(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY(PCT)
`
`CX-1703
`
`(19) World Intellectual Property Organization
`International Bureau
`
`
`
`(10) International Publication Number
`(43) International Publication Date
`WO 03/068060 Al
`21 August 2003 (21.08.2003)
`PCT
`
`(51) International Patent Classification’:
`
`A6IB 5/00
`
`{81} Designated States national): AE, AG, AL,AM, AP, AU,
`AZ, BA, BR, BG, BR, BY, BY, CA, CTI, CN, CO, CR, CU,
`CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH,
`@1) Taternatioual Application Number:|PCT/FTO3/00089
`GM, HR, HU, 0D, 0. IN, 1S, JP, KE, KG, KP, RR, KZ, LC,
`LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW,
`MX, MZ, NO, NZ. OM, PH, PL, PT, RO, RU, SC, SD, SE,
`SG, SK, SL, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ,
`VC, VN, YU, ZA, ZM, ZW.
`
`(22) Nuternational Filing Date: 4 february 2003 (04.02.2003)
`
`(25) Filing Language:
`
`English
`
`(26) Publication Language:
`
`English
`
`(30) Priority Data:
`10/077 ,196
`
`15 February 2002 (15.02.2002)
`
`US
`
`(71) Applicant (for ail designated Staies except US); DATEX-
`OHMEDA,INC. [US/US]; 3030 Ohmeda Drive, Madison,
`WI 53707 (US).
`
`(72) Inventor; and
`(75) Tnventor/Applicant (or US only): HUBSU, Matti (FFU;
`Kaksoiskiventie 30 H, FEN-02760 Espoo (FD.
`
`PATENT AGENCY COMPATENT LYD.,
`(74) Agent:
`Hiimeentie 29, 4th Floor, FIN-00500 Helsinki (FD.
`
`(84) Designated States (regional): ARIPO patent (GH, GM,
`KH, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZM, ZW),
`Eurasian patent (AM, AZ, BY, KG, K7%, MD, RU, TJ,TM),
`Burepean patent (AT, BE, BG, CH, CY, CZ, DE, DK, TE,
`US, UL UR, GB, GR, HU, LW, 11, LU, MC, NL, PT, SL, SI,
`
`SK, TR), OAPI patent (BF, BY, CR, CG, CT, CM, GA, GN,
`GQ, GW, ML. MR, NE, SN, TD, TG).
`
`Published:
`with international search report
`
`For two-letter codes and other abbreviations, refer to the “Guid-
`ance Noies on Codes andAbbreviations" appearing at the begin-
`ning ofcach regular issue efthe PCT Gazette.
`
`(54) Title: COMPENSATION OF HUMAN VARIABILITY IN PULSE OXIMETRY
`
`_
`
`PERFORM INITIALCHARACTERIZATION
`MEASUREMENTS
`
`| ESTABLISH NOMINAL CHARACTERISTICS
`
` i
`| DESCRIBING CALIBRATION CONDITIONS
`
`STORE REFERENCE CATA INDICATING
`CALIBRATION CONDITIONS
`
`
`
`PERFORM IN-VIVO MEASUREMENTS ANDDETERMINE
`
`TISSUE-INDUCED CHANGESIN NOMINAL CHARACTERISTICS
`
`
`BASED ON TISSUE-INDUGED CHANGES,
`DETERMINE SUBJECT-SPECIFIC CALIBRATION FOR PULSE OXIMETER
`
`(87) Abstract: The inventionrelates to the calibration ofa pulse oximeter intended for non-invasively determining the amountofat
`Jeast twolight-absorbing substances in the blood of a subject. In order to bring about a solution by means of whichthe effects caused
`bythe tissue of the subject can be taken into account in connection with the calibration of a pulse oximeter, initial characterization
`measurements are carried out for a pulse oximeter calibrated under nominal conditions. Based on the characterization measurements,
`nominal characteristics are established describing the conditions under which nominal calibration has been defined, and reference
`data indicating the nominal characteristics are stored. In-vivo measurements are then performed on living tissue and based on the
`in-vivo measurements and the reference data stored, tissue-induced changes in the nominal characteristics are determined. Subject-
`specific variation in the in-vivo measurements is compensated for by correcting the nominal calibration on the basis ofthe tissue-
`induced changes.
`
`O03/068060Al
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`3
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`APL_MAS_ITC_00304255
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`MASIMO2067
`Apple v. Masimo
`IPR2022-01299
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
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`WO 03/068060
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`PCT/FI03/00089
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`COMPENSATION OF HUMANVARIABILITY IN PULSE OXIMETRY
`
`Field of the Invention
`The invention relates generally to pulse oximeters used to detect
`blood oxygenation. More specifically, the invention relates to a method for
`taking into account human variability in pulse oximeters. The invention further
`relates to a sensor allowing compensation for the inaccuracies caused by
`humanvariability, the sensor being an integral part of the pulse oximeter.
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`Background of the Invention
`Pulse oximetry is at present the standard of care for continuous
`monitoring of arterial oxygen saturation (SpOz). Pulse oximeters provide
`instantaneous in-vivo measurements of arterial oxygenation, and thereby an
`early warning of arterial hypoxemia, for example.
`A pulse oximeter comprises a computerized measuring unit and a
`probe attached to the patient, typically to a finger or ear lobe. The probe
`includes a light source for sending an optical signal through the tissue and a
`photo detector for receiving the signal after transmission through the tissue.
`On the basis of the transmitted and received signals, light absorption by the
`tissue can be determined. During each cardiac cycle, light absorption by the
`tissue varies cyclically. During the diastolic phase, absorption is caused by
`venous blood, tissue, bone, and pigments, whereas during the systolic phase
`there is an increase in absorption, which is caused by the influx of arterial
`blood into the tissue. Pulse oximeters focus the measurementon this arterial
`blood portion by determining the difference between the peak absorption
`during the systolic phase and the constant absorption during the diastolic
`phase. Pulse oximetry is thus based on the assumption that the pulsatile
`componentof the absorption is due to arterial blood only.
`Light transmission through an ideal absorbing sample is determined
`by the known Lambert-Beer equation as follows:
`Loy = Ly eee,
`(1 )
`
`fou is the light
`intensity entering the sample,
`where fn is the light
`intensity received from the sample, D is the path length through the sample, ¢
`is
`the extinction coefficient of the analyte in the sample at a specific
`wavelength, and C is the concentration of the analyte. When/,, D, and ¢ are
`known, and Jou: is measured, the concentration C can be calculated.
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`IPR2022-01299
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`CX-1703
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`in order to distinguish between twospecies of
`In pulse oximetry,
`hemoglobin, oxyhemoglobin (HbO2), and deoxyhemogiobin (RHb), absorption
`must be measured at two different wavelengths, [.e. the probe includes two
`different light emitting diodes (LEDs). The wavelength values widely used are
`660 nm (red) and 940 nm (infrared), since the said two species of hemoglobin
`have substantially different absorption values at these wavelengths. Each LED
`is iluminated in turn at a frequency whichis typically several hundred Hz.
`The accuracy of a pulse oximeteris affected by several factors. This
`is discussedbriefly in the following.
`Firstly,
`the dyshemoglobins which do not participate in oxygen
`transport,
`ie. methemoglobin (MetHb) and carboxyhemoglobin (COHDb),
`absorb light at the wavelengths used in the measurement. Pulse oximeters are
`set up to measure oxygen saturation on the assumption that the patient's
`blood composition is the same as that of a healthy, non-smokingindividual.
`Therefore, if these species of hemoglobin are present in higher concentrations
`than normal, a pulse oximeter may display erroneous data.
`Secondly, intravenous dyes used for diagnostic purposes may cause
`considerable deviation in pulse oximeter readings. However, the effect of these
`dyes is short-lived since theliver purifies bloodefficiently.
`Thirdly, coatingslike nail polish may in practice impair the accuracy of
`a pulse oximeter, even though the absorption caused by them is constant, not
`pulsatile, and thus in theory it should not have an effect on the accuracy.
`Fourthly,
`the optical signal may be degraded by both noise and
`motion artifacts. One source of noise is the ambient light received by the
`photodetector. Many solutions have been devised with the aim of minimizing or
`eliminating the effect of the movement of the patient on the signal, and the
`ability of a pulse oximeter to function correctly in the presence of patient
`motion depends on the design of the pulse oximeter. One wayof canceling out
`the motion artefact is to use an extra wavelength for this purpose.
`A further factor affecting the accuracy of a pulse oximeter is the
`method used to calibrate the pulse oximeter. Usually the calibration is based
`on extensive empirical studies in which an average calibration curve is
`determined based on a high numberof persons. By meansofthis calibration
`curve, which relates the oxygen saturation of blood to pulse oximetersignals,
`the average difference between the theory and practice (i.e.
`in-vivo
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`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
`
`measurements) is taken into account. The calibration curve typically maps the
`measured in-vivo signal to a corresponding SpO2value.
`Pulse oximeters, however, can also utilize the Lambert-Beer model
`for calculating the concentrations of the different Hb species. In this method of
`calibration, the measurement signals mustfirst be transformed into signals
`applicable to the Lambert-Beer model for calculation. This transformation
`constitutes the calibration of the pulse oximeter, since it
`is the step which
`adapts the in-vivo signals to the Lambert-Beer theory, according to which the
`pulse oximeter is designed to operate. Thus, the calibration curves can also be
`in the form of transformations used to adapt the actual in-vivo measurements
`to the Lambert-Beer model.
`Transformations are discussed for example in U.S. Patent 6,104,938,
`which discloses a calibration method based on the absorption properties of
`each hemoglobin component,i.e. on the extinction coefficients of blood.In this
`method,
`the effective extinction coefficients are determined for each light
`signal via a mathematical
`transformation from the extinction coefficients
`according to the Lambert-Beer theory.
`However, each patient
`(i.e. subject of the measurement) has a
`calibration curve of his or her own, which deviates from the average calibration
`curve calculated on the basis of a high numberof patients. This is due to the
`fact that for each patient the characteristics of the tissue through whichlightis
`transmitted deviate from those of an average patient. One drawback of the
`current pulse oximeters is that they are incapable of taking this human
`variability into account. Human variability here refers to any and all factors
`causing patient-specific variation in the calibration curve,
`including time-
`dependent changesin the calibration curve of a single patient. As discussedin
`the above-mentioned U.S. Patent, subject-dependent variation can also be
`seen as an effect of a third substance, such as a third hemoglobin species in
`the blood. However,
`the variation can also be interpreted as a subject-
`dependent changein the calibration curve of the pulse oximeter.
`Without compensation for human variability, the accuracy of current
`pulse oximeters is about +2%SpO2. However,in multi-wavelength applications
`in general, and especially if weak absorbers, such as COHb, are to be
`measured, the human variability represents a much more serious problem.
`Therefore, techniques of compensation for these inaccuracies are called for.
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
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`

`

`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
`
`it is an objective of the invention to bring about a solution by means of
`which the effects caused by the tissue of the subject can be taken into account
`when a pulse oximeter is calibrated. In other words,
`it is an objective of the
`present invention to create a pulse oximeter which can take inte account the
`differences caused by an individual subject as compared to the average
`calibration or transformation curve which the current pulse oximeterrelies on.
`A further objective of the invention is to bring about a general-purpose
`solution for the compensation of inaccuracies caused by human variability in
`pulse oximetry, a solution which is not
`limited fo the particular general
`calibration method employed in the pulse oximeter, but which can be applied
`to any pulse oximeter regardless of its current built-in calibration methad.
`
`Summary of the Invention
`These and other objectives of the invention are accomplished in
`accordance with the principles of the present
`invention by providing a
`mechanism by means of which the subject-specific deviation in the tissue-
`induced effects on the accuracy of the pulse oximeter can be taken into
`account.
`
`in the method of the invention, the effect of tissue is taken into
`account and the inaccuracies caused by subject-specific variation in that effect
`are compensated for. This is implemented by defining a nominal calibration for
`the apparatus and making off-line measurements, also termed “initial
`characterization measurements”,
`in order to define the characteristics which
`describe the conditions under which the nominal calibration has been defined.
`Reference data indicating the characteristics are stored for subsequent on-line
`measurements in which light
`transmission through the actual
`tissue is
`measured.
`(Off-line here refers to measurements performed before the
`apparatus is taken into use, whereas on-line refers to the actual
`in-vivo
`measurements.) Subject-specific calibration is then defined based on the
`nominal calibration, the on-line measurements, and the reference data created
`in connection with the off-line measurements. Thus, the inaccuracies are
`eliminated by meansof on-line measurements, which indicate the effect of the
`tissue. Off-line measurements are used to create the reference data so that
`light transmission measured subsequently through the tissue of a subject can
`be used to correct the nominal calibration for that particular subject.
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
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`

`

`CX-1703
`
`WO 03/063060
`
`PCT/FIO3/00089
`
`Thus in one aspect the invention provides a method for compensating
`for subject-specific variability in an apparatus intended for non-invasively
`determining the amount of at least two light absorbing substances in the blood
`of a subject and being provided with emitter means for emitting radiation at a
`minimum of two different wavelengths and with detector means for receiving
`the radiation emitted, the method comprising the steps of
`- calibrating the apparatus using a nominal calibration,
`said
`-
`carrying
`out
`initial
`characterization measurements,
`measurements to include the measuring of radiation received by the detector,
`- based on the characterization measurements, establishing nominal
`characteristics describing conditions under which the nominal calibration is
`used,
`
`storing reference data indicating the nominal characteristics
`-
`established,
`- performing in-vivo measurements on a living tissue, wherein
`radiation emitted through the tissue and received by the detector meansis
`measured,
`- based on the in-vivo measurements and the reference data stored,
`determining tissue-induced changes in the nominal characteristics, and
`in-vivo
`-
`compensating
`for
`subject-specific
`variation
`in
`the
`measurements by correcting the nominal calibration on the basis of the tissue-
`induced changes.
`in a preferred embodiment of the invention the methodis divided in
`two steps so that the first step compensates for the inaccuracies caused by
`tissue-induced wavelength shift and the second step compensates for the
`inaccuracies caused by internal effects occurring in the tissue. The first step is
`then used to correct the extinction coefficients of the blood analytes to be
`measured, and the second step is used to correct the average transformation
`stored in the pulse oximeter.
`in a further preferred embodiment of the invention the effect of the
`temperature is also compensated for in connection with the first step.
`The method is not limited to pulse oximeters explicitly using the
`transformations, but can be applied tc any pulse oximeter. However,
`the
`method is preferably applied to a pulse oximeter based on a transformation,
`since in a preferred embodiment the method is implemented by carrying out
`changes separately in the transformation and in the extinction coefficients.
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`APL_MAS_ITC_00304260
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`MASIMO2067
`Apple v. Masimo
`IPR2022-01299
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
`
`WO 03/063060
`
`PCT/FIO3/00089
`
`the invention provides an apparatus for non-
`In another aspect,
`invasively determining the amountof at least two light absorbing substances in
`the blood of a subject, the apparatus comprising
`- emitter means for emitting radiation at a minimum of two different
`wavelengths,
`receiving said radiation at each of said
`- detector means for
`wavelengths and producing at least two electrical output signals,
`- first signal processing means for processing said output signals and
`producing a modulation signal for each wavelength, whereby each modulation
`signal represents the pulsating absorption caused by the arterialized blood of
`the subject,
`- second signal processing means for applying a predetermined
`calibration on said modulation signals, whereby transformed modulation
`signals applicable in the Lambert-Beer model are obtained,
`- memory means for storing reference data indicating nominal
`characteristics under which said predetermined calibration has been applied,
`- first compensation means, operatively connected to the memory
`means, for determining tissue-induced changes in the nominal characteristics,
`- second compensation means, operatively connected to the first
`compensation means, for defining a subject-specific calibration by correcting
`the predetermined calibration on the basis of the tissue-induced changes, and
`- calculation means, responsive to the second compensation means,
`for determining said amounts.
`In a still further aspect, the invention provides a sensor for collecting
`measurement data for a pulse oximeter
`intended for non-invasively
`determining the amountof at least two light absorbing substancesin the blood
`of a subject, the sensor comprising
`- emitter means for emitting radiation at a minimum of two different
`wavelengths,
`receiving said radiation at each of said
`- detector means for
`wavelengths and for producing at least two electrical output signals,
`-
`storage means
`including reference data
`indicating nominal
`characteristics describing calibration conditions of the pulse oximeter, said
`data allowing apparatus connected to the sensor to determinetissue-induced
`changesin the nominal characteristics when radiation is emitted through said
`tissue.
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`APL_MAS_ITC_00304261
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`Apple v. Masimo
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
`
`Preferred embodiments of the invention are discussed in more detail
`
`below.
`
`Brief Description of the Drawings
`In the following,
`the invention and its preferred embodiments are
`described more closely by referring to the examples shown in FIG. 1 to 12 in
`the appended drawings, wherein:
`FIG. 4 illustrates the basic embodimentof a pulse oximeter according
`to the present invention,
`FIG.2illustrates the signals utilized in the pulse oximeter of FIG. 1,
`10
`FIG. 3 shows the extinction coefficients of two different species of
`hemoglobin as a function of wavelength,
`FIG. 4a to 4f illustrate the average transformation curves for two
`different pulse oximeters,
`FIG. 5 is a flow diagram illustrating the prior art calibration methad,
`FIG. 6 is a flow diagram illustrating the general principle according to
`the presentinvention,
`FIG. 7 is a flow diagramillustrating compensation for the inaccuracies
`caused bytissue-induced wavelength shift,
`FIG. 8 illustrates an example of the transmission curve of human
`tissue, the curve being employed in the compensation of the inaccuracies
`caused by tissue-induced wavelength shift,
`FIG. 9 illustrates the emitter characteristics determined for the
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`compensation,
`FIG. 10 is a flow diagram illustrating the compensation of the
`inaccuracies caused byinternal effects occurringin the tissue,
`FIG. 11 illustrates the low frequency baseline fluctuation utilized in a
`preferred embodimentof the invention, and
`FIG. 12 illustrates an embodiment of a sensor according to the
`invention.
`
`Detailed Description of the Invention
`Below,
`the solution according to the invention is discussed with
`reference to a pulse oximeter utilizing the above-mentioned transformations
`and four different wavelengths. As mentioned above, U.S. Patent 6,104,938
`discloses a pulse oximeterutilizing the transformations.
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
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`

`

`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
`
`FIG. 1 is a block diagram of a pulse oximeterutilizing four different
`wavelengths. Light from four different LEDs 10a, 10b, 10c, and 10d, each
`operating at a respective wavelength, passes into patient tissue, such as a
`finger 11. The light propagated through orreflected from the tissue is received
`by a photodetector 12, which converts the optical signal received into an
`electrical signal and feeds it to an input amplifier 13. The amplified signal is
`then supplied to a control unit 14, which carries out caiculation of the amount
`of the Hb-derivatives in the blood. The contro! unit further controls the LED
`
`drive 15 to alternately activate the LEDs. As mentioned above, each LED is
`typically illuminated several hundred times per second.
`When each LEDis illuminated at such a high rate as compared to the
`pulse rate of the patient, the control unit obtains a high number of samples at
`each wavelength for each cardiac cycle of the patient. The value of these
`samples (i.e. the amplitude of the received signal) varies according to the
`cardiac cycle of the patient, the variation being caused by the arterial blood, as
`mentioned above. The control unit 14 therefore utilizes four measurement
`signals, as shownin FIG. 2, each being received at one of the wavelengths.
`In orderfor variations in extrinsic factors, such as the brightness of the
`LEDs,sensitivity of the detector, or thickness of the finger, to have no effect on
`‘the measurement, each signal received is normalized by extracting the AC
`component oscillating at the cardiac rhythm of the patient, and then dividing
`the AC component by the DC componentofthe light transmission orreflection.
`The signal thus obtained is independent of the above-mentioned extrinsic
`factors. Thus in this case the control unit utilizes four normalized signals, which
`AC,
`are in the following denoted with 44, “FE! where i
`is the wavelength in
`
`question (in this basic embodiment of the multi-wavelength pulse oximeter
`i=1,2,3, 4), AC;
`is the AC component at wavelength i, and DC; is the DC
`component at wavelength i. The signals dA; are also referred to below as
`modulation signals. The modulation signals thus indicate how absorption is
`affected by the arterial blood of the patient.
`The above-described measurement arrangement corresponds to a
`conventional four-wavelength pulse oximeter. The method of the present
`invention is implemented in the contro! unit of the pulse oximeter on the basis
`of the four modulation signals described above,i.e. the novelty of the system
`resides within the control unit itself. However, to be able to perform the self-
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`IPR2022-01299
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`

`

`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
`
`calibration in conjunction with each patient, the control unit requires some pre-
`calculated data, which is stored in the memory (M1) of the pulse oximeter.
`Instead of being stored in conjunction with the control unit, this data, or at least
`part of it, can also be stored in the sensor part of the pulse oximeter. The
`sensorpart, including at least the LEDs and the photo detector, is connected
`to the signal processing part, which includes the control unit. Consequently,
`depending on the overall configuration, the novelty can also reside partly in the
`sensor. The operation of the pulse oximeter is discussed in more detail below.
`The theory of pulse oximetry is generally presented as being based
`on the Lambert-Beer Law. Accordingto this theory, light transmission through
`the tissue at each wavelength is exponentially dependent on the absorbance
`of the tissue (Eq. 1). This theory is generally accepted and established as a
`good modelfor pulse oximetry.
`Next
`to be discussed is the theory and formalism on which the
`method of the invention is based.
`According to the Lambert-Beer theory and for a system of two
`analytes, the signals described above can be presented asfollows:
`dA, =dAx(ef?x HbO, +2" x RHD)
`dA, =dAx (efx HbO, + 63" x RHb)
`dA, =dAx (ef?x HBO, +e” x RHb)
`dA, =dAx(ei™ x HbO, +e)” x RHB)
`RHb=1- HbO,
`
`where dA is a common factor which depends on the absolute values,
`inter alia on the total amount of hemoglobin, ¢;"”is the extinction
`i.e.
`coefficient of oxyhemoglobin at wavelength i (=1-4), 4;""is the extinction
`coefficient of deoxyhemoglobin at wavelength i, HbOz is the concentration
`fraction of oxyhemoglobin, and RHb is
`the concentration fraction of
`deoxyhemoglobin.
`Using a matrix notation, the above dependencies can be expressed
`for a system of n wavelengths and n analytes as follows:
`(dA,
`Ey sors Ein
`FBX,
`| dA, cx] Sas Sn | HbX,
`(a,
`En sof. Onn
`AbX,
`where dA; is the differential change in absorption (i.e. the modulation
`signal) at wavelength i, sy is the extinction coefficient of the hemoglobin
`
`2),
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`PAGE 10 OF 48
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`APL_MAS_ITC_00304264
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`MASIMO2067
`Apple v. Masimo
`IPR2022-01299
`
`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
`
`WO 03/063060
`
`PCT/FIO3/00089
`
`10
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`derivative HbX; at wavelength ii, and the constant C accounts for the change
`of units to fractional percentages of the concentrations of the analytes Hbx).
`FIG. 3 shows
`the extinction coefficients
`(¢”" and «”’) of
`
`oxyhemoglobin (HbOz) and deoxyhemoglobin (RHb) as a function of the
`wavelength. Point P shown in the figure is the isobestic point of oxyhemoglobin
`(HbOz) and deoxyhemoglobin (RHb). The point has the special property that
`the modulation signal at the wavelength in question does not depend on the
`respective proportions (relative concentrations) of the hemoglobin species.
`Thus at the wavelength of point P the effect of the relative concentrations of
`oxyhemoglobin and deoxyhemoglobin on the result of the measurementis nil.
`It should be noted, however, that the modulation signal is independent of the
`relative concentrations only, not of the absolute concentrations. Thus,
`the
`absolute amount of the hemoglobin species has an effect on the result of the
`measurement.
`
`Asis known, there is a difference between the Lambert-Beer theory
`and the practical measurements. The difference is due to the fact that the
`Lambert-Beer theory does not take into account the scattering and non-
`homogeneity of the tissue, whereas the actual extinction coefficients are also
`dependent on the scattering of light caused by the tissue and blood, and on
`the combined effect of absorption and scattering. The larger the proportion of
`the attenuation caused by absorption and scattering,
`the larger is
`the
`correction needed between the actual and the theoretical
`(non-scatier)
`domains. This correction between these two domains can be represented by
`the transformation curves discussed above, by means of which the actual in-
`vivo measurements are mapped to the Lambert-Beer model.
`The transformation can be expressed, for example, as follows:
`NE? = gi! (we)
`(3),
`
`dA
`
`where NV, = is the modulation ratio (the superscript indicating the
`domain) in the form of a polynomial function (the subscripts k and / indicating
`the wavelengths in question), and g is the transformation (the subscript “1”
`denating the inverse function).
`illustrate the average transformation curves
`Figures 4a to 4f
`measured for a pulse oximeter, where the two wavelengths for measuring the
`two species of hemoglobin are 660 nm and 900 nm andthe third wavelength is
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
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`WO 03/063060
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`PCT/FIO3/00089
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`11
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`either 725 nm or 805 nm. Figures 4a to 4cillustrate the transformation curves
`for a pulse oximeterwith the third wavelength being 725 nm, and Figures 4d to
`4f illustrate the transformation curves for a pulse oximeter with the third
`wavelength being 805 nm. Each curve shows the Lambert-Beer Ny; as a
`function of the in-vivo Ny at wavelengths k and /.
`FIG. 5 is a flow diagram describing the general measurement
`principle described in U.S. Patent 6,104,938.
`in this method,
`the above-
`mentioned N,"’ values are first determined from the dA; values measured
`
`(step 51). The average transformations gw are then used to convert the
`measured in-vivo values to values NV,” , which can be used in the ideal
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`Lambert-Beer model (step 52). Other input values needed for the Lambert-
`Beer model are also determined (step 53). In practice these input values are
`the ideal (nominal) extinction coefficients of the analytes to be measured, the
`extinction coefficients being given for the center wavelengths used in the
`measurement. The converted transformation values and the nominal
`input
`values (Le. nominal extinction coefficients) are then used according to the
`Lambert-Beer modelto calculate the concentrations of the desired analytes
`(step 54). Thus in this approach the in-vivo values N,7"”’ measured from the
`
`tissue are converted to the ideal in-vitro (cuvette) environment, where the ideal
`oximetry model(i.e. the Lambert-Beer model) is applied to yield the desired
`concentrations.
`In the standard two wavelengthpulse oximetry the prior art technique
`is to map the modulation ratio Ni," directly to the SpO2 percentage
`
`measured. In this simple case the transformation is not necessary, though the
`transformation technique together with the solution in the Lambert-Beer
`domain can beutilized as well.
`
`There are two basic ways to determine the average transformation, a
`theoretical approach and an empirical approach. In the empirical approach the
`measurements are madein the tissue by taking blood samples and measuring
`the actual proportions of the hemoglobin species and then determining the
`value of V7” onthe basis of the measured proportions. The transformationis
`then obtained as the relationship between the values based on the blood
`samples and the values given by empirical measurements as measured by the
`pulse oximeter. The theoretical approach, in turn, is based on a knowntissue
`model, which takes into account the characteristics of the tissue as referred to
`above, which are ignored in the Lambert-Beer model. A first value is
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`PAGE 12 OF 48
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`APL_MAS_ITC_00304266
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`MASIMO 2067
`Apple v. Masimo
`IPR2022-01299
`
`

`

`CX-1703
`
`WO 03/063060
`
`PCT/FIO3/00089
`
`12
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`determined for in-vivo Ny by means of the tissue model and a second value on
`the basis of the Lambert-Beer model. The tissue parameters of the model are
`determined so that the known 2-wavelength calibration (so-called R-curve)is
`reproduced. Then using these tissue parameters and the wavelength
`dependence of the tissue model,
`the relation of the in-vivo Nu and the
`Lambert-Beer Ny is extrapolated to other wavelengths in order to obtain the
`transformations at these new wavelengths. Thus in the theoretical approach
`no new empirical measurements are made.
`in practice the transformation can be a quadratic equation yielding a
`correction of the order of 20 percent to the measured Nu” value, for
`example. As discussed below, the transformation data (i.e. the transformation
`curves) are preferably stored in numeric form in the pulse oximeter or the
`sensor. The number of transformation curves stored in the pulse oximeter can
`vary, depending on the number of wavelengths used, for example. Typically
`there is a transformation curve for each wavelength pair.
`As mentioned above, the accuracy of a pulse oximeter utilizing an
`average transformation is not necessarily sufficient, especially if analytes
`which are weak absorbers are to be measured or if two analytes absorb
`similarly, wherebyit is difficult to distinguish the said analytes from each other.
`In the present
`invention the accuracy of the pulse oximeter is
`improved by taking into account the subject-specific light transmission through
`the tissue, and changing the values