum
CN105310697A (zh) * 2014-07-28 2016-02-10 深圳先进技术研究院 测量血氧饱和度的方法及装置
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JP2017018569A (ja) * 2015-07-07 2017-01-26 三星電子株式会社Ｓａｍｓｕｎｇ Ｅｌｅｃｔｒｏｎｉｃｓ Ｃｏ．，Ｌｔｄ． 生体信号測定装置及び方法
US20170128024A1 (en) * 2014-07-28 2017-05-11 Koninklijke Philips N.V. Heart rate monitor system and method of determining a warming-up status of a user
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