Method and apparatus for noninvasive determination of peripheral arterial lumenal area

An occlusive cuff is placed around a limb (e.g. an arm) of a patient. A fluid, such as air, is pumped into the cuff, and the pressure in the cuff is measured. The pressure variation in the cuff with respect to time is caused by the pump and expansion/contraction of the arm caused by blood being pumped therethrough by the patient's heart. This variation in pressure is used to calculate systolic and diastolic pressure, artery lumen area compliance and artery volume compliance, artery lumen area, and the blood flow rate through the patient's arteries (e.g. the brachial artery for the case of the patient's arm, or the femoral artery or the case of the patient's leg).

BACKGROUND OF THE INVENTION
 This invention pertains to a non-invasive apparatus and method for
 measuring arterial compliance, arterial lumen area, the amount of blood
 flowing through the artery, and the phase lag between the pressure and
 blood flow waveforms.
 Occlusive cuffs are commonly used to measure blood pressure using the
 auscultatory method. During this method, the cuff is placed on a patient's
 arm, inflated, and gradually deflated while the attending physician relies
 on the generation of Korotkoff sounds to determine systolic and diastolic
 pressure. It is known in the art, however, that occlusive cuffs can be
 used in other ways to obtain other valuable information.
 Measuring Changes in the Volume of an Artery with an Occlusive Cuff
 Windsor, "The Segmental Plethysmograph," Angiology, Vol. 8, p. 87, 1957,
 discusses using an occlusive cuff to measure variations in the size of a
 limb (e.g. an arm). Windsor is incorporated herein by reference. FIG. 1
 illustrates Windsor's apparatus, known as a plethysmograph, which includes
 an occlusive cuff 10, a bulb 12 for pumping air into Windsor's apparatus,
 a valve 14 for isolating the apparatus from bulb 12, and a differential
 pressure chamber 16 comprising a diaphragm 18. As the volume of a
 patient's arm varies (e.g. because of blood pumped through the arm by the
 patient's heart) this variation in volume .DELTA.V can be measured with
 Windsor's apparatus using the equation
EQU Ad=K.DELTA.V
 where A is the area of diaphragm 18, d is the displacement of diaphragm 18,
 and K is a proportionality constant.
EQU K=V.sub.0 /(V.sub.0 +V.sub.1)
 where V.sub.0 is the original volume of an inactive portion 20 of Windsor's
 system, and V.sub.1 is the original volume of an active portion 22 of the
 system.
 Measuring Systolic and Diastolic Pressure with an Occlusive Cuff
 It is known in the art that one can use an occlusive cuff to measure a
 patient's systolic and diastolic pressure using the "oscillometric
 method," e.g. as described by Drzewiecki, et al., "Theory of the
 Oscillometric and the Systolic and Diastolic Detection Ratios," Annals of
 Biomedical Engineering, Vol. 22, pp. 88-96 (1994), incorporated herein by
 reference. During this method, an occlusive cuff is placed on a patient's
 arm, inflated, and slowly deflated while the cuff pressure is monitored.
 FIG. 2A illustrates cuff pressure vs. time during this method. A portion
 30 of FIG. 2A illustrates pressure while the cuff is being inflated, and a
 portion 32 illustrates pressure while the cuff is being deflated. As can
 be seen, there is a set of small ridges and valleys in the waveform of
 FIG. 2A. These ridges and valleys are caused by the expansion and
 contraction of the patient's brachial artery that occur when the patient's
 heart pumps blood through the artery.
 FIG. 2B shows the waveform of FIG. 2A after it has been band-pass filtered
 to isolate the portion of the signal between 0.5 and 5 Hz and amplified.
 This permits isolation and observation of the portion of cuff pressure
 oscillation caused by the artery expanding and contracting. As can be
 seen, the amplitude of the pulses gradually increases, reaches a maximum,
 and then decreases as the cuff deflates. The pulses of FIG. 2B are at
 their maximum amplitude when the cuff pressure equals the mean arterial
 pressure ("MAP"). One can calculate the systolic pressure as that
 pressure, above the MAP, at which the oscillation pulses have an amplitude
 As such that:
EQU As/Am=0.55
 where Am is the maximum pulse amplitude (which, as mentioned above, occurs
 when the cuff is at the MAP). In other words, the cuff pressure (above the
 MAP) which produces pulse amplitudes that equal 55% of the pulse amplitude
 at the MAP equals the systolic pressure.
 The diastolic pressure equals that cuff pressure (below the MAP) which
 produces pulses having an amplitude Ad such that:
EQU Ad/Am=0.85
 In other words, the cuff pressure (below the MAP) that produces pulse
 amplitudes that equal 85% of the pulse amplitude at the MAP equals the
 diastolic pressure.
 Using an Occlusive Cuff to Measure Artery Lumen Size
 Cuff pressure exerts a radial force on the brachial artery directed towards
 the center of the lumen of the artery As the cuff pressure decreases, the
 magnitude of the force acting on the artery directed toward the center of
 the lumen of the artery decreases. Also, as the cuff pressure increases,
 the magnitude of the force acting on the artery directed toward the center
 of the lumen of the artery increases. The difference between blood
 pressure and cuff pressure is called the "transmural pressure". The
 brachial artery exhibits compliance (i.e., elasticity) which differs with
 transmural pressure. As the cuff pressure decreases transmural pressure
 increases. Thus, the artery lumen size increases as the transmural
 pressure increases.
 If the cuff pressure exceeds the blood pressure in the brachial artery, the
 artery lumen contracts. At sufficiently high pressure (e.g. more than 200
 mm Hg), the brachial artery is pinched closed, and the lumen area is
 effectively zero. FIG. 3 illustrates the relation between an artery lumen
 area and the transmural pressure. FIG. 4 illustrates the artery compliance
 (e.g., elasticity) with respect to pressure. As can be seen, the artery is
 most compliant when the transmural pressure is zero (i.e., when the blood
 pressure in the artery equals cuff pressure). At very low transmural
 pressures and high transmural pressures, artery compliance drops.
 Pilla, "Calibrated Cuff Plethysmography: Development and Application of a
 Device For Use in Evaluation of the Effect of Arterial Pressure-Volume
 Curve Alterations on Systemic Blood Pressure," PhD. Dissertation, Rutgers
 University (May, 1995) discusses using an occlusive cuff to determine the
 pressure versus lumen area characteristics of a patient's brachial artery.
 Pilla is incorporated herein by reference. FIG. 5 schematically
 illustrates Pilla's apparatus 50. As shown in FIG. 5, apparatus 50
 includes an occlusive cuff 52 to be placed around a patient's arm (not
 shown), a pump 54 for pumping air into cuff 52, a pair of valves 56, 58, a
 pressure transducer 60, and an electrical circuit 62 for amplifying the
 signal provided by transducer 60.
 As explained below, Pilla uses pump 54 and transducer 60 to approximate the
 change in cuff volume caused by a change in pressure within cuff 52 (i.e.,
 cuff compliance). Pilla then uses this approximation of the cuff
 compliance and the pressure measured by transducer 60 to calculate the
 change in the patient's arm diameter (e.g., caused by expansion and
 contraction of the brachial artery) caused by the patient's pulse.
 Pilla begins his process by passing water through pump 54 to determine the
 stroke volume of the pump. This information is used in subsequent
 calculations of cuff compliance.
 Pilla then places valve 56 in a first position such that air from the
 atmosphere flows into an input conduit 54a of pump 54, and air from an
 output conduit 54b of pump 54 flows into cuff 52 to thereby inflate cuff
 52. After cuff 52 is inflated to a pressure in excess of the patient's
 systolic pressure, valve 56 is adjusted so that pump 54 removes air from
 cuff 52 and pumps air back into cuff 52 (e.g. as indicated by arrow A).
 Because of the manner in which valves 56 and 58 are adjusted, pump 54
 cooperates with cuff 52 to superimpose a sinusoidal pressure variation on
 the air in cuff 52.
 Transducer 60 measures the pressure in cuff 52 The pressure in cuff 52
 varies in response to two things:
 a) air being pumped in and out of cuff 52 by pump 54; and
 b) the expansion and contraction of the patient's arm caused by the
 patient's heart pumping blood through the arm. (This change in arm size is
 mostly due to expansion and contraction of the patient's brachial artery.)
 Pilla's pump has a stroke frequency of 50 to 60 Hz. The patient's heart
 beats at a frequency between 0.5 and 1 Hz. Pilla passes the output signal
 from circuit 62 to a high pass filter 63 and a low pass filter 64. High
 pass filter 63 passes signals having a frequency greater than 25 Hz,
 whereas low pass filter 64 passes signals having a frequency less than 25
 Hz. Therefore, filter 63 provides an indication of the cuff pressure
 variation caused by pump 54, whereas filter 64 provides an indication of
 the cuff pressure variation caused by the patient's heart beating.
 Pilla periodically removes air from cuff 52 via valve 58. The waveform of
 pressure vs. time provided by transducer 60 and circuit 62 is shown in
 FIG. 6. The step-like nature of the FIG. 6 waveform is caused by the
 periodic reduction in cuff pressure caused by periodically opening valve
 58. FIG. 6A shows an amplified portion of the FIG. 6 output signal. Low
 pass filter 64 receives this signal and generates in response thereto the
 signal shown in FIG. 6B, which represents that portion of the waveform
 caused by the patient's pulse. Similarly, high pass filter 63 receives the
 signal of FIG. 6 and generates in response thereto the signal of FIG. 6C,
 which represents the portion of the signal caused by pump 54. (An
 amplified version of this signal is shown in FIG. 6C'.) Pilla uses the
 output signal from high pass filter 63 to approximate the cuff compliance
 (i.e., the change in cuff volume caused by a change in cuff pressure). He
 uses the output of low pass filter 64 to determine the change in cuff
 pressure caused by the patient's pulse, and the previously approximated
 compliance value to calculate the change in cuff volume associated with
 the change in cuff pressure which is caused by the patient's pulse. This
 data is used to calculate arterial compliance and lumen area.
 One of the objects of our invention is to provide a method for determining
 the arterial compliance and lumen area using an occlusive cuff with
 improved accuracy.
 Another object of our invention is to provide a technique for continuously
 and accurately determining compliance of an occlusive cuff, and use the
 compliance to calculate arterial compliance and lumen size.
 Another object of our invention is to use a high frequency calibration pump
 and flow meter to accurately determine cuff compliance.
 Another object of our invention is to provide an improved method for
 determining artery area compliance from artery volume compliance.
 Another object of the invention is to use an occlusive cuff to obtain
 additional data such as the phase lag between the arterial blood flow
 volume pulses and arterial pressure pulses.
 SUMMARY
 A method in accordance with our invention uses an occlusive cuff to provide
 systolic and diastolic pressure, artery lumen compliance, artery cross
 section area, and blood flow in a non-invasive manner. In accordance with
 our invention, a cuff is placed around a patient's arm and inflated. A
 pump periodically pumps a fluid in and out of the cuff, and the pressure
 in the cuff is measured. The cuff pressure vs. time waveform is passed
 through a low pass filter to provide a first portion of the pressure vs.
 time waveform which is caused by the patient's pulse. The pressure vs.
 time waveform is passed through a high pass filter to provide a second
 portion of the pressure vs. time waveform which is caused by the pump
 strokes.
 Concurrently, a flow meter measures the volume of fluid pumped into and out
 of the cuff. The second portion of the pressure vs. time waveform and data
 from the flow meter are used to accurately calculate cuff compliance. The
 cuff compliance and the first portion of the pressure vs. time waveform
 are used to calculate the change in artery volume caused by the patient's
 pulse (i.e. the artery volume compliance).
 The artery volume compliance is then used to determine the artery area
 compliance. One might assume that volume compliance equals area compliance
 times cuff length. However, because of certain "edge effects" involving a
 decreased transmission of pressure from the cuff to the artery at the ends
 of the cuff, volume compliance does not exactly equal area compliance
 times cuff length. Thus, in one embodiment, we determine a "correction
 factor" to account for these edge effects. This correction factor can be
 determined by using the cuff on a test subject and measuring the test
 subject's actual artery lumen area by magnetic resonance imaging. This
 correction factor is used to calculate the artery area compliance during
 subsequent measurements taken with the cuff. The correction factor
 enhances the accuracy of the determination of artery area compliance.
 The artery area compliance is integrated to calculate the area of the
 artery lumen. The artery volume compliance is integrated to measure the
 volume of a segment of the artery.
 The derivative of artery lumen volume with respect to time is multiplied by
 the artery compliance to calculate blood flow through the artery.
 The phase lag between arterial pressure and blood flow is also determined.
 In this way, the above-mentioned parameters are non-invasively determined
 with an occlusive cuff. These parameters are important for diagnosis of
 hypertension, direct diagnosis of peripheral arterial conditions, and
 diagnosis of coronary arterial conditions based on the correlation between
 the peripheral and coronary artery conditions.

DETAILED DESCRIPTION
 Referring to FIG. 7, apparatus 100 in accordance with our invention
 comprises a pump 102, a needle valve 104, a flow meter 106, a blood
 pressure cuff 108, and a pressure transducer 110. In one embodiment, pump
 102 is a diaphragm pump with a flat line pump curve from 0 to 5 psig. In
 other words, pump 102 provides a constant known volume of gas per pump
 stroke over the relevant pressure range. (The fact that pump 102 is a flat
 line pump helps improve accuracy of our method.) In one embodiment, pump
 102 is model number 5002, manufactured by ASF Incorporated of Georgia,
 flowmeter 106 is model No. KFG-3007, available from Kobold, and transducer
 110 is model number TSD104 available from Biopak Corp. of California. The
 output signal from transducer 110 is connected to an electronic amplifier
 111 (typically model DA100, manufactured by Biopak), which in turn is
 connected to A/D converter and signal processing circuit 112.
 A motor speed control circuit 113 (typically device model no. 65DDC20-12,
 manufactured by Dart Controls, Inc.) controls the frequency of pump 102.
 In one embodiment, the frequency of pump 102 is set to be between about 20
 to 30 Hz. However, other pump frequencies can be used. A power supply 114
 (typically device no. 1HC12-3.4, manufactured by International Power,
 Inc.) provides power to motor speed control circuit 113.
 One typically begins the process by ascertaining the stroke volume of pump
 102. This can be done by measuring the volume of a fluid (e.g. a gas such
 as air) pumped by pump 102 over a period of time (e.g. ten seconds)
 divided by the number of strokes during that period of time. The fluid
 used to ascertain the stroke volume of pump 102 is typically the same
 fluid as that used to inflate cuff 108 during use of the cuff. This
 process can take place simultaneously with data acquisition and is
 monitored throughout the data acquisition procedure by using the flowmeter
 (106) and monitoring the signal received at the pressure transducer (110).
 The apparatus is then operated as follows. First, the cuff is placed
 around a patient's arm. Then, a bulb (not shown) is used to inflate cuff
 108 above the patient's systolic pressure. In one embodiment, cuff 108 is
 inflated to about 180 mm Hg of pressure. Pump 102 is then used to pump air
 in and out of cuff 108. Valve 104 is actuated to gradually reduce pressure
 in cuff 108. While this is happening, transducer 110 measures the pressure
 in cuff 108 and flow meter 106 measures the volume of air (e.g. in
 liters/minute) provided by pump 102.
 The output signal provided by transducer 106 (shown in FIG. 8) includes:
 1) a first component caused by air being pumped into and out of cuff 108 by
 pump 102; and
 2) a second component caused by the patient's heart beating.
 The first component is separately analyzed by passing the signal from
 transducer 110 through a high band pass filter. For example, in an
 embodiment in which pump 102 has a stroke rate of 20 Hz, the signal from
 transducer 110 is passed through a high band pass filter which passes
 signals between 15 and 25 Hz. FIG. 8A illustrates an output signal 118
 from the high band pass filter. The signal of FIG. 8A is essentially
 sinusoidal, with a frequency equal to the pump stroke rate.
 The second component is separately analyzed by passing the signal from
 transducer 110 through a low pass filter that passes signals having
 frequencies between 0.5 and 5 Hz, thereby generating an output signal 120.
 Output signal 120 of the low pass filter is shown in FIG. 8B. (The reason
 for the 0.5 Hz cutoff is to eliminate that portion of the pressure vs.
 time waveform caused by slightly opening valve 104.) Signals 118 and 120
 can be provided with either digital or analog filtering techniques.
 These waveforms, along with data from flow meter 106 and the frequency of
 pump 102, are used to calculate the following parameters:
 1. Systolic and diastolic pressure;
 2. Arterial compliance;
 3. Volume of blood flow through the artery per unit time;
 4. Phase lag between the pressure and blood flow waveforms;
 5. Arterial lumenal area; and
 6. Cuff compliance.
 Systolic and Diastolic Pressure
 One obtains the systolic and diastolic pressures using the technique
 described below, i.e.:
 1. Observing the size of the pulses of signal 120 to locate the cuff
 pressure corresponding to the maximum pulse size (which is the MAP).
 2. Determining the cuff pressure above the MAP at which the pulses of
 signal 120 are 55% of their maximum value (their maximum value occurs when
 the cuff is at the MAP). This pressure is the systolic pressure.
 3. Determining the cuff pressure below the MAP at which pulses of signal
 120 are 85% of their maximum value. This pressure is the diastolic
 pressure.
 Cuff Compliance
 In order to perform the remaining calculations, one determines the relation
 between cuff volume pulsations and cuff pressure pulsations caused by pump
 102. Occlusive cuffs stretch as pressure increases. This phenomenon is
 discussed by Drzewiecki, et al. in "Mechanics of the Occlusive Arm Cuff
 and Its Application as a Volume Sensor," IEEE Trans. Biomedical
 Engineering, Vol. 40, No. 7, July 1993, incorporated herein by reference.
 Thus, during a method in accordance with our invention, one calculates
 cuff compliance (referred to herein as (dV/dP).sub.pump at cuff) for each
 cuff pressure. This is calculated as follows
 1. The difference in cuff volume caused by each pump stroke (dV.sub.pump)
 is a known, constant value, measured by flow meter 106. In one embodiment,
 this can be determined since the flow rate (in volume/unit time) is
 measured by flow meter 106, and the stroke frequency of pump 102 is known.
 Flow rate divided by stroke frequency is the pump stroke volume.
 2. The difference in cuff pressure caused by each pump stroke equals the
 amplitude of signal 118 from the high pass filter.
 3. Cuff compliance (dV/dP).sub.cuff equals dV.sub.pump divided by the
 amplitude of signal 118.
 (Of importance, by using flow meter 106 and using actual measured pump
 volumes in this calculation, we continuously provide a more accurate
 measure of instantaneous cuff compliance than in the above-described Pilla
 method.)
 As will be described below, once one determines the relation between cuff
 volume changes and cuff pressure changes, one uses this information to
 determine the change in cuff volume caused by the changes in cuff pressure
 due to the patient's pulse.
 Calculation of Arterial Volume Compliance and Area Compliance
 Arterial volume compliance represents the amount that an artery expands as
 blood pressure increases. In other words, arterial volume compliance is
 the derivative of artery volume with respect to arterial pressure, and can
 be calculated as follows:
EQU (dV/dP).sub.artery =dP.sub.artery at cuff [(dV/dP).sub.pump at cuff
 /(SP-DP)]
 where SP is the systolic pressure, and DP is the diastolic pressure. SP and
 DP are calculated as described above. (dV/dP).sub.pump at cuff is the cuff
 compliance calculated as described above. dP.sub.artery at cuff is the
 amplitude of signal 120 provided by the low pass filter. Thus, all of the
 variables on the right side of the above equation are known, and therefore
 artery volume compliance is easily calculated. FIG. 4 illustrates the
 artery volume compliance of a typical artery, i.e. a graph of
 dV/dP.sub.artery vs. transmural pressure.
 From the artery volume compliance data, one can calculate the artery area
 compliance dA/dP.sub.artery as follows:
EQU dA/dP.sub.artery =dV/dP.sub.artery /(CL*CF)
 where CL is the length of cuff 108, and CF is a correction factor. One
 should use the correction factor CF because the transmission of cuff
 pressure to the artery wall is not uniform along the entire artery length.
 There is an "edge effect" of a decreased transmission at the ends of the
 cuff that leads to the correction factor. Correction factor CL is
 determined by a method described below.
 Once the term dA/dP artery is found, an arterial area compliance curve can
 be generated, e.g. as shown in FIG. 9. This curve shows the change in
 lumen area dA/dP as a function of transmural pressure.
 Calculation of Lumen Area
 Once one generates the artery area compliance curve (FIG. 9), one can
 calculate the artery lumen area by integrating to find the area under the
 artery area compliance curve. In other words, artery area A is calculated
 as follows:
EQU A=.intg.(dA/dP)dP
 This integration can be performed using numerical integration algorithms
 that are well known in the art. In one embodiment, an algorithm known as
 the trapezoidal rule is used to perform integration.
 Calculation of Correction Factor CF
 The correction factor CF for a given cuff can be obtained by using the cuff
 on a test subject, and measuring the test subject's artery lumen area by
 magnetic resonance imaging ("MRI") or other technique. The correction
 factor represents the ratio of the actual lumen area and the integral of
 dV/dP.sub.artery /CL. In other words,
EQU CF=(.intg.dV/dP.sub.artery) (CL* actual artery lumen area).
 Thereafter, the correction factor CF for that cuff can be used on other
 test subjects without recalibrating the cuff against additional MRI data
 from those other test subjects. Of importance, providing the correction
 factor enhances the accuracy of our method.
 Calculating Arterial Flow Waveform
 The oscillometric data dP/dt from filter 120 is converted to volume flow of
 blood through the artery dV/dt by multiplying dP/dt by artery volume
 compliance C=dV/dP as discussed in Whitt, et al., "Noninvasive Method for
 Measuring Flow from Oscillometric Data". However, as shown in FIG. 4,
 artery volume compliance changes with time at the differing cuff
 pressures. Therefore, the volume flow wave form is generated using the
 following equation:
EQU dV/dt=C(t)(dP/dt)+P(t) (dC/dt)
 One can compare the phase lag between blood flow and blood pressure. The
 phase lag is useful because it changes with different cardiovascular
 conditions. This is an additional variable with which to make clinical
 diagnoses.
 While the above analysis can be performed using different kinds of
 circuitry and computers, in one embodiment we connect amplifier 111 to a
 Biopak Model UTM100. The UTM100 is an interface circuit for amplified
 signals. The UTM100 is connected to a Biopak Model MP100, which is an
 analog to digital conversion interface. The MP100 is connected to an NEC
 Versa 4050C Laptop Computer running Acknowledge Software.
 Embodiment Using Multi-Bladder Cuff
 Referring to FIG. 10, an alternative embodiment of our invention comprises
 a cuff 200 comprising four bladders 202a to 202d. (Although cuff 200
 includes four bladders, other numbers of bladders can be used.) Bladders
 202a to 202d are each connected to manifolds 204a and 204b. Manifold 204a
 selectively connects one of bladders 202a to 202d to transducer 110, and
 manifold 204b selectively connects that bladder to flow meter 106, valve
 104 and pump 102.
 Each of bladders 202a to 202d is individually inflated and deflated to
 obtain the compliance and artery cross section area in the same manner as
 the one bladder within cuff 108 of FIG. 7. Compliance and artery area for
 a series of segments of the brachial artery (each segment corresponding to
 one of bladders 202a to 202d) can therefore be obtained. Of importance,
 the location of a lesion in the brachial artery can be detected by
 locating a narrowing in the artery with the multi-bladder cuff.
 In one embodiment, manifolds 204a and 204b can be connected to and
 controlled by the same circuitry used to calculate the various parameters
 discussed above.
 In yet another embodiment, each bladder is associated with its own pressure
 transducer. A selected one of the pressure transducers are connected to an
 amplifier and A/D converter via a multiplexer.
 While the invention has been described with respect to specific
 embodiments, those skilled in the art will appreciate that changes can be
 made in form and detail without departing from the spirit and scope of the
 invention. For example, cuff 108 can be placed around portions of the
 patient other than the patient's arm. Cuff 108 can be placed around the
 patient's leg to measure blood flow through and pressure within the
 femoral artery. Different types of motors, valves, pumps, flow meters, and
 computers can be used. The various calculations can be performed using
 analog or digital circuitry. Systolic and diastolic pressure can be
 obtained using the auscultatory method. Accordingly, all such
 modifications come within the invention.