CA2233865A1 - Apparatus and method for measuring an induced perturbation to determine a physiological parameter - Google Patents

Abstract

A monitor for determining a patient's physiological parameter includes a calibration device (110) configured to provide a calibration signal representative of the patient's physiological parameter. An exciter (202) is positioned over a blood vessel (220) of the patient for inducing a transmitted exciter waveform into the patient. A noninvasive sensor (210) is positioned over the blood vessel (220), where the noninvasive sensor (210) is configured to sense a hemoparameter and to generate a noninvasive sensor signal representative of the hemoparameter containing a component of a physiological parameter waveform and a component of a received exciter waveform. In this context, a hemoparameter is defined as any physiological parameter related to vessel blood such as pressure, flow, volume, velocity, blood vessel wall motion, blood vessel wall position and other related parameters. A processor (100) is configured to determine a relationship between a property of the received exciter waveform and a property of the physiological parameter. The processor (100) is connected to receive the calibration signal and the noninvasive sensor signal, and the processor is configured to process the calibration signal and the noninvasive sensor signal to determine the physiological parameter. In the preferred embodiment, the physiological parameter measured is blood pressure, however, the present invention can also be used to analyze and track other physiological parameters such as vascular wall compliance, strength of ventricular contractions, vascular resistance, fluid volum, cardiac output, myocardial contractility and other related parameters.

Description

W O 97112545 PCT~US96115820 APPA RATUS A MD M ETH O D FO R M EAS mRD~G AN nNnDUCE~D
PERTURBATION TO DETER MINE A PHYSIOLOGICAL PARAMETER

RELATED APPLICATIONS
This application is a continuation in part of the following patent appi and incorporates these applications by le~.~,..ce:
Caro, U.S. Serial No. 08/228,213 filed on April 15, 1994; and S Caro, Apparatus and Method for Measuring an Induced ~e~u,l~ation to D~Le~l-,i--e a Physiological Parameter, U.S. Provisional Applir~tisr~ Serial No.60/005,519, filed on October 3, 1995.

F~FT.n OF THE INVENTTON
The present invention relates to an apparatus and method for noninvasively providing a determ;ination of a patient's physiolo_ical parameter and other clinic~lly important parameters.

BACKGROUND OF THE INVENTION
Blood pressure is the force within the arterial syslem of an individual that ensures the flow of blood and delivery of oxygen and nutrients to the tissue.
- Prolonged reduction or loss of pressure severely limits the amount of tissue perfusion and could therefore result in damage to or even death of the tissue.
Although some tissues can tolerate hypoperfusion for long periods of time. the 20 brain, heart and kidneys are very sensitive to a reduction in blood flow. Thus, during and after surgery, blood pressure is a frequently monitored vital sign.
Blood ple...~lle is affected. during and after surgery, by the type of surgery and WO 97/lZS45 PCT/US96/15820 physiological factors such as the body's reaction to the surgery. Moreover, blood p~ u1e is manipulated and controlled, during and after surgery, using various meAi~tions. Often, these physiological factors and the given meAi~tionc can result in a situation of rapidly changing blood pressure requiring immPAi~te blood 5 pressure measurement, and corrective action.
Re~llce of changes in the patient's blood pressure, constant monitoring is important. The traditional method of me~cnring blood pressure is with a stethoscope, occlusive cuff and pressure manometer. However, this technique is slow, subjective in nature, requires the intervention of a skilled clinic~i~n and does 10 not provide timely readings frequently required in critical situations.
For these reasons, two methods of me~cl-ring blood pressure have been developed: noninvasive, intermittent methods that use an automated cuff device such as an oscillometric cuff; and invasive, continuous (beat-to-beat) measurements that use a catheter.
The oscillometric cuff method typically requires 15 to 45 seconAs to obtain a measurement, and should allow sufficient time for venous recovery. Thus, at best there is typically 1/2 to 1 minute between updated pressure measurements.
This is an inordinately long amount of time to wait for an updated p-cs~u~c reading when fast acting meAi~ations are ~Aminictered. Also, too frequent cuff inflations 20 over eYtended periods may result in ecchymosis and/or nerve damage in the area underlying the cuff. The invasive method has inherent disadvantages including risk of embolization, infection, bleeding and vessel wall damage.
To address the need for continuous, noninvasive blood pressure me~.lrelllent, several systems were developed. One approach relies on blood 25 pressure values in a patient's finger as indicative of the patient's central blood IlC, as in the cases of Penaz, U.S. Pat. No. 4,869,261 and Shim~
"Vibration Techniques for Indirect Measurement of Diastolic Arterial Pressure inHuman Fingers", Med. and Biol. Eng. and Comp. 27~2):130 (1989). Another system uses two cuffs, one on each arm, to determine calibration readings and 30 continuous readings respectively. Another system transforms a time .c~mpletl blood pl~ lllC waveform into the frequency domain and determines blood ples~.ul-, based on deviations of the fund~m~ntal frequency. Kaspari, et al. U.S. Patent Application 08/177,448, filed January 5, 1994 provides examples of these systems.

-W O 97/12545 PCTrUS96/15820 An additional class of devices, lcplGsented by L. Djordjevich et al. WO 90/00029(PCT Application), uses electrical conductance to determine blood pf,J...Ile.
A relatedl area of interest was explored by perturbing the body tissue of p~tient.~, One class of experiments causes perturbations by in~uring kinetic energy 5 into the patient, specifically, by oscillating a blood vessel. In the work of Seale, U.S. Pat. No. 4,646,754, an attempt is described to measure blood ~)lCS~7UlC: bysensing the input impedance of a blood vessel exposed to a low frequency vibration. In work by Hsu, U.S. Pat. No. 5,148,807, vibrations are used in a non-contact optical tonometer. Several experiments measured the velocity of excited 10 pel~ull,ations in the blood and demonstrated a correlation between perturbation velocity and blood pressure. Such a correlation has also been ~emon~l.,.l~
beL~eell pressure and the velocity of the natural pulse wave. However, while these studies discuss the relationship between velocity and pressure they do not ~l~ose a pr~rti~l method of me~urin~ indllcetl perturbations to determine blood p~es..Lre.
15 Exarnples of such studies are Landowne, "Characteristics of Impact and Pulse Wave Propagation in Brachial and Radial Arteries", J. Appl. Physiol. 12:91 (1958); Pruett, "Measurement of Pulse-Wave Velocity Using a Beat-Sampling Technique", Annals of Biomedical Engineering 16:341 (1988); and Amiker, ''DicpPrcion and ~ttPml~tion of Small Artificial Pressure Waves in the Canine 20 Aorta",CirculationResearch23:539(1968).
Known techniques for m~llring propagation of ples~.u~ .Lu~baLions in arteries include Tolles, U.S. Pat. No. 3,095,872 and Salisbury, U.S. Patent No.
3,090,377. Tolles employs two sensors to detect a perturbation waveform and generate two sensor signals. The two sensor signals are compared in a phase 25 detector. The phase difference of the sensor signals is displayed giving a signal that is capable of fl.~te~ting changes in blood pressure, but which does not provide a calibrated blood pressure output. Salisbury similarly employs a sensor to detect a p~Lu~ Lion waveform and generate a single sensor signal. The sensor signal is col,.paled against a reference signal. Based on the phase difference of the sensor 30 signal, a universa] formula is employed to determine the patient's blood pressure.
Since it has been shown, for PY~mple by Landowne, that the relationship between ples~.Ult; and signal propagation varies considerably from patient to patient, Salisbury's technique, based on a single formula, is not generally applicable.

QBJECTS AND SUMMARY OF THE INVENTION
The present invention describes an apparatus and method for mt~curing the inclu~ed pclLulbation of a patient's body tissue to determine the patient's blood pressure and other clinie~lly illlpo~ t parameters.
An object of the present invention is to continuously dc~ nine a patient's blood pressulc via a noninvasive sensor attached to the patient.
A related object is to induce a perturbation into a patient's blood or blood vessel and to noninvasively measure the perturbation to ~letermine the patient'sblood plc~Ulc.
A related object is to filter the noninvasive sensor signal into components including a natural component, an induced component and a noise component, and to determine the patient's blood pressure from the induced col--~one.-t.
A further related object is to determine a relationship between a plupe-ly of an induced perturbation and a pr~JCl ly of a physiological parameter.
A monitor for determining a patient's physiological p~r~meter influ~ s a calibration device configured to provide a calibration signal .ct,l~ sel.tali~/e of the patient's physiological p~r~m-~ter. An exciter is positioned over a blood vessel of the patient for inducing a tr~ncmitt~A exciter waveform into the patient. A
noninvasive sensor is positioned over the blood vessel, where the noninvasive sensor is conhgured to sense a hemoparameter and to generate a noninvasive sensor signal rcprcselll~tive of the hemoparameter containing a component of a physiological parameter waveform and a component of a received exciter waveform. In this context, a hemoparameter is defined as any physiological parameter related to vessel blood such as pressure, flow, volume, velocity, blood vessel wall motion, blood vessel wall position and other related parameters. A
processor is configured to determine a relationship between a pl~e-ly of the received exciter waveform and a p-UpCl~y of the physiological parameter. The plocessor is connected to receive the calibration signal and the noninvasive sensor signal, and the processor is configured to process the calibration signal and the noninvasive sensor signal to determine the physiological parameter. In the pler~ d embodiment, the physiological parameter measured is blood pressure, however, the present invention can also be used to analyze and track other physiological parameters such as vascular wall compliance, strength of ventricular W O 97/1Z545 PCTrUS96/15820 contractions, vascular resistance, fluid volume, cardiac output, ~llyo~dial contractility and other related parameters.

BRI~F DE~SCRIPTION OF THE FIGURES
Additional advantages of the invention will become apparent upon reading - the following ~let~iled description and upon reference to the drawings, in which:
Figure 1 depicts the present invention ~tt~hPd to a patient;
Figure 2 depicts an exciter attached to a patient;
Figure 3 depicts a noninvasive sensor ~tt~chçd to a patient;
Figure 4a depicts a blood pressure waveform;
Figure 4b depicts a blood pressure waveform with an exciter waveforrn superimposed thereon;
Figure S clepicts a schematic rli~ram of the present invention;
Figures 6a-b depict a plucessing flow chart according to one embodiment of the invention;
Figures 7a.-c are graphical illustrations of the filter L~lucedules of the present invention;
Figures 8a.-c are graphical ill~ t~tions showing the relationships between the exciter waveform and blood p,e~
Figures 9a-b depict a pl~ces~ing flow chart according to another embodiment of the invention;
Figures 10a-b depict a processing flow chart according to another embodiment of the invention;
Figure 11 depicts an exciter and noninvasive sensor ~tt~('hPJd to a patient;
and Figure 12 depicts a pressure redetermination apparatus according to an embodiment of the invention.

GLOSSARY
30 PD diastolic blood pressure PDO diastolic blood pressure at calibration Ps systolic blood pres~ule Pp pulse pressure s CA 0223386~ 1998-04-02 W O 97/12S45 PCT~US96/15820 Pw exciter waveform pressure Vd received exciter waveform V~,,, signal exciter waveform Vn noise waveform 5 V~ exciter sensor signal (tr~n~mittPd exciter waveform) Vp detected pulsatile voltage ~w exciter signal phase ~wD exciter signal phase at diastole Vel(t) exciter signal velocity 10 VelD exciter signal velocity at diastole Vels exciter signal velocity at systole DETAIL~D DESCRTPTION OF THE PREFERRED EMBODIMENTS
A ~l~felled embodiment concentrates on the physiological parameter of 15 blood pressure, however, many ~ ition~l physiologicalp~r~mPters can be measured with the present invention including vascular wall compliance, ventricular contractions, vascular resistance, fluid volume, cardiac output, myocardial contractility and other related parameters. Those skilled in the art will ~l~;iate that various changes and morlific~tions can be made to the preferred 20 embodiment while rem~ining within the scope of the present invention. As usedherein, the term continuous means that the physiological parameter of interest is determined over a period of time, such as during the course of surgery. The impl~mP~.t;.linn of portions of the invention in a digital computer is performed by sampling various input signals and pc~lro''l'ing the described procedures on a set of 2~ samples. Hence, a periodic delcll.-ination of the physiological parameter of interest is within the definition of the term continuous.
Figure 1 illustrates the components and configuration of the ~,r~rel,~d embodiment. Oscillometric cuff 110 is connected to processor 100 via wire 106, and cuff 110 is responsive to processor 100 during an initial calibration step.
30 Oscillometric cuff operation, which is known in the art, involves an automated prvcedul~ for obt~Linillg a blood pressure signal. The general procedure is given for clarity but is not cmcial to the invention.

CA 0223386F, 1998-04-02 First, an occlusive cuff is pressllri7~d around the patientjs upper arm to abate the blood ilow. Then, as the pressure is slowly reduced, a tr~n~clu(~r senses when the blood ilow begins and this pressure is recorded as the systolic p~ ule.As the ~les~u,e is further reduced, the tr~n~ducer similarly detects the plCSaLllG
S when full blood flow is restored and this pressure is recorded as the diastolic - pressure. The signals r~lcsenting pressure are delivered, via wire 106, to plocessol 100 for storage. An alternative blood pressure measurement technique such as manual or automated sphygmomanometry using Korotkoff sounds or "return to flow" techniques, could also be used. A manual measurement can be 10 provided, for example, using a keypad. Whatever measurement technique is used, a calibration device provides a calibration signal le~lcsell~tive of the patient's physiological parameter. In this respect, the calibration device is broadly defined to include automated or manual measurements.
Figure 1 shows an exciter 202 ~tt~ ed to the patient's for~ n above the 15 radial artery. Th;e exciter 202 is a device for inducing a p~lLu~lrc~ion of the patient's body tissue, and is controlled by the processor 100 via tube 107.
Figure 2 shows a cross section of the exciter and its components. The exciter 202 is an inflatable bag ~ft~ched to the processor via air tube 107. It is fixed in place near an ~cessihle artery 220 by holddown device 204 which can be 20 a buckle, adhesive strap or other device. There is also an exciter sensor 203disposed within the exciter to generate a reference signal indicative of the u-bation source waveform, and to deliver the signal to the processor via wire 108. This signal is used as a reference signal by the processor (explained below).
As mentioned above, processor 100 is attached to the exciter via tube 107.
25 The processor lO0 controls the pressure in exciter 202 with a transducer and diaphragm. A tr;ln~duc~r is a device that transforms an electric~l signal to physical movement, and a diaphragm is a flexible material attached to the tr~n~dl~cP-r for arnplifying the movement. An example of this combination is a loudspeaker. The diaphragm forms part of an airtight enclosure connected to air tube 107 and an 30 input to initi~li7~. the pressure. It will be clear to one skilled in the art that the ~n~llc~r and air tube 107 and exciter 202 can be mini~tllri7~1 and combined intoa single exciter element capable of acting as a vibrating air filled bag connected to the processor by an electrical drive signal alone, in the case that a source of CA 02233X65 l998-04-02 W O 97/12545 PCT~US96/15820 substantially constant pressure such as a spring is included in the exciter, or by an electrical drive signal and connection to a source of subst~nti~lly cons~ llC:
for the bag.
In operation, the pressure is initially established via the initi~1i7~tion inputS and then the pressure is varied by an electrical signal delivered to the tr~n~lucçr;
the diaphragm produces pressure variations in the tube in ic;~o"se to the tr~ncducer movement~ The result is that the processor, by delivering an os~illatin~
electrical signal to the tr~ncdue~r, causes osrill~ting exciter plCSSul~. The exciter responds by pc;~tulbing the patient's tissue and inducing a tr~ncmittP~ exciter waveform into the patient.
The perturbation excites the tissue 221 and blood vessel 220 below the exciter and causes the transmitted exciter waveform to radiate within the patient's body, at least a portion of which travels along the blood filled vessel. The P ~cit~ti~n waveform can be sinusoidal, square, triangular, or of any suitable shape.
E~xperiments conducted to determine a range of ~ticf~ctory l,elLull,dlion frequencies found that the range of 20-lOOOHz works well. It is ~nticir~ted thatfrequencies of lesser than 20Hz and greater than lOOOHz will also worlc well, and it is inten(l~d that this crerific~tion cover all frequencies insofar as the present invention is novel.
Figure l further shows a noninvasive sensor 210 placed at a dict~nce from the exciter on the patient's wrist. The noninvasive sensor is connected to the processor 100 via wire lO9.
Figure 3 shows a cut-away view of the noninvasive sensor 210 placed over the same radial artery 220 as the exciter. The sensor 210 is fixed in place near the artery 220 by holddown device 211 which can be a buckle, adhesive strap or otherdevice. The holddown device 211 also includes a baMe 212 to reduce noise, where the baffle is a pneumatic bag pressurized to hold the sensor 210 at a conct~nt prt;s~u~ against the patient, for example at a pressure of lOmm Hg.
,a~lt~rn~t~1y, baffle 212 can be any suitable device such as a spring or foam pad.
The noninvasive sensor 210 is responsive to at least one hemoparameter of the patient and generates a signal in response thereto. In this context, a hemoparameter is defined as any physiological parameter related to vessel blood such as pressure, flow, volume, velocity, blood vessel wall motion, blood vessel CA 0223386~ 1998-04-02 W O 97112545 PCTAJS96tl5820 wall position and other related parameters. In the preferred embodiment a piezoelectric sensor is used to sense arterial wall displacement, which is directly influenced by blood pressure.
As is shown, the sensor is positioned over the radial artery 220 and it is 5 responsive to pressure variations therein; as the pressure increases, the ~ piezoelectric m~t~ri~l deforms and generates a signal corresponding to the deformation. The signal is delivered to the processor 100 via wire 109.
Figure 1 also shows the processor 100 that has a control panel for communie~tin~ information with the user. A power switch 101 is for turning the 10 unit on. A waveform output monitor 102 displays the continuous blood pl~ llC
waveform for medical personnel to see. This waveform is scaled to the ~ U~C:~
determined by the processor, and output to the monitor. A digital display 103 informs the user of the current blood pressure; there is a systolic over rli~ctoliG and mean IJIe.;~UlC shown. A calibrate button 104 permits the user to calibrate the 15 processor at any time, by pressing the button. The calibration display 105 shows the user the blood p~ e at the most recent calibration, and also the elapsed time since calibration. The processor m~int~in.~ a record of all t~.~n~tionS that occur during patient monitoring including calibration blood ~llGS.7~11t;, calibration times, continuous blood pressure and other p~ me~ers, and it is ~nticip~t~d that ~rlfiitic)n,.l 20 information can be stored by the processor and displayed on the control panel.
Turning to the noninvasive sensor signal, in ~ lition to a natural hemoparameter, the noninvasive sensor signal contains a component indicative of the exciter waveform traveling through the patient. Although the exciter co,.,yonelll is designed to be small in col..palison to the natural hemop~ metPr, it 25 contains valuable information. Therefore, the plocessol is used to sep~ the exciter waveform from the natural hemoparameter, and to quantify the respective components to determine the patient's blood pressure.
Figure 4a slhows a natural blood pressure waveform where the minimum l~)ic;~7ell~5 the diast~lic pressure and the maximum ~ ;sen~. the systolic ~ e.
30 This waveform has a mean arterial pressure (MAP) that is a convenient reference for p.lll,oses of determining the DC offset of the waveform. Example pleS~.-Ile values are 80mm Hg diastolic and 120mm Hg systolic respectively with a MAP
DC offset of 90mm Hg.

CA 0223386~ 1998-04-02 W O 97/12545 PCT~US96/15820 Figure 4b shows an operational illustration of the arteri~l waveform; an exciter waveform superimposed on a natural blood pressure waveform. The exciter induces the exciter waveform into the arterial blood at a first location and the exciter waveform becomes superimposed on the natural waveform. Since the exciter waveform is small compared to the patient's natural waveform, the natural waveform dominates as shown in Figure 4b. As mentioned above, the noninvasive sensor signal contains information regarding both the natural waveform and the exciter waveform. The processor 100 is clç~igncd to separate the con~tituPnt components of the noninvasive sensor signal to continuously determine the patient's blood ~l~S~ G, as is discussed below.
Figure 5 depicts a schematic diagram of the preferred embodiment. There is an oscillometric cuff controller 121 for controlling the oscillometric cuff and determining the readings therefrom to generate a signal lepresenLing the patient's blood pressure. There is an induced wave frequency generator 131 coupled to a plessùl~ tr~n~ducer 133 that transforms an electrical input to a pressure output.
The tr~n~(luct~r output is conn~sted to the exciter 202 and controls the exciter's osrill~tinns for inr~uring the exciter waveform into the patient's arterial blood.
The output of the exciter sensor 203 is fed to a band pass filter 134. This filter 134 s~dles the high frequency signal responsive to the tr~ns~ cçr prt;s~ le and delivers the resulting signal to RMS meter 135 and to lock-in amplifier 143 reference input. In the p.t:r~llcd embodiment, the RMS meter output is s~mrled at a rate of 200 samples per second with a 14 bit resolution and delivered to computer 150. It is anticipated that the sampling rate and resolution can be varied with good results.
The output of the noninvasive sensor is fed to a charge amplifier 140 that delivers a resulting signal to a low pass filter 141 and a band pass filter 142.These filters sepalat~ the noninvasive sensor signal into two con~titu~nt components c;SPIltillg an uncalibrated natural blood ~ S5iUlC~ wave and a received exciter waveform respectively. The low pass filter output is sampled at a rate of 200 s~mrles per second with 14 bit resolution and delivered to computer 150, and theband pass filter output is delivered to the lock-in amplifier 143 signal input.
The lock-in amplifier 143 receives inputs from band pass filter 134 as reference and band pass filter 142 as signal, which are the exciter sensor signal CA 0223386~ 1998-04-02 (tr~n~mitted exciter waveform) and noninvasive sensor exciter signal (received exciter waveform) respectively. The lock-in amplifier uses a technique known as phase sensitive detection to single out the component of the noninvasive sensor exciter signal at a specific reference frequency and phase, which is that of theS exciter sensor signal. The amplifier 143 produces an internal, constant-~mplit~de sine wave that is :he same frequency as the reference input and locked in phase with the reference input. This sine wave is then multiplied by the noninvasive sensor exciter signal and low-pass filtered to yield a signal L,rul,o"ional to the amplitude of the noninvasive sensor signal multiplied by the cosine of the phasedifference between the noninvasive exciter signal and the ~~reience. This is known as the in-phase or real output.
The ~mplifier 143 also produces an internal reference sine wave that is 90 degrees out-of-phase with the reference input. This sine wave is multiplied by the received exciter signal and low-pass filtered to yield a signal pl~,pollional to the amplitude of the noninvasive sensor signal multiplied by the sine of the phase dirreleilce between the noninvasive sensor exciter signal and the reference. This is known as q~ rat~re or im~gin~ry output. The amplifier 143 then provides the computer lS0 with information leg~di}lg the real and im~gin~ry col~l~nellLs of the received exciter signal as referenced to the phase of the tr~ncmitt~d exciter signal.
~It~rn~tely, the amplifier can provide components ~ sPnl;n~ the m~gniturle and phase of the received exciter signal. In the preferred embodiment, the amplifieroutput is sampled at a rate of 200 samples per second with a 14 bit resolution. It is anticipated that l:he sampling rate and resolution can be varied with good results.
The computer 150 receives input from the oscillometric cuff controller 121, RMS meter 135, low pass filter 141 and lock-in amplifier 150. The computer 150 also receives input from the user interface panel 160 and is responsible for updating control pa~nel display information. The computer lS0 elrecl tt~s procedures for further s~dting constituent components from the noninvasive sensor signal and ~I~P.~ t;llg the noninvasive sensor noise component as shown in Figure 6.
VVhile the processing system described in the embodiments involves the use of a lock-in amplifier 143, it will be clear to those persons skilled in the art that similar results can be achieved by frequency domain processing. For example, a Fourier transform can be performed on the various signals to be analyzed, and W O 97/12545 PCT~US96/15820 processing in the frequency domain can be further performed that is analogous tothe described processing by the lock-in amplifier in the time domain. The various filtering steps described above can be advantageously performed in the frequencydomain. Processing steps in the frequency domain are considered as falling within - 5 the general category of the analysis of the transfer function between the exciter sensor waveform and the noninvasive sensor waveform and are int~nrled to be covered by the claims. The variety of techniques that are used in the art for the calculation of transfer functions are also applicable to this analysis.

PROCESS EXCITER WAVEFORM VELOCITY TO DETERMINE OFFSET
SCALING AND EXCITER WAVEFORM AMPLITUDE TO DETERMINE GAIN
SCALING
Figure 6 is a processing flowchart that lc;~l~sents the operation of the Figure 5 computer 150. The operation begins at step 702 with the receipt of an initial calibration measurement; noninvasive sensor signal and exciter sensor signal.
Step 704 chooses the blood ~ ssul~ waveform segment for pulse reference, which is important for continuity of measurement from pulse to pulse and for con~i~t~n~y over periods of time between calibration measurements. In this embodiment, the diastolic pressure (low-point) is chosen for purposes of simp1icity, but any point of the waveform can be chosen such as the systolic pressure or mean arterial pl'~ SUlt;
(MAP). The choice of the segment will relate to the DC offset clisc~lssed below.Step 706 is a filter step where the noninvasive sensor (received) exciter waveform is sepa,dted into signal and noise components. The noise components may have many sources, one of which is a signal derived from the exciter that travels to the noninvasive sensor by an ~ltt~rn~tç path, other than that along the artery taken by the signal of interest. E~xamples include bones conducting the exciter waveform and the surface tissue such as the skin conducting the exciter waveform. Additional sources of noise result from patient movement. Examples include voluntary patient motion as well as involuntary motion such as movement of the patient's limbs by a physician during surgery.
Figures 7a-c illustrate the principles of the received exciter signal filtering.During a natural pulse, the received exciter waveform Vd is l~lesel,ted by a collection of points that are generated in the complex plane by the real and W O 97/12~45 PCTrUS96/15820 im~gin~ry Outpults of the lock-in amplifier 143 which is monitl~ring the noninvasive sensor signal. Figure 7a l~lesents the received exciter waveform Vd in the absence of noise. In the absence of noise, Vd is the same as vector Vw(t) which has a m~nitllde and phase corresponding to the received exciter signal. During aS pulse, the m~gni~lde of VW(t) remains constant, but the angle periodically osri~l~t~s from a first angle l~lesenting a lesser pressure to a second angle ~ s~n~ a greater pl~ule. Note that in the absence of noise, the arc has a center at the origin.
Figure 7b r~l~sents the received exciter waveform Vd in the ~r~ ,enc~ of 10 noise, which is inrlir~t~i by vector Vn. Vector Vd has a m~gnitl~de and phaseaccording to the noninvasive sensor exciter waveform plus noise. As can be seen in Figures 7b-c, vector Vd(t) defines a collection of points forming an arc having a common point Vc equidistant from each of the collection of points. The vector Vw(t) from Vc to the arc corresponds to the true magnitude and phase of the 15 noninvasive signal exciter waveform. The vector Vn replesents noise and, onceid~ntifi~d, can be removed from the noninvasive sensor waveform. The filter stepremoves the Vn noise component and passes the Vw(t) signal exciter col,l~nent onto step 708.
In this embofliment, step 706 involves the arrangement of data from one or 20 more cardiac cycles in the complex plane depicted in figure 7a-c. A circle is fit to this data in the complex plane using a fitting technique such as the minimi7~tion of least-square error between the data and the fitted circle. The radius and centerlocation of the fitted circle are the adjustable parameters in this process. Once the circle that best fits the data has been determined, the m~gnitll-les of the circle 25 radius and of the vector connecting the center of the circle and the origin of the complex plane can be determined. The noise vector Vn is the vector connecting circle center and the origin. This vector can be subtracted from each data point in the complex plane. Following that operation, each data point has a m~gnitu(ie and phase, re~lcsented by the m~gnitlldç and phase of the vector connecting it to the 30 origin. These data points ~ sent the filtered signal Vw(t) and ~ t;sent the output of filter step 706.
In the above discussion, it was assumed for illustrative purposes that the m~gnitllrle of Vw(t) remains constant over the time of a pulse. In some cases the CA 0223386~ 1998-04-02 attenuation of the exciter waveform as it propagates along the artery is pl~,S~Gdependçnt, and in those cases the m~gnitllde of Vw(t) can vary during the pulse in a way that is correlated to pressure. Under such circumstances the shape of the figure traced out in the complex plane by the vector Vd will deviate from a perfect 5 circle segment. A typical shape is that of a spiral with a form that can be predicted theoretically. The functioning of this filter step under such circllm~t~n~
is conceptually similar to that described above, except that the ~-limin~tion of the noise vector Vn must involve location of the origin of a spiral rather than of the center of a circle.
Step 708 determines if the pulse is valid. To do this, the p-ocessor checks the con~ti~U~nt components of the noninvasive sensor signal to insure that the components are within acceptable clinical norms of the patient. For example, theprocessor can determine whether the new pulse is similar to the prior pulse, and if so, the new pulse is valid.
Step 720 processes the signal exciter waveform Vw(t) to determine the DC
offset. For convenience the diastole is used as the offset value, but any part of the waveform can be used. The plocessor det~.l,lines the offset when the vector Vw(t) reaches its lowest phase angle (i.e., the maximum clockwise angle of Figure 7a);this is the diastole phase angle ~w(dias). A calibration diastolic measurement is 20 stored by the processor at calibration as PDO- Also stored by the processor is a relationship denoting the relationship between the velocity of an exciter wave and blood pressure. This relationship is determined by reference to a sample of patients and is continuously updated by reference to the particular patient after each calibration mea~ult;lllellt. Figure 8a-c are graphical illustrations showing clinically 25 determined relationships between the exciter waveform and blood ples~ule. Figure 8b ltl,resell~ the relationship between phase and pressure at a frequency of l50Hz;
other frequencies have relationships that are vertically offset from the line shown.
The pressure-velocity relationship l~resents the storage of this graphical information either in a data table or by an analytical equation.
Step 721 determines the predicted diastolic pressure from the information in Step 720. The processor continuously determines the change in diastole from one pulse to the next by referencing the position of the signal exciter vector Vw(t), at ~w(dias), with respect to the stored pressure-velocity relationship. Moreover, the CA 0223386~ 1998-04-02 pressure-velocity relationship is continuously updated based on calibration measurement information gained from past calibrations of the patient.
A set of established relationships is used to develop and inte~pret information in the table and to relate the information to the sensor signal 5 co,l,~onents. First, a known relationship exists between blood p~c~s~Llre and exciter waveform velocity. Also, at a given frequency many other relationships are known: a relationship exists between velocity and wavelength, the greater the velocity the longer the wavelength; and a relationship exists between wavelengthand phase, a change in wavelength will result in a l?~o~olLional change in phase.
10 Hence, a relationship exists between blood pressure and phase, and a change in blood p,es~le will result in a plopc),lional change in phase. This is the basis for the offset predict;on.
With the ~stored calibration measurement plus the change in ~ ctolç, the new DC offset diastolic pressure is predicted PD(pred). This prediction is made 15 based on the tli~olic pressure at calibration PDO P1US the quotient of the phase difference between calibration ~WD0 and the present time ~w(dias) and the pl~s~ule-velocity relationship stored in processor memory as rate of change of exciter waveform phase to ~ u.e d(~wD)/dP.

P ( d) P (~w(d as) --~!WDO) (1) Step 722 clisplays the predicted diastolic pressure.
Step 730 determines the noninvasive sensor exciter waveform phase and velocity. This decermination is made based on the comparison of the noninvasive sensor exciter waveform with the exciter sensor waveform.
Step 731 determines the noninvasive sensor exciter waveform ~mpli~u(le 25 from the noninvasive sensor signal.
Step 732 determines the exciter waveform pressure Pw by multiplying the exciter sensor waveform m~nit~lde Ve by the ratio of the calibrated exciter waveform pleSSUlt' Pw(cal) to the calibratecl exciter sensor waveform m~gnitu-leVe(cal).

CA 0223386~ 1998-04-02 PW=V~* VW(cal) ~2) In situations where a significant pressure variation can be observed in the attenuation of the exciter waveform as it propagates from exciter to detector, an additional multiplicative pressure dependent correction factor must be included in equation 2.
Step 734 determines if the calibration values are still valid. This determination can be based on many factors including the time since the last calibration, that the linearity of the p.c~ure-velocity relationship is outside of a reliable range, determination by medical personnel that a new calibration is desired or other factors. As an example of these factors, the p~rt:lled embodiment provides user settable calibration times of 2, 5, 15, 30, 60 and 120 minutes, and could easily provide more. Moreover, the curve upon which the pressure is determined is piecewise linear with some degree of overall nonlinearity. If the processor lO0 determines that the data is unreliable because the linear region is eYcee~ed, the processor will initiate a calibration step. Finally, if the op~l~lor lS desires a calibration step, a button 104 is provided on the processor 100 for initi~ting calibration manually.
Step 736 predicts a new pulse pressure Pp(pred) by multiplying the exciter waveform pr~s~ure Pw by the ratio of the detected pulsatile voltage Vp to the dPte~t~d exciter waveform rn~gni~lde Vw.

Pp (pred) =Pw* ( vP ) 131 This prediction uses the noninvasive sensor exciter waveform to determine the pressure difference between the diastole and systole of the natural blood pressure waveform. For example, if a noninvasive sensor exciter m~nitude Vw of 0.3V relates to a pressure variation Pw of lmm Hg and the noninvasive sensor waveform Vp varies from -6V to +6V, then the noninvasive sensor waveform r~p,ese~ a pulse pressure excursion Pp(pred) of 40mm Hg.

W O 97/12545 PCT~US96/15820 Step 760 predicts a new systolic pressure P,(pred) by adding the predicted tolic PD(pred~ and pulse pressures Pp(pred).
P8 (Pred ) =PD ( p~ed ) +Pp ( pl ed ) ( 4 ) In the above example if the diastole PD(pred) is 80mm Hg (DC offset) and 5 the pulse Pp(pred) replesents a difference of 40mm Hg then the new systolic P,(pred) is 120mm Hg. Then the new systolic pressure is displayed.
For display purposes the values determined for Ps(pred) and PD(pred) can be displayed numerically. Similarly, the output waveform for display 102 can be displayed by scaling the noninvasive sensor natural blood pr~s~ c waveform prior10 to output using gain and offset scaling factors so that the output waveform has amplitude, Pp(pred), and DC offset, PD(pred), equal to those predicted in the above process. The scaled output waveform signal can also be output to other insL-uments such as monitors, computers, processors and displays to be used for display, analysis or computational input.
Step 750 is taken when step 734 determines that the prior calibration is no longer reliable as described above. A calibration step activates the oscillometric cuff 201 and determines the patient's blood pressure, as described above. The processor 100 uses the calibration measurements to store updated plcS;~ and waveform information relating to the DC offset, blood pr~ ,c; waveform and 20 exciter waveform. The updated variables include calibration pulse pressure Pp(cal), calibration exciter sensor waveform m~gnitude V~(cal), diastolic pressure PDO~
diastolic exciter waveform phase ~I?WDO, the rate of change of exciter waveform phase to pres~ure d(~wD)/dP and calibration exciter waveform plc~;~ule Pw(cal).

PW(cal) =Pp (cal) * ( VW) (S) CA 0223386~ 1998-04-02 Pl~OCESS EXCITER WAVEFORM VELOCITY TO DETERMINE OFFSET
SCALING AND GAIN SCALING
Figures 9a-b represent a modification to the previous embodiment. The initial processing steps 702, 704, 706, 708, 730 and 731 ~pl~sented in the flow chart of Figure 9 are substantially similar to those described in the previous embodiment depicted in Figure 6. In step 730, exciter waveform velocity Vel(t) and the actual phase delay of the exciter waveform ~(t) are related by the equation:

~(t) = ~0- 27rdf/Vel(t) (6) where frequency f and distance d between exciter and noninvasive sensor are known. The constant ~0 is determined in advance either analytically or empirically, and is dependent on the details of the geometry of the apparatus.
Measurement of ~(t) is generally made modulo 27r, and so the measured phase ~m(t) is related to actual phase delay by the equation:

~m(t) = ~(t) + 2n7r (7) where n is an integer also known as the cycle-number, typically in the range of 0-10. While correct deduction of propagation velocity requires a correct choice of n, a correct prediction of pressure using a pressure-velocity relation does not, so long as the same value of n is used in determining ~(t) and in determining the ples~rc-velocity relationship. In such a case, velocity should be considered as a pseudo-velocity rather than an actual measure of exciter waveform propagation speed.
In step 730, therefore, use of the ~(t) equations allows dete,lllination of the velocity, or pseudo-velocity, Vel(t) as a function of time. In step 801, the values of velocity at the systolic and fli~ctolic points of the cardiac cycle are determined as Vels and VelD. These correspond to the points of minimum and maximum phase delay or to the points of maximum and minimum amplitude of the naturally occurring blood pressure wave detected by the noninvasive sensor. Use of the -velocity relationship stored in the processor is then made to transform the values of velocity at systolic and diastolic points in time to values of pressure. In step 803 the diastolic pressure is determined using the equation:

-W O 97/12545 PCTAJS96/l5820 PD(Pred) = PDO + (VelD- VelDO)/(dVe1/dP) (8) Step 804 is p~lrol"-ed to determine the predicted systolic ~ I1G
according to the relationship:
s Ps(Pred) = PD(pred) + (Vels-VelD)/(dVel/dP) (9) In this illustration the values of Ps and PD are used to determine the U1e waveform. Similarly, other pairs of values, such as mean ple;,:~ul~ and 10 pulse pressure can also be used, and a~ ul!liate permutations of the predicted pressure equations are anticipated by this description.
In step 805 the calculated pressures are displayed as numbers, with a typical display comprising display of mean, systolic and diastolic values of thepressure waveform in digital form, together with the observed pulse rate. The 15 values of PD(pred) and Ps(pred) are used to determine a~lul,liate gain and DC offset scaling p~r~m~rs by which the naturally occurring blood pre~
waveform dete~t~d by the noninvasive sensor is scaled prior to output in step 806 as a time varying waveform, shown as 102 in Figure 1.
As in the embodiment depicted in Figure 6, step 750 involves a calibration 20 step initi~t.o~ when step 734 determines that the prior calibration is no longer reliable. During the pe~ llance of step 750 the pressure-velocity relationship is determined and stored in the processor in the form of a table or of an analytical rel~tion~hiI~. DuIing this process, it may be desirable to stop the output portion of the process as shûwn in step 752 and display a different signal, such as a blank25 screen, a dashed ]ine display, a blinking display, a square wave, or some other distinguishable signal of calibration such as an audible tone. This step is clJlGsellL~d as step 808 in Figure 9.

PROCESS EXCIl'ER WAVEFORM VELOCITY TO DETERMINE OUTPUT

In both of the previous two embodiments, values of gain Pp(pred) and offset PD(pred) are determined and used to scale the noninvasive sensor natural blood preS~ waveform to provide a time varying output waveform l~rese~ Liv~

W O 97/12545 PCT~US96/15820 of the patient's blood pressure. In this embodiment, the natural blood ~ ,s..,~
waveform monitored by the noninvasive sensor is not used in the de~ ;on of the output blood pressure waveform. As in the previous embo-liment, use is made of the rel~ti~ nchip between velocity of the exciter waveform and the blood ~ ,ule S of the patient to determine the blood pressure. Rather than making such a y~ edetermination only at the diastolic and systolic points of the cardiac cycle, exciter waveform velocity is measured many times during a cardiac cycle (typically 50 -200 times per second) and the resultant determinations of ~lc~ re are used to construct the output time varying blood pressure waveform. This process is 10 described below with ~ nce to Figure 10.
In this embodiment, the natural blood pressure waveform is not scaled.
Therefore, there is no need to sep,.rat~ the data into pulse segmentc as in step 704 of Figure 6. This feature greatly simplifies the computational task. An a~ition~l advantage of this technique is that all of the information used in the analysis 15 process is encoded in the exciter waveform, which is typically at a high frequency compared with that of both the natural blood pressure waveform and that of any artifact signals introduced by patient motion or respiration. Since all of theselower frequency signals can be removed by electronic filtering, this technique is extremely immllne to motion induced artifact and similar sources of inlelr~l~nce20 that might otherwise introduce errors into the measurement.
With the exception of this step, the initial processing steps 702,706, 731 and 730 are subst~nti~lly similar to those of previously described embodiments.
The amplitude and phase of the exciter waveform determined in step 731 are continuous functions of time. The exciter waveform phase is converted to exciter25 waveform velocity as described previously, which is also a continuous function of time.
Using a relationship between pressure and velocity, determined during or subsequent to the initial calibration and periodically redetermined, the time ~l~pendent velocity function Vel(t) is readily transformed to a time dependent 30 pressure function P(t). This transformation is l~lesellted by step 802. In a typical case, the l)les~ure-velocity relationship might be as follows:

Vel(t) = a + bP(t) (10) -CA 0223386~ 1998-04-02 W O 97112F,45 PCT~US96/15820 where the constants a and b were determined during step 750. In that case the velocity equation (10) can be used to perform the transformation of step 802.
Following a variety of checking steps, described below, that ensure the transformation used in 802 was correct, the minimllm and m~ximnm points of P(t) 5 are determined for each cardiac cycle and displayed as PD(pred) and Ps(pred) in step 805. Then, in step 806, the entire time dependent waveform is displayed as waveform 102.

DETERMINATION OF THE PRESSURE-VELOCITY RELATIONSHIP
In each of the emborlimPnt~ described thus far, an i~ ol~lt step involves the conversion of a measured phase to a dedllced exciter waveform velocity, and conversion of that value to a plcssurc. In the case of the flow chart of Figure 6, this process is integral to the calculation of the DC offset p,c. .ure PDO- In the case of the embodiment described in Figure 9, this process is integral to determin~ti-~n 15 of Ps and PD. In Ithe case of the embodiment described in Figure 10, the process is integral to the determination of plc55~11'c at each point in time for which an output value is to be displayed as part of a "continuous" plC~ UlC waveform display.
The relationship between pl~s..ulC and velocity is (lependent on many factors in~hlrlin~ the elastic p~up~ies of the artery along which the exciter 20 waveform travels. This r~i~tionship varies considerably between p~tif~.nt~, and must therefore be determined on a patient by patient basis, although a starting relationship derived from a pool of patients can be used. This determination occurs during step 750 in each of the embodiments described in Figures 6, 9, and10, and the relationship is stored in the processor in either a tabular form, or as an 25 analytical relationship. In step 734 in Figures 6, 9 and 10, a variety of parameters are examined to determine whether the system calibration continues to be acceptable. As part of that process, it is determined whether the existing pressure-velocity rel~tion~hip continues to be valid. If not, a recalibration can be initi~t~d In most patients there is a monotonically increasing relationship between 30 velocity of propagation of the induced perturbative pressure excitation along the arterial system and pressure. Over a certain range this relationship can be approximated as linear. In some cases a more complicated functional relationshipbetween pressure and velocity may need to be used. In general the rel~tion~hiI~ can CA 0223386~ 1998-04-02 W O 97fl2545 PCTrUS96/15820 be well described by an equation of order 1 or 2 and the collection of a series of (pressure, velocity) value pairs and the use of a fitting process allows the determination of an a~lupliate relationship between ples:iule and velocity. In some cases, use of a predetermined general relationship with coçffi~iPnt~ ~~ep~n~Pnt ~ S on patient pararneters such as weight, height, heart rate or age is possible.
One technique for presaul~-velocity relation determin~tion involves determination of pressure at diastolic, mean and systolic points at the substantially simultaneous time that velocity measurements are made at the same three points in the cardiac cycle. These three pairs of points can then be fit to dele~ le a pressure-velocity relationship.
In one embodiment of the pressure-velocity relationship determin~tiol-process, an occlusive cuff measurement is made on the contr~l~t~l arm (o~posite arm) to that upon which the perturbation and detection process are occurring. It is then possible to pelr("lli a conventional cuff based measurement of blood p,ci,a.lre in one arm, yielding measurement of mean, systolic and ~ tr~lic pressures, subst~nti~lly simultaneously with measurements of mean, systolic and ~ tolic velocities in the opposite arm. So long as it has been ascertained in advance that the patient has subst~nti~lly similar pressures in both arms and that the two arms are either ...~ ed at constant heights or correction is made for hydrostatic 20 ~-. saule differences between limbs, then it is valid to use the pl~aaure in one arm as a proxy for l)le~:~Ul'e in the other. In this way it is possible to obtain three pairs of pr- s~ule and velocity measurements taken during a single time interval. A
curve fitting process can be used to determine a pressure-velocity relationship that best describes this data and that relationship can be used as the basis for future 25 prediction of pleasule from measured velocity. In general it has been found that the use of a linear pressure-velocity relationship, such as in the velocity equation (10) outlined above, yields good results. In that case the fitting process yields values for the coefficients a and b.
In an alternative embodiment the cuff measurement and velocity detection 30 and ~ellull~ation can all be made on a common limb, such as a single arm. Since the process of making a cuff measurement involves occlusion of the limb, measurements of perturbation velocity during cuff pressurization yield results different to those in an unpe~lulbed limb. In one embodiment, measurements of CA 0223386~ 1998-04-02 W O 97112~45 PCT~US96/15820 velocity would be made before or after cuff inflation and the measured velocities and pressures would thus be somewhat offset in time. In a patient with stable blood pressure this may not introduce cigni~lc~n~ errors, although a typical cuff inflation time of 30-45 seconcl~ implies time offsets of that order of m~gnitllde S between the velocity and pressure measurements. In cases where this time offset introduces lln~c,eptable errors, the dele.l,dnation technique can be modified tointroduce some averaging or trending. As an example, alternating velocity and cuff blood pressure measurements could be made over a period of minutes and the results could be averaged to reduce errors due to blood l.-cs:,ure fluctuation with 10 time. Other fornns of time series manipulation familiar to one skilled in the art could be used to develop a valid relationship between blood ~le,~ulc and exciterwaveform velocity using the pairs of velocity and pressure measurements obtainedby this technique.
In a further embodiment of the pressure-velocity relationship dclel~ n 15 process, an advantage can be taken of the fact that measurement of blood ~ llC
by an occlusive cuff measurement involves a controlled and known moclifi~tit~n of the transmural ples~uie in the artery. In this embodiment, depicted in Figure 12, an occlusive cuff 811is placed over the exciter 202 and noninvasive sensor 210.
The occlusive cuff 811 can also serve the function of cuff 110 in Figure 1. The 20 pressure in cuff 811is controlled via tube 812 connected to processor 100. The exciter 202 and sensor 210 sep~r~tion and cuff size are chosen so that the exciter 202, the detector 210 and the portion of the limb between them are all covered by the cuff 811.
As the pressure in the cuff 811 is increased, the transmural pressure in the 25 artery is decreased by a known amount. Thus, during the period of cuff 811 inflation and deflation a variety of transmural pressures are experienced in theartery and a variely of velocities will be observed. Since the cuff 811 pressure is known at all times, and the end point of the cuff measurement is measurement of systolic, diastolic and mean pressure measurement, it is possible after the 30 measurement to reconstruct the value of transmural pressure at each point in time during the occlusive cuff measurement. This time series of varying transmural pl~ ~ules can then be regressed against the time series of velocities measured over the same time interval to produce a sophictic~ted and highly accurate determination of the velocity pressure relationship over a range of transmural ples~.ul~,s from zero to systolic p7le~ulc. Increased accuracy and robustness and in~.oncitivity to patient temporal pressure fluctuation can clearly be obtained by repetition of this determination and use of averaging or other time series processing to Illh~ e 5 errors due to measurement inaccuracy and to patient pressure fluctll~ti~.n.
While the velocity equation (10) is commonly adequate, in some in~t~n~es more complex functions are a~.lopliate to describe the ~lc~.ul~-velocity relationship and functional forms such as quadratic, cubic or other more co~ .lcx analytical functions can be used. In such cases the following improvement to the10 above embo-~im~on~ can be important.
In each of the pressure-velocity determination embodiments described above, only the pressure values of mean, systolic and di~tolic ples 7111'e are measured. The following improvement can be applied to each of them. The noninvasive sensor signal is filtered to provide an output r~.lt;sentative of the 15 naturally occurring blood pressure pulse as a function of time during a givencardiac cycle. Similarly, the velocity of the exciter waveform is delerl,-i,.ed as a function of time during a given cardiac cycle. By using the values of mean and diastolic and systolic pressure determined by the calibration (e.g. occlusive cuff) measurement to scale a naturally occurring blood pressure waveform measured 20 co~lel"poldneously with the cuff measurement by the noninvasive sensor, a calibrated pl~_s~lr~; waveform is determined for the blood pressure. While sensor movement and a variety of other phenomena limit the use of this calibrated waveform to a relatively short period of time, it can be used during any of the le-velocity relationship determination procedures d~s~-ribed above to yield 25 many pressure-velocity measurement pairs during a single cardiac cycle. The use of these extra points may improve the accuracy of the relationship determination, particularly in circumstances where the relationship functionality is more complex than can be described by a linear relationship, such as a nonlinear relationship.
In each of the embodiments described above, an occlusive cuff is used to 30 occlude blood flow in an artery of the patient. Other occlusive devices such as bladders, bands, pre~ n7ed plates or diaphragms can be used with equal effect.
In each of the embodiments described above, determination of the pressure-velocity relationship is made from a series of pressure-velocity pair measurements _ CA 0223386~ 1998-04-02 W O 97/12545 PCTrUS96/15820 made over a range of pressures. In general, it is possible to extrapolate this relationship outside the range of the measurements used in the de~ .n;.,A~;on. The range over which such extrapolation is valid is determined based on eY~min~tion of data from a study of multiple patients, and is related to the form of the ples~
5 velocity relationship and the values of its coefficients. The de~i~inn processembodied in step 734 in Figures 6, 9 and 10, includes an analysis of whether such extrapolation can be extended from the regime of initial calibration to that of the se.~tly measured velocity. If not, the calibration process of step 750 is initizlt~d and the de~e~ ation process described in this section is repeated.
A variety of other factors are considered in making the d~ tion as to whether a recalibration, step 750, is required. These factors include eY~min~ti~ n of the amplitude ~md phase of the exciter waveform and an çx~min~tion of their deptondence on frequency, detector-exciter separation, and on various other factors inc~ lin~ each other.
REDETERMINATION OF THE PRESSURE-VELOCITY RELATIONSHIP
Subsequent to the initial determination of the ~les ,ulc;-velocity relationship described above, it is desirable to periodically determine whether that relationship is still applicable. The relationship may become less applicable with time because 20 of physiological changes in the patient due to endogenous or exogenous ch~mi in the body that c~m affect the arterial muscular tone and, thus, the velocity of propagation of the exciter waveform. Even in the absence of changes in the patient, il"pelre~;l determination of the relationship due to measurement errors may lead to the need to check or redetermine the relationship periodically during a 25 monitoring procedure.
The determination procedures described above involve the use of an occlusive cuff. While these determin~tion procedures can be repeated periodically, there is a limit to the frequency of such measurements due to the fact that eachmeasurement results in a period on the order of a minute in which the circulation 30 of the limb is impaired. Furthermore, occlusive cuff measurement is uncomfortable and therefore it is desirable to minimi7e its use. Accordingly it is desirable for there to be a technique of redetermining the velocity pressure relationship which does not involve a conventional occlusive cuff measurement and CA 0223386~ 1998-04-02 which is relatively comfortable and pain free, which is rapid co-ilpal~d to an occlusive cuff measurement and which can be repeated frequently.
In Figures 9 and 10, this process is represented by step 901 in which the pressure-velocity relationship is periodically redetermined. The interval of such 5 redetellllination is affected by the frequency of expected changes in the relationship. This is expected to be relatively slow on the scale of the cardiaccycle and should probably be chosen to be long with respect to the lC~pildl~ly cycle to avoid interference. Time constants of the order of t = 30 seconds or more are suitable, but other time constants may also be appropliale. Subsequent to 10 each redetel-l-ination, the previously determined historical relationship is COIll~dled with the new relationship in step 902. If the relationship has changed ci~nifi~ntly, the relationship used in the determination of P1~7S~IIeiS updated in step 903. As part of this process, averaging of the variously redetermined historical relationships or other time series analysis may be used to provide increasingly accur~te 15 relationships for use as the time elapsed since the initial calibration increases.
In the embodiment of redetermination described here, a relationship of the type of the velocity equation (10) is ~Ccllm~i This technique can be generalized to other functional forms of the relationship. In the functional form of the velocity equation (10), it is neces~,.ry to determine the constants a and b corresponding to 20 the offset and slope respectively, of the relationship. In this embodiment, two separate operations are used to determine the two coefficients a and b.
To determine the relationship slope b, the embodiment depicted in Figure 12 is used. The pressure in cuff 811 is varied in accordance with a time dependent ~r~s~ function dP(t). The function dP(t) typically has the form of a square 25 wave of amplitude 10 mm Hg, period 30 - 60 seconds, and mean pressure of 5mm Hg. However, ~Itlorn~tr functional forms such as sinusoids, triangula; waves andother shapes can also be used, and larger and smaller amplitudes and offset pressures can also be used. In the example described here, the artery is subject to alternating pressures of Omm Hg and of lOmm Hg. For constant diastolic and 30 systolic P1~ 11C;S, the transmural pressures at the diastolic and systolic points, thus, alternate between (PD~ PS) and (PD-10, PS-10). The corresponding measured velorities are therefore (Vel(PD), Vel(Ps)), and (Vel(PD-10), Vel(Ps-lO)). The coefficient b can be determined using the formula:

PCT~US96/1~820 b = (Vel(Ps) - Vel(Ps-lO))/lO = (Vel(PD) - Vel(PD-lo))llo (11) Clearly, averaging over longer periods than the time constant of a single period of dP(t) leads to increased accuracy of this measurement.
S In one ernbodiment, the above technique for red~;t~;l,llillation can be used alone as a determinant of the need for the calibration step of step 750 in Figures 6, 9 and 10 to be repe~ted In an alternative embodiment, continual llr~ting of the value of b allows continual determination of the value of ~les~ e without the need for a recalibration. As an illustration, the equation:
PD(pred) = PDO + (VelD VelDO)/b ( 12) can be used at any time to predict diastolic pressure if the value of b has rem~in.oA
unchanged since the initial calibration. In the case that a is relatively constant, and that b has changed but has been continuously monitored, the prior equation can be replaced by the equation:

PD(Pre~ PDO + J' dt [[ VelD(t)--a]/b(t)]]dt ( 13) In a further embodiment of the recalibration process, the coefficient a can also be periodically redetermined. There are a number of ways to determine the offset a. In a ~ fell~d embodiment, the cuff 811 in Figure 12, is rapidly inflated to a pressure between the diastolic and systolic pressures of the last few pulses. At the time in the cardiac cycle in which cuff pressure equals or is within some determinable incrernent of intraarterial pressure, the artery will close or reopen depending on the phase of the cardiac cycle. Many signatures can be observed of this arterial closing or opening. These include Korotkoff sounds, wall motion, arterial volume monitoring, plethysmography, blood flow and electrical impe~nce In particular, it is well known to those skilled in the art that the compliance of the arterial wall becomes a maximum in a defined pressure range about zero transmural pressure, or when the cuff pressure approximates that in the artery.
There are a number of measurable indicators of this maximization of compliance CA 0223386F, l998-04-02 wO 97/12545 including wave propagation velocity and arterial displacement iri response to a pressure perturbation. Observation of the point in the cardiac cycle at which arterial wall compliance reaches a maximum thus provides a well defined signature of the point in time at which arterial pressure equals that applied eytern~lly to the artery.
The time in the cardiac cycle at which a signature appears can then be correlated with the cuff pressure in cuff 811, and the waveshape of the velocitypulses of nearby cardiac cycles can be used to associate a single velocity with a single pressure (Vell, Pl). From this pair, the value of coefficient a can be calculated using the formula Vell = a~ bP1. While this measurement of coefficient a involves application of a moderate plC;S~Ul~ to cuff 811, the ~le;7:~11G
is less than the occlusive pressure associated with a conventional blood ~res~
cuff measurement. Furthermore, the pressure need only be applied for the duration of one or at most several cardiac cycles. This is in contrast to a conventional cuff measurement in which the cuff must be fully or partially inflated over a significant number of cycles, typically of the order of 30 - 60 s~ondc This in~l~"~ eQus single value measurement can thus be made more rapidly and less tr~um~ti~lly than a multi-valued conventional occlusive cuff pressure measurement.
MULTIPLE PERTURBATIONS
For each of the different embodiments described hereto, an additional embodiment is described using multiple perturbation waveforms. All the features and advantages of the prior embodiments are applicable to these embodiments.
In the case of each of the previously described embodiments an embodiment is described in which the apparatus further induces a second exciter waveform into the arterial blood. An example second exciter waveform is one that has a frequency different from that of the first exciter waveform. It is noted that although thediscussion of the second embodiment concentrates on a second exciter wave, any number of two or more exciter waves can be used to determine the perturbation velocity measurement.
In operation, processor 100 generates two exciter waveforms and communicates the waveforms to the exciter 202 via air tube 107. The exciter 202 , CA 0223386~ 1998-04-02 responds by inducing both e~cciter wavet'orms into the patient. Noninvasive sensor 210 generates a signal responsive to a hemoparameter and transmits the signal tothe processor 100 via ~vire 109.
The processor filters the noninvasive sensor signal into c~mponents of the S natural waveform, a tlrst e~cciter waveform, a second e~citer waveform and noise.
The processor determines the phase relationship of the first e~cciter waveform to a first reference input and determined the phase relationship of the second e~cciter waveform to a second reference input.
Once the processor has determined the phase of the e~cciter waveforms, the 10 processor then generates a plurality of points, the slope of which relates to the velocity of the e~citer waveform. This is shown in Figure 8c, where the slope ofthe line is -27rd/Vel, and where d is distance and Vel is velocity. Since the distance is fixed and the slope is related to blood pressure, and since the slope changes based on changes in blood pressure, the velocity of the exciter waveform15 is determined.
The technique described above yields a measurement of the group velocity.
In contrast, the techniques described in previous embodiments result in the measurement of a phase velocity or of a pseudo-phase velocity in the case that the value of n of the phase equation (7) can not be uniquely determined. In a 20 dispersive system these values need not always agree. However, phase, group and pseudo-velocity are monotonically varying functions of pressure. Thus, a measurement of any one of the three is a basis for a pressure prediction, so long as the appropriate pressure-velocity relationship is used.
An additional benefit of the use of multiple frequency perturbations is that it 25 allows the unique determination of the value of n in the phase measurement equation described above. The unique determination of the value of n is also called resolving the cycle-number ambiguity. This allows the use of actual phasevelocity, rather than of the pseudo-velocity described earlier in the multi-perturbation analogues of the embodiments depicted in Figures 6, 9 and 10.
Once the velocity is determined, a prediction of blood pressure is made according to Figure 8a, showing the relationship of velocity to pressure. Thus, it is possible to determine the blood pressure with few, or zero, calibrations.

~j~C~
29 ~ c~

CA 0223386~ 1998-04-02 ~ nother embcdiment is depicted in ~igure 11 showing a cross section of anexciter ~0~ and noninvasive sensor 210 at the same position above the biood vessel 220. The proximate location of the exciter and the sensor permits measurement ofthe blood vessel's response to the perturbations. In this embodiment, the 5 noninvasive sensor is responsive to a hemoparameter such as blood flow or blood volume. These pararneters can be measured with a sensor such as a photoplethysmograph. Detected changes in the blood vessel due to the natural pulsatile pressure are calibrated using external ecciter pressure oscillations and compared against the sensor signal by the processor.
VARIATIONS ON THE DISCLOSED EMBODIMENTS
Additional embodiments include an embodiment in which two or more detectors are positioned along the artery at different distances from a single exciter, and an embodiment in which two or more exciters are positioned along the artery 15 at different distances from one or more detectors. In each of these embodiments, the information obtained from each exciter detector pair can be analyzed independently. The rnultiply redundant measurements of pressure that result can be combined to provide a single pressure determination that may be both more accurate and more immune from noise, motion artifact and other potential error . O . .. .
20 sources. Similar redundancy can be achieved in the embodiments that use multiple exciter waveforms by analyzing the results at each frequency independently and combining the results to provide enhanced robustness.
In addition, any combination of more than two elements (e.g. two exciters and one detector, two detectors and one exciter, one exciter and three detectors) 25 allows the value of n in the phase equation (7) to be uniquely determined so long as the spacing of two of the elements is sufficiently small to be less than a wavelength of the propagating perturbation. Since the possible range of perturbation wavelengths at a given pressure can be determined from a pool of patients, selection of the appropriate spacing is straightforward and can be 30 incorporated into the geometrical design of the device.

c~
G~

CA 0223386~ 1998-04-02 CONCLUSION
A close relationship between physiological parameters and hemoparameters supplies vaLuable information used in the present invention. The perturbation ofbody tissue and sensing the perturbation als~ supplies valuable intormation used in 5 the present invention. Although the preterred embodiment concentrates on bloodpressure, the present invention can also be used to analyze and track other physiological parameters such as vascular wall compliance, changes in the strength of ventricular contractions, changes in vascular resistance, changes in fluid volume, changes in cardiac output, myocardial contractility and other related parameters.
~alibration signals for the present invention can be obtained from a variety of sources including a catheter, manual determination, or other similar method.
The DC offset for the physiological parameter waveform can be obtained in a variety of ways for use with the present invention.
The exciter of the preferred embodiment uses air, but any suitable fluid can 15 be used. Moreover, various exciter techniques can be used for inducing an exciter waveform into the patient such as an acoustic exciter, an electromagnetic exciter and an electromechanical exciter (e.g. piezoelectric device).
Various noninvasive sensors have been developed for sensing hemoparameters. These sensor types include piezoelectric, piezoresistive, 20 impedance piethysmograph, photoplethysmograph, various types or strain gaC,es, air cuffs, tonometry, conductivity, resistivity and other devices. The present invention can use any sensor that provides a waveform related to the hemoparameter of interest.
Having disclosed exemplary embodiments and the best mode, modifications 25 and variations may be made to the disclosed embodiments while remaining within the subject and spirit of the invention as defined by the following claims.

Claims (53)

WHAT IS CLAIMED IS:

1. A monitor for determining a physiological parameter of a patient, comprising:
a calibration device configured to provide a calibration signal representative;
of one of the patient's physiological parameter;
an exciter adapted to be positioned over a blood vessel of the patient and configured to induce a transmitted exciter waveform into the patient;
a noninvasive sensor adapted to be positioned over said blood vessel and configured to sense a hemoparameter and to generate a noninvasive sensor signal containing a component of a received exciter waveform;
a processor configured to determine a relationship between a property of said received exciter waveform and a property of said physiological parameter based at least in part on said calibration signal; and wherein said processor is connected to receive said calibration signal and said noninvasive sensor signal and is configured to determine said physiologicalparameter based at least in part on said noninvasive sensor signal and said relationship.

2. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal.

3. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing one of the set of phase, amplitude, velocity and pseudo-velocity of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal.

4. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a formula Vel(t) = a + bP(t), where a is an offset variableand b is a slope variable.

5. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a formula .PHI.(t) = .PHI.0 - 2.pi.df/(a + bP(t)), where a is an offset variable and b is a slope variable.

6. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a piecewise-linear formula Vel1(t) = a1 + b1P1(t), where a1is an offset variable and b1 is a slope variable, and according to a second piecewise-linear formula Vel2(t) = a2 + b2P2(t), where a2 is an offset variable and b2 is a slope variable.

7. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a piecewise-linear formula .PHI.1(t) = .PHI.0 - 2.pi.df/(a1 + b1P(t)), where a1 is an offset variable and b1 is a slope variable, and according to a second piecewise-linear formula .PHI.2(t) = .PHI.0 - 2.pi.df/(a2 + b2P(t)), where a2 is an offset variable and b2 is a slope variable.

8. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a non-linear formula relating said transmitted exciter waveform velocity and said blood pressure and having a non-linear slope variable.

9. The monitor of claim 1, wherein:
said processor is configured to determine said relationship by comparing a property of said received exciter waveform to a property of a physiological parameter waveform.

10. The monitor of claim 1, wherein:
said processor is configured to store historical relationships between a property of said received exciter waveform and a property of said physiological parameter and configured to determine a time-related historical relationship in order to determine said relationship between a property of said received exciterwaveform and a property of said physiological parameter.

11. The monitor of claim 1, wherein:
said processor is configured to initiate a calibration to provide said calibration signal when said processor determines that said relationship is not valid.

12. The monitor of claim 1, wherein:
said processor is configured to determine said relationship based at least in part on an event that does not occlude an artery of the patient.

13. The monitor of claim 1, further comprising:
a pressure application device positioned on the same limb as said noninvasive sensor and configured to apply a pressure to said blood vessel; and wherein said processor is configured to control said pressure application device to an applied pressure less than a systolic pressure; and wherein said processor is configured to determine said relationship between a property of said exciter waveform and a property of said physiological parameter based at least in part on said applied pressure.

14. The monitor of one of claims 4, 5, 6, 7 or 8, further comprising:
a pressure application device positioned on the same limb as said noninvasive sensor and configured to apply a pressure to said blood vessel; and wherein said processor is configured to control said pressure application device to an applied pressure less than a systolic pressure; and wherein said processor is configured to determine said slope variable based at least in part on said applied pressure.

15. The monitor of claim 1, wherein:
said processor is configured to determine said relationship based at least in part on an event repeated at intervals of less than 3 minutes over an extended period of time with minimal adverse effect on the patient.

16. The monitor of claim 1, further comprising:
a pressure application device positioned on the same limb as said noninvasive sensor and configured to apply a pressure to said blood vessel; and wherein:
said processor is configured to control said pressure application device to an applied pressure less than a systolic pressure and for less than approximately 1 minute;
said processor is configured to store said applied pressure; and said processor is configured to determine said relationship based at least in part on said applied pressure.

17. The monitor of claim 4, further comprising:
a pressure application device positioned on the same limb as said noninvasive sensor and configured to apply a pressure to said blood vessel; and wherein:

said processor is configured to control said pressure application device to an applied pressure less than a systolic pressure and for less than approximately 1 minute;
said processor is configured to store said applied pressure; and said processor is configured to determine said offset variable based at least in part on said applied pressure.

18. The monitor of claim 1, wherein:
said exciter is further configured to induce a second transmitted waveform into the patient;
said noninvasive sensor signal further contains a component of a second received exciter waveform; and said processor is further configured to resolve a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

19. The monitor of claim 1, wherein:
said monitor further comprises a second noninvasive sensor positioned over said blood vessel, said noninvasive sensor configured to sense a hemoparameter and to generate a second noninvasive sensor signal containing a component of a second received exciter waveform; and said processor is further configured to resolve a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

20. The monitor of claim 1, wherein:
said monitor further comprises a second exciter positioned over said blood vessel, said second exciter configured to induce a second transmitted exciter waveform into the patient;
said noninvasive sensor is configured to generate a noninvasive sensor signal containing a component of a second received exciter waveform; and said processor is further configured to resolve a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

21. A processor for determining a physiological parameter of a patient with an apparatus having a calibration device configured to provide a calibration signalrepresentative of one of the patient's physiological parameters, an exciter adapted to be positioned over a blood vessel of the patient and configured to induce a transmitted exciter waveform into the patient, and a noninvasive sensor adapted to be positioned over said blood vessel and configured to sense a hemoparameter andto generate a noninvasive sensor signal representative of said hemoparameter, said processor comprising:
a first input configured to receive said calibration signal;
a second input configured to receive said noninvasive sensor signal;
a filter configured to separate from said noninvasive sensor signal a component representing a received exciter waveform;
a relationship routine configured to determine a relationship between a property of said received exciter waveform and a property of said physiological parameter based at least in part on said calibration signal; and a determination routine configured to determine said physiological parameter based at least in part on said noninvasive sensor signal and said relationship.

22. The processor of claim 21, wherein:
said determination routine is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device.

23. The processor of claim 21, wherein:
said determination routine is configured to determine said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device,according to a formula Vel(t) = a + bP(t), where Vel(t) is the exciter waveform velocity, P(t) is the patient's blood pressure, a is an offset variable and b is a slope variable.

24. The processor of claim 21, wherein:
said determination routine is configured to determine said relationship by comparing a property of said received exciter waveform to a property of a physiological parameter waveform.

25. The processor of one of claims 21, 22 or 23, wherein:
said processor is configured to store historical relationships between a property of said received exciter waveform and a property of said physiological parameter; and said determination routine is configured to determine a time-related historical relationship in order to determine said relationship between a property of said received exciter waveform and a property of said physiological parameter.

26. The processor of one of claims 21 or 22, wherein:
said processor is configured to initiate a calibration procedure to provide a calibration signal when said determination routine determines that said relationship is not valid.

27. The processor of one of claims 21 or 22, wherein said calibration device includes an inflatable pressure cuff adapted to be positioned on the same limb as said noninvasive sensor, and further comprising:
a control routine configured to control said inflatable cuff to an inflation pressure; and wherein said determination routine is configured to determine said relationship between a property of said exciter waveform and a property of said physiological parameter based at least in part on said inflation pressure.

28. A method of determining a physiological parameter of a patient, comprising the steps of:
providing a calibration signal representative of one of the patient's physiological parameter and storing the calibration signal;
inducing a transmitted exciter waveform into the patient;
noninvasively sensing a hemoparameter and generating a noninvasive sensor signal representative of said hemoparameter and containing a component of a received exciter waveform;
determining a relationship between a property of said received exciter waveform and a property of said physiological parameter based at least in part on said calibration signal; and processing said calibration signal and said noninvasive sensor signal to determine said physiological parameter based at least in part on said noninvasive sensor signal and said relationship.

29. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal.

30. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing one of the set of phase, amplitude, velocity and pseudo-velocity of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal.

31. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a formula Vel(t) = a + bP(t), where a is an offset variable and b is a slope variable.

32. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a formula .PHI.(t) = .PHI.0 - 2.pi.df/(a + bP(t)), where a is an offset variable and b is a slope variable.

33. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a piecewise-linear formula Vel1(t) = a1 +
b1P1(t), where a1 is an offset variable and b1 is a slope variable, and according to a second piecewise-linear formula Vel2(t) = a2 + b2P2(t), where a2 is an offset variable and b2 is a slope variable.

34. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device a said calibration signal, according to a piecewise-linear formula .PHI.1(t) = .PHI.0 -2.pi.df/(a1 + b1P(t)), where a1 is an offset variable and b1 is a slope variable, and according to a second piecewise-linear formula .PHI.2(t) = .PHI.0 - 2.pi.df/(a2 + b2P(t)), where a2 is an offset variable and b2 is a slope variable.

35. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comparing a property of said received exciter waveform to one of the set of diastolic, mean and systolic blood pressure provided by said calibration device as said calibration signal, according to a non-linear formula relating said transmitted exciter waveform velocity and said blood pressure and having a non-linear slope variable.

36. The method of claim 28, wherein:
said determining step is performed by determining said relationship by comprising a property of said received exciter waveform to a property of a physiological parameter waveform.

37. The method of claim 28, wherein:
said determining step is performed by storing historical relationships between a plurality of said received exciter waveform and a property of said physiological parameter and by determining a time-related historical relationship in order to determine said relationship between a property of said received exciterwaveform and a property of said physiological parameter.

38. The method of claim 28, further comprising the step of:
initiating said step of providing a calibration signal when said determining step determines that said relationship is not valid.

39. The method of claim 28, wherein:
said determining step is based at least in part on an event that does not occlude an artery of the patient.

40. The method of claim 28, wherein a pressure application device is positioned on the same limb as said noninvasive sensor, and wherein said method further comprises the step of:
applying an applied pressure to said blood vessel with said pressure application device; and wherein said determining step is performed by determining said relationship between a property of said exciter waveform and a property of said physiologicalparameter based at least in part on said applied pressure.

41. The method of one of claims 31, 32, 33, 34 or 35, wherein a pressure application device is positioned on the same limb as said noninvasive sensor, and wherein said method further comprises the step of:

applying a pressure to said blood vessel with said pressure application device, said applied pressure less than a systolic pressure; and wherein said determining step is performed by determining said slope variable based at least in part on said partial inflation pressure.

42. The method of claim 28, wherein:
said determining step is performed by determining said relationship based at least in part on an event repeated at intervals of less than 3 minutes over an extended period of time with minimal adverse effect on the patient.

43. The method of claim 28, wherein a pressure application device is positioned on the same limb as said noninvasive sensor, and wherein said method further comprises the step of:
applying an applied pressure to said blood vessel with said pressure application device, said applied pressure less than a systolic pressure and for less than approximately 1 minute; and wherein said determining step is performed by determining said relationship between a property of said exciter waveform and a property of said physiologicalparameter based at least in part on said applied pressure.

44. The method of claim 31, wherein a pressure application device is positioned on the same limb as said noninvasive sensor, and wherein said method further comprises the step of:
applying an applied pressure to said blood vessel with said pressure application device, said applied pressure less than a systolic pressure and for less than approximately 1 minute; and wherein said determining step is performed by determining said offset variable based at least in part on said applied pressure.

45. The method of claim 28, further comprising the step of:
inducing a second transmitted exciter waveform into the patient; and wherein said noninvasive sensor signal contains a component of a second received exciter waveform; and wherein said method further comprises the step of resolving a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

46. The method of claim 28, where a second noninvasive sensor is positioned over said blood vessel, and wherein said method further comprises the steps of:
noninvasively sensing a second hemoparameter, and generating a second noninvasive sensor signal representative of said second hemoparameter and containing a component of a second received exciter waveform; and resolving a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

47. The method of claim 28, where a second exciter is positioned over said blood vessel, and wherein said method further comprises the step of:
inducing a second transmitted exciter waveform into the patient; and wherein said noninvasive sensor signal contains a component of a second received exciter waveform; and wherein said method further comprises the step of resolving a cycle-number ambiguity based at least in part on said received exciter waveform and said second received exciter waveform.

48. A monitor for determining a patient's blood pressure, comprising:
an inflatable cuff positioned on an extremity of the patient and configured to provide a calibration signal representative of one of the patient's physiological parameter;
an exciter adapted to be positioned over a blood vessel of the patient and configured to induce a transmitted exciter waveform into the patient;
a noninvasive sensor adapted to be positioned over said blood vessel and at a distance from said exciter and configured to sense a hemoparameter and to generate a noninvasive sensor signal containing a component of a received exciter waveform;
a processor connected to receive said calibration signal and said noninvasive sensor signal including a filter configured to separate from said noninvasive sensor signal a component representing said received exciter waveform and configured to determine a relationship between a property of said received exciter waveform and a property of said physiological parameter based at least in part on said calibration signal; and wherein said processor is configured to determine said blood pressure based at least in part on said noninvasive sensor signal and said relationship.

49. The monitor of claim 48, further comprising:
an exciter sensor adapted to be positioned near said exciter and configured to sense said transmitted exciter waveform and to generate an exciter sensor signal representative of said transmitted exciter waveform; and wherein said processor is further configured to compare the phase relationship of said transmitted exciter sensor signal and said received exciterwaveform to determine said blood pressure.

50. A monitor for obtaining data of blood pressure of a patient, comprising:
a calibration device configured to provide a calibration signal representative of blood pressure of the patient;
an exciter adapted to be positioned over an artery of the patient and configured to induce a repetitive pressure wave into the patient;
a noninvasive sensor adapted to be positioned over said artery and configured to monitor a characteristic of the repetitive wave upon modification by the artery and to generate a noninvasive sensor signal representative of the modified repetitive wave;
a processor coupled to said calibration device and said noninvasive sensor and configured to determine a relationship between magnitudes of the monitored wave characteristic and blood pressure based at least in part on said calibration signal; and wherein said processor is configured to use the monitored wave characteristic and said relationship in a manner to provide the blood pressure of the patient.

51. A method of obtaining data of blood pressure of a patient, comprising:
providing a calibration signal representative of blood pressure of the patient and storing the calibration signal;
noninvasively inducing into an artery of the patient a repetitive pressure wave, noninvasively monitoring a characteristic of the repetitive wave upon modification by the artery, determining a relationship between magnitudes of the monitored wave characteristic and blood pressure based at least in part on said calibration signal, and using the monitored wave characteristic and said relationship in a manner to provide the blood pressure of the patient.

52. The monitor of claim 1, wherein:
said processor is configured to determine said relationship based at least in part on an event in which the duration of arterial inclusion is insufficient forischemia induced discomfort to occur.

53. The method of claim 28, wherein:
said determining step is based at least in part on an event in which the duration of arterial inclusion is insufficient for ischemia induced discomfort to occur.