111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111
`US 20040059236Al
`
`(19) United States
`( 12) Patent Application Publication
`MarguUes et al.
`
`(JO) t•ub. No.: US 2004/0059236 Al
`Mar. 25, 2004
`(43) Pub. Date:
`
`(54) METHOD AND A PPARAT US FOR
`MONITORING THE AUTONOMIC NERVOUS
`SYSTEM
`
`(76)
`
`Inventors: Lyle Aaron Margulies, Seatl le, WA
`(US); David 8. Harrell, Mukilteo, WA
`(US); Miclmcl A llen Riggins, Scaule,
`WA (US)
`
`C'orrcspoodcoce Address:
`GARRISON ASSOCIATES
`200 1 SlXTH AVENUE
`sun'E 3300
`SEA1.fLE, WA 981212522
`
`(21) Appl. No.:
`
`10/666, 12 1
`
`(22) Filed:
`
`Scp. 19, 2003
`
`Related U.S. Application Data
`
`(60) Provisional application No. 60/412,310, fi led on Sep.
`20,2002.
`
`Publication Classificat ion
`
`Int. C l.7
`.......................... ............................. A618 5/02
`(51)
`(52) U.S. C l. .. ............................................................ 600/500
`
`(57)
`
`ABSTRACT
`
`An apparatus and method for detection and monitoring of
`au tonomic nervous system (ANS) activity in humans, pri(cid:173)
`marily in the field of s leep research. The present invention
`discloses a portable, simple, and cost-effective electronic
`device containing hardware and software that permits real(cid:173)
`time monitoring of a pulsatile blood volume waveform
`obtained through use of a pbotoplethysmograpbic (optical
`volume detecting) probe, thereby allowing signal condition(cid:173)
`ing, waveform slope analysis, display, recording, and output
`of pulse transitional slope data represen tative of activity in
`the ANS.
`
`LIGHT SOURCE
`
`FINGER VASCULAR BED
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`---~
`
`PHOTODETECTOR
`
`001
`
`Apple Inc.
`APL1013
`U.S. Patent No. 9,289,135
`
`

`

`Patent Application Publication Mar. 25, 2004 Sheet 1 of 7
`
`US 2004/0059236 Al
`
`FIG.l
`
`LIGHT SOURCE
`
`0 0 0 0 0 0
`
`FINGER VASCULAR BED
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`---~
`
`PHOTOOETECTOR
`
`ABSORPTION
`
`ABSORPTION
`DUE TO TISSUE
`
`TIME
`
`FIG.2
`
`002
`
`

`

`Patent Application Publication Mar. 25, 2004 Sheet 2 of 7
`
`US 2004/0059236 Al
`
`FIG.3
`
`~-------- PEAK TOP
`
`SLOPE
`
`PERIPHERAL PULSE WAVEFORM
`
`dP/dt
`
`003
`
`

`

`~
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`
`FIG.4C
`
`NTG
`
`AGT
`
`CONTROL
`
`FIG.4B
`
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`
`AGT
`
`CONTROL
`
`FIG.4A
`
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`
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`
`CONTROL
`
`A oF
`
`AoP
`
`SDPTG
`
`PTG
`
`ECG
`
`004
`
`

`

`Patent Application Publication Mar. 25, 2004 Sheet 4 of 7
`
`US 2004/0059236 At
`
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`
`229 457 685 913 1141 1369 1597 1825 2053 2281 2509 2737 2965 3193 3421 3649 3877
`
`HEART BEATS
`
`FIG.7B
`
`$4
`
`S3
`
`S2
`STAGE
`SLEEP
`S1
`SCORED REM
`
`AWK
`
`
`
`MT
`
`II I II I
`
`...
`
`I I
`
`I
`
`I I I t Az I II
`
`II
`
`A A
`
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`
`60 II A A ..
`
`70~--------~--------------------------r-------------~~
`
`eo~------------------------------------------------------~
`
`FIG.7A
`
`l I
`
`I w II II
`
`HEART BEATS
`
`40+---------------~-------(
`
`IV ¥' I:A,.IFI.lllA mA.xA .f II q11 llf 11'1 IA,.~'ll' 1111 IIIIVIP'
`
`\
`
`50 I llllllllllf IJIIV
`
`PERCENTAGES
`
`RATIO
`SLEEP
`
`006
`
`

`

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`
`INTERFACE
`COMPUTER
`
`816
`
`STORAGE
`
`MULTIMEDIA
`
`CARD
`
`815
`
`FIG.8
`
`SERIAL
`
`110
`
`811
`
`SPIBUS
`
`810
`
`TRANSMIT BUTTON
`
`START/STOP BUTTON
`
`CONTROLS
`
`USER
`
`POLYGRAPH
`
`OUTPUT
`
`813
`
`SLOPE RATIO
`
`OUTPUT
`
`814
`
`POLYGRAPH
`
`DISPLAY
`
`BAR GRAPH
`
`89
`
`88
`
`DISPLAY
`
`BAR GRAPH
`
`BICOLOR
`
`LED
`
`9V BATTERY AND
`
`3.3V POWER
`
`SUPPLY
`
`81
`
`FREQUENCY
`
`FILTER
`
`HIGH
`
`FREQUENCY
`
`FILTER
`
`LOW
`
`82
`
`INTERFACE
`
`PROBE
`
`PROBE
`SP02
`
`83
`
`007
`
`

`

`Patent Application Publication Mar. 25, 2004 Sheet 7 of 7
`
`US 2004/0059236 At
`
`FIG.9
`
`DISPOSING A
`PHOTO-PLETHYSMOGRAPHIC PROBE
`PROXIMAL TO A SINGLE BODY PART
`
`DERIVING A CONTINUOUS PULSATILE
`BLOOD VOLUME WAVEFORM AS A
`FUNCTION OF PULSE AMPLITUDE AND
`TIME
`
`DEFINING A TIME INTERVAL FOR
`CALCULATION OF A SLOPE OF THE
`PULSATILE BLOOD VOLUME WAVEFORM
`
`PERFORMING CONTINUOUS
`CALCULATION OF THE SLOPE OF THE
`RISING SEGMENT OF EACH BLOOD
`VOLUME WAVEFORM OVER DEFINED
`TIME INTERVAL
`
`PROCESSING INPUT DATA TO DIVIDE
`PEAK AMPLITUDE VALUES BY A GIVEN
`TIME CONSTANT
`
`ELIMINATING FROM FURTHER
`CALCULATION SLOPE VALUES OF LESS
`THAN ONE
`
`~
`
`SIGNAL PROCESSING, CONDITIONING,
`AND ARTIFACT REJECTION
`
`AMPLIFYING AND FILTERING SLOPE
`VALUES
`
`t
`
`PROVIDING AN
`OUTPUT DISPLAY
`OF INFORMATION
`REPRESENTATIVE
`OF SLOPE VALUES
`
`PROVIDING DATA
`OUTPUT
`REPRESENTATIVE
`OF SLOPE VALUES
`FOR USE BY
`OTHER DEVICES
`
`.t
`
`STORING
`ELECTRONIC DATA
`REPRESENTATIVE
`OF SLOPE VALUES
`
`008
`
`

`

`US 2004/0059236 Al
`
`Mar. 25, 2004
`
`1
`
`METHOD AND APPARAT US FOR MONITORING
`T HE AUTONOMIC NERVOUS SYSTEM
`
`CROSS-REFERENCE TO RELATED
`APPUCAfJON
`[0001) This applica tion claims benefit of United States
`Provisional Application Serial No. 60/412,310 entitled
`Method and Apparatus for Monitoring the Autonomous
`Nervous System, filed Sep. 20, 2002.
`
`TECHNlCAL FIELD
`[0002] This invention rela tes to medical devices, and more
`particularly
`to physiological monitoring methods and
`devices used for detection of autonomic nervous system
`(ANS) activity in the field of sleep research. The present
`invention discloses a portable, simple, and cost-etiective
`electronic sleep diagnostic device containing hardware and
`software that permits record ing and signal conditioning of a
`pulsatile blood volume waveform obtained tluougb use of a
`photoplethysmographic (optical volume detecting) probe,
`thereby allowing analysis pulse transitional slope da ta that is
`representative of activity in the autonomic nervous system
`(ANS).
`
`BACKGROUND OF THE INVENTION
`[0003) Cardiovascular risk is direct ly linked to sleep
`related breathing disorders (SRBD). The number of U.S.
`laboratories that study sleep, roughly 2,792, is incredibly
`low when compared to the number of Americans estimated
`to have a chronic SRBD, just over 4{) million. The average
`number of beds per lab is 3.6 bringing the total number of
`beds in wbich to do a sleep study to roughly 10,000. This
`means that to test all 40 million Americans, there would be
`4,000 patients that would be seen per bed. If sleep tests were
`run 365 days per year, the result is an astounding 11 years
`of conclusive tests needed to be run to test the current
`popu lation of individuals suffering form SRBD. The le ng1 h
`of time increases as one considers the actual number of days
`per year sleep labs actually test patients, plus the amount of
`tests that need to be re-run due to inconclusive testing, plus
`the number of patients that continually need to be retested to
`see if their treatment is functioning properly. Given this
`scenario, it is no shock tha t wait times for patients to be
`scheduled for a sleep test can typically range from six weeks
`to six months. The problem will only increase, as "it is
`estimated that nearly 80 million Americans will have a sleep
`problem by the year 2010 and 100 million wi ll have one by
`the year 2050." Clearly then, the problem with wait time for
`testing should be addressed immediately to relieve pent up
`demand.
`[0004) The current "gold standard" for testing sleep
`related breathing disorde rs is full polysom nography. Full
`polysomnograp hy
`is, however, qui te
`labor
`intensive,
`requires considerable instrumentation and is therefore rat her
`expensive to conduct. As a result, many sleep laboratories
`bave found i.t difficult to keep up witb tbe demand for tllis
`test, and a long waiting list becomes the norm. Given tha t
`obstructive sleep apnea (OSA) is quite prevalent, leads to
`serious complication.<; and that treatmen t options exist, it is
`important that individuals su.ffering from the disease arc
`identified.
`
`[0005) The need to study the ANS has been realized in
`academia for a considerable time. It is known in the field of
`
`microneurography that rapid-eye movement (REM) sleep is
`as.-;ociated with profound sympathetic activity. It has also
`been found that arousals from non-rapid-eye movemen t
`(NREM) el.icits K complexes that are associated with sym(cid:173)
`pathetic activity. The sympathetic di vision of the ANS
`prepares a body for movement. Arousals require movemen t
`and hence an arousal requires sympathetic activation.
`
`[0006) Generally, patients with OSA, a type of SRBD,
`have extremely disrupted sleep and terribly high daytime
`somnolence. Obstructive sleep apnea events are always
`accompanied by an acute rise io systolic blood pressure
`(rises in systolic blood pressure are associated with sympa(cid:173)
`thetic activation), even when the usual EEG criteria for
`arousals are not met (a recognizable cor tica l electroencepha(cid:173)
`lographic arousal). The duration of the apnea of individuals
`that demonstrate EEG arousal and those that do not meet the
`usual criteria for defining an arousal have been found to be
`identical. The pleural pressure peak, at the end of apnea, is
`identical between the two types of arousals, as are the EEG
`frequencies. These findings suggest that monitoring tbe
`cardiac changes of sleep is a more accurate measurement.
`
`[0007)
`It has been demonstrated tha t apneic episodes
`result in progressive increases in sympathetic nerve activity.
`The increases are roost marked toward the end of the apnea,
`wben a patient moves. These findings are exactly what is
`excepted of sympathetic activation an d its relationship to
`arousals in patients with SRBD.
`
`[0008] Because cardiovascular control during sleep is pri(cid:173)
`marily dictated by brain states that produce profound varia(cid:173)
`tion in ANS activity, many studies have been conducted to
`monitor tbe ANS. Since the data shows clearly that moni(cid:173)
`toring the ANS or cardiac changes in sleep yields more
`accurate data defining an arousal in sleep, it is clear that
`diagnostic studies must include ANS or cardiac monitoring.
`[0009)
`It has been shown that in transitions from NREM
`to REM s leep, heart rate accelerations !>recede the EEG
`arousals marki ng the onset of REM. Therefore, not only
`does monitoring ANS activity give tbe clinician a possibly
`more accurate study, but also changes in ANS activity
`precede that information being observed via the EEG elec(cid:173)
`trodes.
`
`[0010) 1bere are two existing technologies tbat attempt to
`monitor the ANS, namely pulse transit time (PTT) and
`peripheral arterial tonomet ry (PAT). Neither PTr nor PAT
`can Jay claim to monitoring tbe ANS witbout adding addi(cid:173)
`tional sensors. PTT requires the use of ECG electrodes tha t
`may be difficult for a patient to self-apply due to skin
`cleaning and shaving requirements. PAT requires a very
`costly gauntlet-type device with a single-usc finger pressure
`cuff. Also, the addition of extra sensors adds to noise artifact
`and difficulty in patient use. 1t is therefore an object of the
`present invention to provide an improvement over existi ng
`PTT and PAT technology through a more economical and
`more easily used device wi thout need of additional sensors.
`
`[0011) Several disclosures have been made in the prior art
`that teach methods and devices for diagnosis and monitoring
`of sleep breathing disorders using physiological data
`obtained from pulse oximetry-derived waveforms.
`
`[0012) U.S. Pat. No. 5,398,682 to Lynn (Mar. 21, 1995)
`discloses a method and apparatus for the diagnosis of sleep
`apoea utilizing a single interface witb a human body part.
`
`009
`
`

`

`US 2004/0059236 Al
`
`Mar. 25, 2004
`
`2
`
`More specifically, a device is disclosed for diagnosing sleep
`apnea by identifying the desaturation and resatura tion events
`in oxygen satwation of a patient's blood. The slope of ibe
`events is determined and compared against various infor(cid:173)
`mation to determine sleep apnea.
`
`[0013) U.S. Pat. No. 6,363,270 Bl to Colla, eta!. (Mar. 26,
`2002) discloses a met hod and apparatus for monitoring the
`occurrence of apneic and bypopneic arousals utilizing sen(cid:173)
`sors placed on a patient to obtain signals representative of at
`least two physiological variables, including blood oxygen
`concentration, and providing a means for recording the
`occurrence of arousals. Obtained signals pass through con(cid:173)
`ditioning circuitry and then processing circuitry, where
`correlation analysis is performed. A coincident change in at
`least two of the processed signals are indicative of ibe
`occurrence of an arousal that in turn indicates an apneic or
`bypopneic episode bas occurred. A patient thus can be
`diagnosed as suffering conditions such as obstructive sleep
`apnea.
`
`[0014] U.S. Pat. No. 6,529,752 B2 to Krausman and Allen
`(Mar. 4, 2003) discloses a method and apparatus for count(cid:173)
`ing ibe number of sleep disordered breaibing events expe(cid:173)
`rienced by a subject within a specified time period. Such a
`counter comprises: (1) an oxygen saturation level sensor for
`location at a prescribed site on the subject, (2) an oximetry
`conditioning and control module that controls the operation
`of the sensor and converts its output data to oxygen satu(cid:173)
`ration level data, (3) a miniature monitoring unit having a
`microprocessor, a memory device, a timer for use in time(cid:173)
`stamping data, a display means and a recall switch, and (4)
`firmware for the unit that directs: (i) tbe sampling and
`temporary storage of the oxygen saturation level data, (ii)
`the unit to analyze using a specified method the temporarily
`stored data to identify and count the occurrence of ibe
`subject's disordered breathing events, and to store the time
`of occurrence of each of these events, and (iii) the display
`means to disp lay specified information pertaining to the
`counts in response to the actua6on of the recall switch.
`
`[0015] U.S. Pat. No. 6,580,944 Bl to Katz, et al. (Jun. 17,
`2003) discloses a method and apparatus for identifying the
`timing of the onset of and duration of ao event characteristic
`of sleep breathing disorder while a patient is awake. Chaotic
`processing techniques analyze data concerning a cardiores(cid:173)
`piratory function, such as oxygen saturation and nasal air
`Oow. Excursions of the resulting signal beyond a threshold
`provide markers for delivering the average repetition rate for
`such events that is useful in the diagnosis of obstructed sleep
`apnea and other respiratory dysfunctions.
`
`[0016] The above references all make usc of oxygen
`saturation data obtained through pulse oximetry to deter(cid:173)
`mine arousals and/or sleep breathing disorders. Each nec(cid:173)
`essarily requires additional analysis and calculation of blood
`oxygen concentrations in order to render information useful
`specifically in the diagnosis and monitoring of sleep breath(cid:173)
`ing disorders. It is therefore another object of the present
`invention to J>rovicle a more simplified method of obtaining
`and analyzing physiological data that accurately represents
`ANS activity.
`
`BRIEF SUMMARY OF Ti lE INVENTION
`
`[0017)
`It is an object of the present invention to overcome
`one or more of the problems with the prior art. In one
`
`preferred embodiment the present invention provides a
`method and apparatus for improved monitoring of ANS
`activity using a single patient sensor.
`
`[0018] A variety of breathing disturbances may occur
`during sleep, including snoring, bypoventilation, apnea,
`increased upper-airway resistance, and asthma related con(cid:173)
`ditions. This project proposes development of a novel device
`that can noninvasively and accurately detect frequent brief
`micro arousals that are not well identified by conventional
`airflow, respiratory effort, pulse oximetry and EEG methods.
`These subcortical events result from increased respiratory
`effort and cause disruption of nocturnal sleep, leading to
`excessive daytime somnolence.
`
`[0019) Since microarousals have been associated with
`changes in autonomic system outflow, this invention pro(cid:173)
`vides for a small, portable device that analyzes ihe shape of
`the arterial finger pulse, thereby detecting on a beat by beat
`basis changes in vascular tone directly attributable to
`microarousals. The present invention uses a photopletbys(cid:173)
`mographically derived arterial blood volume waveform for
`monitoring changes in peripheral arterial vascular tone, in
`conjunction with AID converters and a microcontroller for
`analyzing the morp hology of the pulsatile signal.
`
`[0020) The method of the present invention provides for
`detection of microarousals tbat com1)ares favorab ly with
`detection by pulse transit time (PTT) devices, EEG analysis,
`ECG analysis, esophagal pressure (Pes) or some combina(cid:173)
`tion of these methods. Although PlT aod peripheral arterial
`tonometry (P~I) have boib been receiving much attention as
`techniques for detecting changes in the ANS during sleep
`studies, PAT is relatively expensive and JYIT bas implemen(cid:173)
`tation problems caused by motion artifact.
`
`[0021]
`It is a further object of the present invention to
`provide an apparatus that utilizes transmitted Light intensity
`from an existing FDA approved pulse oximeter probe so that
`no additional device is attached to tlbe patient. Valuable
`diagnostic infom1ation can then be extracted through e lec(cid:173)
`tronic processing of this existing data.
`
`[0022) Normalization is a method to correct for the pho(cid:173)
`toplethysmograpbic pulse signal morphological changes
`based on finger position (as opposed to actual changes of
`autonomic activity.) PTI' and PAr lack a means for signal
`normalization and therefor cannot correct for finger position
`changes. Norma.lization provides immunity
`to artifact
`caused by both e levation changes of the finger probe, and
`changes in blood flow due to arterial compression during
`patient positional changes. It is therefor another object of the
`present invention to provide a means of normalization in
`order to ensure appropriate artifact suppression.
`
`[0023) Since pulse oximeters use an alternating flashing of
`two diiierent wavelength LEOs, the present invention is
`intended to synchronize with tbe desired LED in order to
`examine the transmitted intensity due to a single wave(cid:173)
`length. Alternatively, certain models of oximeter OEM mod(cid:173)
`ules provide an analog or digital output that can be utilized
`directly by the present invention.
`
`[0024] Another objective is to provide algorithms for
`slope detection, peak to peak height, ao.d normalization may
`be performed either with firmware \vithin ibe present inven(cid:173)
`tion apparatus, or by software after the data is downloaded
`ioto a polysomnograpb or otber data processing device.
`
`010
`
`

`

`US 2004/0059236 Al
`
`Mar. 25, 2004
`
`3
`
`It is a further objective of the present invention to
`[0025)
`provide a means of data storage and transfer, and to provide
`a method of displaying the observed changes in slope.
`Alternative embodiments display these changes as a wave(cid:173)
`form, light bars, and/or numerical information.
`
`BRI EF DESCRIPDON OF THE DRAWINGS
`
`[0026] FIG. 1 shows a schematic representation of a
`typical pulse oximeter sensing configuration on a finger.
`[0027) FIG. 2 shows a graphic representation of the
`components of vascular tis.'5ue that contribute to light
`absorption plotted as absorption versus time.
`[0028] FIG. 3 shows a graphic representation of a single
`peripheral pulse waveform plotted as volume versus time.
`
`[0029] FLG. 4 shows comparative physiological wave(cid:173)
`forms fo llowing administration of vasoactive agents.
`[0030] FIG. 5 shows a second derivative waveform con(cid:173)
`sisting of a, b, c and d waves in systole, and an e wave in
`diastole.
`[0031] FIG. 6 shows a graphic representation of changes
`in Normalized Slope plotted as slope ratio versus heart beats
`while subject performs Valsalva maneuver.
`[0032] FIG. 7 s hows a sleep stage hypnogram of an hour
`and a quarter sleep study.
`[0033) FIG. 8 shows a block diagram of the present
`invention appa ratus.
`[0034] FIG. 9 shows a block diagram of the present
`inveotion method.
`
`DETAILED DESCRIPTION OF THE
`INVENDON
`
`[0035] A variety of breathing disturbances may occur
`during sleep, including snoring, bypoveniilation, apnea,
`increased upper-airway resistance, and a~tbma related con(cid:173)
`d itions. The present invention discloses a method and appa(cid:173)
`ratus tbat can noninvasively and accurately detect frequent
`brief '"mieroarousals" (small amplitude subcortical distur(cid:173)
`bances that disrupt normal sleep) that are not well identified
`by conventional airflow, respiratory eftort, pulse oximetry
`and EEG methods. These subcortical events result from
`increased respiratory effort and cause disruption of nocturoal
`sleep, leading to excessive daytime somnolence.
`
`[0036] Microarousals can be detected using data obtained
`from the absorbance of visible or infrared light in a finger or
`otber body part of a patient, and by analyzing changes in tbe
`obtained peripheral blood volume waveform that are indica(cid:173)
`tive of microarousals . Specifically, sufficient information is
`contained in slope variations of the rising edge of tbe
`pulsatile blood volume waveform to allow analysis of
`changes in ihe autonomic nervous system (ANS). Tbis
`technology is herein referred to as pulse transi tional slope
`(PTS). Both ANS and bemodynaroic responses occur during
`obstructive sleep apnea and are iofiuenced by apnea, hypop(cid:173)
`nea, hypercapnea, and a.rousal.
`
`[0037] Analysis of the noninvasive blood pressure pulse
`wave has been shown to be usef11l for evaluation of vascula r
`load and aging. Pressure transducers located at a palpable
`artery, such as the carotid, femora l, or radial artery provided
`
`a detailed waveform of pressure versus time. Tbi'> continu(cid:173)
`ous pulse wave tracing contains precise waveshape, fre(cid:173)
`quency, and inflection information easily discernable by tbe
`buman eye that is not available from only systolic and
`diastolic pressure numerics. Tbe progression from pressure
`transducers to pbotopletbysmography allows detection of
`the pulse wave at sites not easily paLpated, including the
`finger and earlobe. Pbotopletbysmography detects
`the
`changes io the amount of light absorbed by hemoglobin,
`which corresponds to changes in blood. volume. Changes in
`amplitude of the photoplethysmographic wave bave been
`used to evaluate arterial compliance, but the wave contour
`itself was not used, as is disclosed by tbe present invention.
`
`[0038] Plethysmography is tbe measurement of volume
`changes of tissue or an organ. Photopletbysmography mea(cid:173)
`sures blood volume changes in a tissue using the fractional
`cbange in light transmission. One of the most common
`applications of this technology is the noninvasive measure(cid:173)
`ment of the oxygen saturation of the hemoglobin in red
`blood cells tbrough a tecboique called pulc;e oximetry. FIG.
`1 shows a typical pulse oximeter sensing configuration on a
`linger. Typically, two different wavelengths of light (e.g. 660
`and 805 nm) are applied to one side of a finger and the
`received intensity is detected on the opposite s ide after
`experiencing some absorption by the intervening vascular
`tis.'5ues. Tbe amount of absorption (and conversely transmis(cid:173)
`sion) is a function of the thickness, color, and structure of the
`skin, tissue, bone, blood, and otber tissues tha t tbe light
`traverses.
`
`[0039) The present invention is specifically directed to
`alpha andrenergic receptor sites, tbe activation of tbese
`receptors at certain locations on the body resulting in
`physiological responses such as peripheral vascula r resis(cid:173)
`tance, mydriasis, and contraction of pilomotor muscles,
`which are represen tative of sympathe tic nervous system
`activity. Tbe preferred locations generally include the fingers
`and the big toe (other sites are under investigation), due to
`a desirable lack of beta or parasympathetic receptors at those
`locations on tbe body.
`
`[0040] The transroilling light comes from ligbt emitting
`diodes (LEOs), typically in the visible red and the invisible
`infrared (rR) spectrums. The optical receiver may be a
`photodiode, photoresistor, or solar cell By using two dif(cid:173)
`ferent wavelengths, each with different absorbance charac(cid:173)
`teristics in oxygenated and deoxygena ted blood, the inten(cid:173)
`sity ratio between tbe two received signals can be analyzed,
`and not just the intensity. Therefore tbe attenua ting tissues
`mentioned earlier do not affect the ratio of tbe intensities,
`which via a look-up table can determine the oxygen satu (cid:173)
`ration percent in the linger vasculature.
`
`[0041] FIG. 2 shows the components of vasculature tis.'5ue
`that cont ribute to ligbt absorption. The static or de compo(cid:173)
`nent of the received optical signal represents !igbt absorption
`by tbe tissue, venous blood, pigments and other structures.
`The present invention is concerned wiLb the ac, or pulsatile
`component because tbe focus is on examining the wave
`sbape of the systolic portion of the blood volume waveform.
`Electronically, the de component is removed with a simple
`resistor-capacitor high pass circuit !bat bas a -3 dB fre(cid:173)
`quency of arouod one Hertz.
`
`011
`
`

`

`US 2004/0059236 Al
`
`Mar. 25, 2004
`
`4
`
`[0042) The amount of light passing through the finger is
`called traosmittance, T, and is defined by:
`
`T=l/lo
`
`[0043) where lo is the intensity of the incident light and I
`is the intensity of the transmiHed light.
`
`[0044) The amount of light of a specified wavelength
`absorbed by a substance is directl y proportional to both the
`leogth of the light path and the coocentra tioo of the material
`within the light path. Tbe absorbance, A, is defi ned as the
`negative logarithm of the transmittance, or:
`
`A=-tog T=-tog 1/lo=aCL
`[0045] where a is a constant called the extinction coeffi(cid:173)
`cient and is dependent on the wavelength of the light passing
`th rough the substance and on the chemical nature of the
`substance. C is the concentration of the substance and Lis
`the path length of the absorbing ma terial.
`
`[0046) The present invention makes use of just one of the
`wavelengths from the pulse oximeter probe, since tbe objec(cid:173)
`tive is to observe only rela tive changes in the pulse wave
`shape, which in turn is derived from systolic blood volume
`changes in the finger. Since a pulse oximeter probe is part of
`all portable sleep diagnostic screening devices, it is a further
`object of the present invention to tap into the received light
`intensity signal of an existing probe, thereby alleviating tbe
`need for any additional patient sensors.
`
`[0047) FIG . 3 shows a typical peripheral pulse waveform.
`Pulse height is the number of ND counts between the
`minimum and maximum excursions of each pulse, while the
`slope is also calculated in ND counts for a fixed period of
`time beginning about 40 ms after a minimum is detected.
`
`[0048) Tbe first and second derivative waveforms of the
`photoplethysmographic waveform have characteristic con(cid:173)
`tours, and the contour of the second deriva tive facilitates the
`interpretation of tbe original waves. The analysis of the
`second derivative of a llngert ip photoplethysmogTam wave(cid:173)
`form bas been shown to be a good indicator of the effects of
`vasoconstriction and vasodilation by vasoactive agents, as
`well as an index of left ventricular aftcrload as shown in
`FIGS. 4A, 48 and 4C.
`
`[0049) FIGS. 4A, 48 and 4C show waveform tracings
`demonstrating the results of administration of vasoactive
`agents. FIG. 4A shows the ECG parameter, FIG. 48 shows
`correspondi ng PTG and SOPTG waveforms, and FIG. 4C
`shows corresponding AoP and AoF waveforms. An increase
`in the .late systolic component of aortic pressure (AoP) and
`PTG after intravenous injection of 2.5 mg AGT and a
`deepened d-wave in relation to the height of the a-wave
`(decreased d/s) are seen in SDPTG. On the other band, NTG
`produces marked reduction in late systolic components of
`aortic pressu.re and PTG, wi th d-waves becoming shallower
`io rela tion to the height of a wave (increased ella). AoF
`indicates ascending aortic flow velocity. Augmentation
`index (Al) is defined as the ratio of the height of the late
`systolic peak to tha t of the early systolic peak, two compo(cid:173)
`nents of tbe ascending aortic pressure at the anacrotic notch.
`
`[0050] Selected Abbreviations and Acronyms
`
`[0051) AGT~Angiotensin
`
`[0052) AlmAugmcotation Index
`
`[0053) NTG=Nitroglyccrin
`
`[0054) PTGmPhotoplcthysmograpby
`
`[0055) SDPTG=Second Derivative Wave of Finger(cid:173)
`tip Photoplethysmography, where the a through d
`components of the second deriva tive wave are
`described io FrG . 5. The second derivative wave(cid:173)
`form consists of a, b, c, and d waves in systole and
`an e-wave io diastole.
`
`tra nsitional slope (PTS)
`[0056) Pulse
`technology as
`applied in the present invention expands on this concept of
`using photoplethysmographically derived waveforms to
`assess changes in vascular tension, whether caused by
`apnaeic obstruction or tbe more subtle rn icroarousals that are
`not detectable by cortical means. A normalized slope is
`calcu lated by dividing ihe height achieved during 40 ms of
`rise time by the maximum height of the pulse waveform
`(=height of late systolic peak). A normalized slope can be
`calculated in realtime by a microprocessor controlled device
`as opposed to tbe post processing (analysis after recording)
`required by second derivative methods. T his will allow use
`of tbe present invention technology in labs performing
`overn ight polysomnograph studies in addition
`to
`the
`intended usc for home sleep screening.
`
`[0057) Since vasoactive drugs have a distinct and predict(cid:173)
`able affect on the A1 when measured by photoplethysmo(cid:173)
`graphic methods, by extension the body's own hormonal
`control of the arterial system shows comparable changes in
`the pttlse waveform when measured using similar tech(cid:173)
`niques.
`
`[0058) The present invention provides a portable, simple,
`and cost effective sleep diagnostic method and apparatus
`capable of detecting arousals and microarousals without
`adding EEG electrodes or additional patient sensors beyond
`those worn during a typical home study.
`
`[0059) Since microarousals have been associated with
`changes in autonomic system ottlflow, an object of tbe
`present invention is to provide a small, portable device that
`analyzes the shape of the arterial fi ngcr pulse, thereby
`detecting on a beat by beat basis changes in vascular tone
`directly allributable to microarousals. The present invention
`uses a photoplethysmographically derived arterial blood
`volume waveform for monitoring change in peripheral arte(cid:173)
`rial vascula r tone in conjunction wi th AID converters and a
`microcontroller for analyzing the morphology of the pu lsa(cid:173)
`tile signal.
`
`[0060] Detection of microarousals by the present inven(cid:173)
`tion compares favorably with results achieved using pulse
`transit time (PTT) devices, EEG analysis, ECG analysis,
`esophagal pressure (Pes), and combinations of these meth(cid:173)
`ods. Although PTI' and peripheral arterial tonomet ry (PAJ)
`have both been receiving much allention as techniques fo r
`detecting changes in the ANS during s leep studies, PAl' is
`relatively expensive and PIT bas implemcotatioo problems
`caused by motion artifact.
`
`[0061) Efficacy of the present invention has been verified
`through monitoring of test subjects performing a "Valsalva
`Maneuver," which is the quickest and most dramatic me thod
`of producing ANS discharge-a resttlting increase in intra(cid:173)
`pulmonic pressure produced by forcible exhalation against
`
`012
`
`

`

`US 2004/0059236 Al
`
`Mar. 25, 2004
`
`5
`
`the closed gloHis. This produces a sympathetic discharge
`with subsequent vascular constriction.
`
`[006