HK1168746B

HK1168746B - System and method of measuring changes in arterial volume of a limb segment

Info

Publication number: HK1168746B
Application number: HK12109515.3A
Authority: HK
Inventors: 亚历山大．帕尔菲诺夫; 玛丽亚．帕尔飞诺瓦; 尼罗雷．康斯坦丁诺夫
Original assignee: 安其伦杰格有限公司
Priority date: 2009-05-12
Filing date: 2010-05-06
Publication date: 2015-12-11

Description

System and method for assessing arterial volume changes in a limb segment

Inventor(s):

alexander parrfonoff

Maria paler femova

Nile Comnstantinov

Cross Reference to Related Applications

According to 35USC § 119(e), the present application claims priority from us provisional application No. 61/177,341 entitled "system and method for assessing arterial volume changes in limb segments", filed 2009, 5, 12, and the entire content of which is incorporated herein by reference.

Technical Field

The present invention relates generally to assessing arterial volume changes in a limb segment.

Background

Cardiovascular disease is a major cause of morbidity and mortality. It has been demonstrated that by assessing the ability of arteries to dilate in response to increased blood flow, a diagnosis of early cardiovascular disease can be made. The degree of arterial dilation in response to increased blood flow has a correlation with cardiovascular disease severity.

Endothelial cells constitute the inner wall of blood vessels and produce nitric oxide, the major vasodilator in the arterial system. Increased blood flow increases shear forces on the endothelial cell surface, initiating signaling pathways that lead to phosphorylation and activation of nitric oxide synthase, thereby increasing nitric oxide production. In addition to being an effective vasodilator, endothelial nitric oxide blocks a number of initial steps in the pathogenesis of atherosclerotic cardiovascular disease, including the uptake of low density lipoproteins, the adhesion of leukocytes to the vessel wall, proliferation of vascular smooth muscle, and adhesion and aggregation of platelets.

The brachial artery blood flow-mediated dilation function is used as a measurement index of the bioavailability of endothelial nitric oxide of a patient, and is widely applied to large-scale clinical research of noninvasive detection of artery endothelial dysfunction.

To assess endothelial function, several interventional as well as non-invasive techniques have been developed. Interventional techniques, including coronary or brachial artery vasoactive agent perfusion, are considered the most accurate method of detecting endothelial dysfunction. The application of this technique has certain limitations in view of its high invasiveness and has led to the development of a series of non-invasive techniques. The brachial artery ultrasonic imaging technology is the most widely used noninvasive technology for evaluating vasomotor response. See, for example, j.am.call.cardiol.2002 by Mary c.coretti et al; 39: 257, 265, which are incorporated herein in their entirety. This document uses continuous Electrocardiogram (EKG) gated two-dimensional ultrasound imaging of the brachial artery before and after five minute cuff occlusion arm induced arterial dilation. The ultrasonic imaging technology is mainly applied to the evaluation of (1) brachial artery diameter change caused by the application of vasoactive drugs; and (2) blood flow-mediated vasodilation induced after occlusion of the brachial artery by inflating the cuff wrapped around the arm. Once the cuff is removed, the blood flow causes shear forces on the endothelial surface, thereby creating vasoactive substances that induce arterial dilation. Healthy people have more brachial artery diameter increase than those with endothelial dysfunction. However, even the degree of arterial dilation in healthy individuals is not sufficient to be reliably measured by ultrasound imaging techniques. A trained and experienced operating technician is necessary to obtain valuable ultrasound image data. These difficulties have limited the use of ultrasound imaging techniques to test arterial dilation to specialized vascular laboratories.

Most of the prior art is neither able to determine the amount of stimulation to which the endothelium is exposed nor to account for nitric oxide from other sources (account for), such as nitric oxide delivered or released by blood cells in response to hypoxemia caused by temporary blockage of the brachial artery. Evidence suggests that these factors can significantly affect the degree of blood flow-mediated vasodilation, thus adding additional variables to the test results obtained with instruments that fail to account for these factors.

U.S. patent No. 6,152,881(Rains et al), the entire contents of which are incorporated herein by reference, describes a method for assessing vascular endothelial dysfunction by measuring blood pressure with a pressure cuff to detect changes in arterial volume. After the artery is occluded, the pressure cuff is pressurized at near-diastolic pressure for about ten minutes until the artery returns to normal. The pressure measured during this time period is used to determine the endothelial function of the patient. The extended phase of the cuff pressure on the arm affects the blood circulation and thus the measurement process.

U.S. patent No. 7,390,303 (Dafni), the entire contents of which are incorporated herein by reference, describes a method for assessing vasodilatory and endothelial function by monitoring the cross-sectional area of the transmitting artery using bioimpedance techniques to assess the relative change in the cross-sectional area of the arterial limb. The measurement method of the bio-impedance technology is difficult to apply. Given that bioimpedance techniques require the application of electricity to the skin of a patient, the resulting skin pricking sensation is difficult for the patient to endure. Furthermore, the measured signal varies greatly.

U.S. patent nos. 7,074,193(Satoh et al) and 7,291,113(Satoh et al) describe a method and apparatus for separating partial waves from a measured blood pressure pulse wave by a fourth and nth derivative, respectively, the entire contents of which are incorporated herein by reference.

There is a clinical need for a system and method that is low cost, easy to use, non-invasive, highly acceptable to the patient, and displays the responsiveness of the artery to increased blood flow.

Disclosure of Invention

A method and diagnostic system are provided for assessing arterial volume changes in a limb segment of a mammal. In one aspect, the diagnostic system determines the amplitude of the pulse component of the measured limb segment volume pulse waves during a baseline period to determine the baseline arterial volume of the limb segment. The diagnostic system determines the amplitudes of the component pulses of the volume pulse waves of the limb segment measured during a period of time thereafter. By means of the amplitudes of the component pulses in the volume pulse waves measured during the basal period and after stimulation, the diagnostic system can determine the relative change of the arterial volume of the limb segment during the period after stimulation compared to the arterial volume of the limb segment during the basal period.

In another aspect, the diagnostic system determines the relative change in arterial volume by comparing the amplitudes of the component pulses in the volume pulse waves during the baseline period and after stimulation.

On the other hand, the pulse component is an early systolic component. In another aspect, the diagnostic system determines the relative change in arterial volume by comparing the maximum amplitude of the early systolic component of the basal-phase volume pulse waves with the maximum amplitude of the early systolic component of the stimulated volume pulse waves.

In another aspect, the diagnostic system detects the volume pulse wave of the limb segment by monitoring the limb segment during the baseline period and detects the volume pulse wave of the limb segment by monitoring the limb segment during the post-stimulation period.

The features and advantages described in the specification are not exhaustive and many other features and advantages will be apparent to those skilled in the art, particularly in light of the following drawings, specification, and claims. Moreover, it should be noted that the language used in the specification has been principally selected for readability and instructional purposes, and may not have been selected to delineate or circumscribe the inventive subject matter.

Drawings

FIG. 1 is a schematic diagram of a diagnostic system according to the present invention.

Fig. 2 is a block diagram of the diagnostic system of fig. 1.

FIG. 3 is a flow chart of the operation of the diagnostic system of FIG. 1 to perform an arterial volume change assessment.

Fig. 4 is a timing diagram of the pressure applied to the limb during the baseline testing and analysis of fig. 3 and after applying stimulation in an occlusive manner.

FIG. 5 is a timing diagram of the amplitudes of the early systolic components of the pulse waves measured during the baseline period and the post-stimulation period of FIG. 4.

FIG. 6 is a graph showing the correlation between the normalized (normalized) amplitude of the early systolic component of the pulse wave of the arm measured in some embodiments and the increase in the brachial artery diameter measured by the brachial artery ultrasound imaging.

Fig. 7 is a timing diagram of blood flow and systolic pressure after the occlusion release of fig. 4.

Figures 8a and 8b are enlarged timing diagrams of oscillations in measured cuff pressure in the limb during one inflation/deflation cycle before occlusion and after removal of a vascular occlusion in the limb of figure 4, respectively.

Figure 9 is a timing diagram of the pressure applied to the limb during the basal test and analysis of figure 3 and the detection and analysis after stimulation by oral nitroglycerin.

Fig. 10 is a timing chart showing the amplitudes of the early systolic component waves in the pulse waves measured in the basal period, the stimulation period, and the post-stimulation period in fig. 9.

FIG. 11 is a flow chart of one embodiment of performing the arterial volume change assessment of FIG. 3.

FIG. 12 is a flow chart of one embodiment of determining amplitude during an assessment of arterial volume change in FIGS. 3 and 11.

Fig. 13 is a timing chart of the measured pulse wave of a healthy person.

FIG. 14 is a timing diagram of measured pulse waves of a cardiovascular disease patient.

FIG. 15 is a flow chart of one embodiment of determining the change in arterial volume during the operations of FIGS. 3 and 11.

Detailed Description

A preferred embodiment of the present invention will be described with reference to the accompanying drawings. In the drawings, like reference numbers can indicate identical or functionally similar elements. In the figures, the left-most digit(s) of a reference number corresponds to the figure in which the reference number is first used.

Fig. 1 is a schematic diagram of a diagnostic system 100 according to the present invention. The diagnostic system 100 includes a diagnostic device 102, a diagnostic computer 104, a cuff 106, a Doppler sensor 108, and a blood oxygen saturation level (StO)₂) A sensor 110.

In the present application, the volume pulse wave is a blood pressure oscillation between the systolic and diastolic blood pressure. The diagnostic system 100 detects volume pulse waves and performs a diagnosis based on the detected pulse waves to assess arterial volume changes in a limb segment. In some embodiments, the volume pulse wave includes a composite pulse wave formed by superposition of a plurality of pulse partial waves. These pulse components are partially overlapped, and the waveform or contour of the arterial pulse wave is formed by the superposition of these pulse components. The pulse components may include, for example, incident systolic waves (also known as early systolic waves), reflected waves (also known as late systolic waves), and other waves. The diagnostic system 100 monitors changes in arterial volume of the limb segment after the application of the stimulus by measuring the amplitude of the component waves in the arterial volume pulse wave. However, it may be easier to measure the amplitude of the whole (whole) arterial volume pulse wave, the timing of the pulse component waves may drift (shift) throughout the test, and the waveform of the pulse wave may change. In some embodiments, the diagnostic system 100 measures the amplitude of physiologically significant components of the volume pulse wave (e.g., pulse components) to assess arterial volume changes in the limb segment. The diagnostic system 100 can employ any pulse component or portion thereof (e.g., peak, inflection point, or amplitude at a fixed point in time) of the measured volume pulse waves, any portion of the volume pulse waves (e.g., peak, inflection point, or amplitude at a fixed point in time) or a combination thereof to assess arterial volume change. As an example, the operation of the diagnostic system 100 to measure early systolic pulse waves is described herein.

In use, the cuff 106 is wrapped around the limb 120 such that when the cuff 106 is inflated, the cuff 106 compresses a section of the limb 120. It will be appreciated by those skilled in the art that the measurement of arterial volume changes in a limb segment described herein does not measure the volume change of a single artery in the limb 120, but rather measures the volume change of almost all arteries in the limb 120 that are under compression. Although only one arterial volume change measurement and the physiological conditions therein have been described, it will be appreciated by those skilled in the art that the present invention is not limited to a single artery and that the volume change measurement is a measurement of the volume change of all or substantially all arteries in the limb segment being measured. The limb 120 may be any limb or extremity thereof, but for the sake of brevity, the limb 120 is described as the upper arm and the artery being evaluated is described as the brachial artery. In some embodiments, the limb 120 is a leg and the artery is a femoral artery. Although the diagnostic system 100 is described for use with a human, the invention is not so limited. The diagnostic system 100 may be applied to other mammals.

The diagnostic computer 104 provides control signals to the diagnostic device 102 while accepting information from the diagnostic device 102 and data from the test examination.

The diagnostic device 102 inflates and deflates the cuff 106 via the tube 112 on the cuff 106. The diagnostic device 102 may control, detect, and monitor the air pressure in the conduit 112. In some embodiments, other gases besides air, or some liquid such as water, may be used for the cuff 106, the tube 112, and the pneumatic module 202 (see FIG. 2). In some embodiments, the cuff may be an electronically controlled elastomer or a mechanically controlled material.

Although the diagnostic system 100 is described herein as applying pressure to the limb 120 via the cuff 106 to occlude the artery 122, other forms of stimulation may be suitable as well, as blood flow into the artery 122 may be induced to stimulate the endothelium after the occlusion is released. In various embodiments, the stimulation of the endothelium includes mechanical, thermal, chemical, electrical, neural, mental, or physical motor stimulation, or any combination thereof, to induce changes in arterial volume of the limb segment. These stimulation means are well known, some of which induce nitric oxide production by endothelial cells on the inner wall of the artery. In some embodiments, any manner of transient local increase in blood flow and shear forces on the inner wall of the artery may also produce stimulation of the endothelium. This can be achieved, for example, by applying ultrasound to create turbulence in the aorta. The chemical stimulus may be, for example, a vasoactive agent such as oral nitroglycerin, or upper arm acetylcholine infusion.

The diagnostic device 102 communicates the doppler sensor 108 and the oxygen saturation level (StO)₂) The sensors 110 provide control signals and receive measurement signals from them. Doppler sensor 108 and blood oxygen saturation (StO)₂) The sensor 110 is used in some embodiments to determine the amount of vasodilatory stimulation, such as a transient occlusion of an artery of a limb segment.

The doppler sensor 108 is positioned on the limb 120 adjacent to an artery 122 of the limb 120 and either distal to the cuff 106 or proximal to the cuff 106 to measure the blood flow rate in the artery 122 using a doppler process (process). The doppler sensor 108 may be any conventional doppler sensor that may be designed to measure the rate of blood flow in a transmitting artery. In some embodiments, the diagnostic system 100 does not include the doppler sensor 108.

Blood oxygen saturation (StO)₂) Sensor 110 is positioned on limb 120, remote from cuff 106, to measure blood oxygen content in limb tissue to determine oxygen saturation of hemoglobin in the tissue. The blood oxygen saturation (StO)₂) The sensor 110 may be any conventional StO₂A sensor. In some embodiments, the diagnostic system 100 does not include oxygen saturation of blood (StO)₂) A sensor 110.

Although the doppler sensor 108 and the blood oxygen saturation sensor 110 are described herein as one means of determining the amount of stimulation produced by occlusion, other means for determining the amount of vasoactive stimulation may be suitable.

Although the diagnostic computer 104 is described herein as performing the operations of controlling, calculating, and analyzing in the diagnostic system 100, the invention is not so limited. The diagnostic device 102 may include a processor or microcontroller to perform any or all of the operations described herein as being executed by the diagnostic computer 104.

Although the diagnostic computer 104 is described herein as being located on the diagnostic device 102, the diagnostic computer 104 may be connected to the diagnostic device 102 via a communication line, system, or network, such as the internet, wireless, or wired. For example, the operation of the diagnostic device 102 may be performed in the vicinity of the patient, while the diagnostic computer 104 may perform remote data processing.

Fig. 2 is a block diagram showing the diagnostic apparatus 102. The diagnostic device 102 includes a pneumatic module 202, a pressure detector 204, a Doppler sensor system 206, and blood oxygen saturation (StO)₂) A sensor system 208, and an interface 210. The pneumatic module 202 is responsive to control signals from the diagnostic computer 104 to control the pressure in the cuff 106. The pneumatic module 202 includes a pump 222 (e.g., an air pump) to pressurize air, a reservoir 224 to store the pressurized air, and a pressure controller 226 to control the bleeding off of air that is inflated to the cuff 106 through the tube 112.

The pressure detector 204 includes a pressure sensor electronics 228 to control a pressure sensor 230 that senses the pressure in the cuff 106 through the conduit 112. The pressure sensor 230 detects pressure oscillations in the cuff 106 caused by the arterial 122 pulse wave. In some embodiments, the pressure sensor 230 is placed on the cuff 106 or the catheter 112. In some embodiments, pressure sensor 230 is a plethysmographic sensor, such as a reflective photoplethysmographic sensor.

The interface 210 is connected to the diagnostic computer 104, the pneumatic module 202, the pressure detector 204, the Doppler sensor system 206, and the blood oxygen saturation level (StO)₂) The sensor system 208 transmits control signals and information signals therebetween. Interface 210 may comprise a processor or microcontroller to perform any or all of the operations described herein.

The doppler sensor system 206 is in communication with the doppler sensor 108 for measuring the velocity of blood flow in the artery 122. In some embodiments, the diagnostic computer 104 instructs the doppler sensor system 206 to measure the blood flow rate in the artery 122 after the cuff pressure is released to assess the amount of stimulation due to the shear forces experienced by the artery 122.

In some embodiments, the diagnostic computer 104 may be provided with blood flow rate test data and may use the test data to determine the amount of stimulation the patient receives after the occlusion has been removed. The diagnostic computer 104 may use this data as part of the arterial volume change assessment of the limb segment described herein.

Blood oxygen saturation (StO)₂) Sensor system 208 and blood oxygen saturation (StO)₂) The sensor 110 is in communication to measure the blood oxygen content in the tissue to determine the oxygen saturation of hemoglobin in the blood of the tissue.

In some embodiments, diagnostic computer 104 may be provided with blood oxygen saturation test data and may use these test data to normalize the degree of ischemia in a limb of a plurality of subjects and determine the amount of stimulation a particular patient receives after removal of an occlusion. The diagnostic computer 104 may use this data as part of the arterial volume change assessment of the limb segment described herein.

Fig. 3 is a flow chart of the operation of the diagnostic system 100 to perform an arterial volume change assessment. Prior to operation of the diagnostic system 100, the cuff 106 is wrapped around a limb 120 (e.g., upper arm) of the patient. The test may be initiated by logging onto diagnostic computer 104 in any known manner, such as by using keys on a keyboard (not shown) or by moving a cursor and selecting keys on a screen via a mouse (not shown). In response to the initiation of a diagnostic instruction, the diagnostic computer 104 assesses the change in arterial volume of a segment of the limb 120. The diagnostic computer 104 performs a basal period test and analysis (block 302) during a basal period 402 (see FIG. 4, below). In some embodiments, the diagnostic system 100 detects and analyzes volume pulse waves of a segment of the limb 120 during a baseline period in which no stimulus is applied to the patient. In some embodiments, the volume pulse wave analysis includes determining a measured volume pulse wave amplitude to calculate a base arterial volume of the segment of the limb 120. One embodiment of the basal period test is described below in conjunction with FIG. 4.

During a stimulation period 404 (see fig. 4 below), a stimulation is applied to the patient to induce a change in arterial volume for a period of the segment of the limb 120 (block 304). In some embodiments, the diagnostic computer 104 instructs the pneumatic module 202 to pressurize the cuff 106 to a degree sufficient to occlude the artery 122. In some embodiments, the cuff 106 is inflated above the systolic pressure for a period of time sufficient to induce a change in arterial volume of the segment of the limb 120 upon release of the cuff pressure.

The diagnostic computer 104 performs post-stimulation testing and analysis (block 306) during a post-stimulation period 406 (see fig. 4, below). In some embodiments, the diagnostic system 100 detects and analyzes a volume pulse wave of a segment of the limb 120 after a stimulus (e.g., a predetermined time after the stimulus is applied at the beginning or at the end). In some embodiments, the volume pulse wave analysis includes determining the amplitude of the early systolic component of the measured volume pulse wave to calculate the arterial volume of the segment of the limb 120 after stimulation. One embodiment of the post-stimulation test is described below in conjunction with fig. 4. The analysis in blocks 302 and 306 may be performed separately from the testing and at a later time.

The diagnostic computer 104 performs an arterial volume change assessment (block 308). In some embodiments, the diagnostic computer 104 calculates the relative change in arterial volume of the limb 120 during the post-stimulation period 406 (see FIG. 4) as compared to the baseline period 402 (see FIG. 4) by the amplitude of the early contraction component of the volume pulse wave during the baseline period and post-stimulation. One embodiment of arterial volume change assessment is described below in conjunction with fig. 15.

In some embodiments, the hypoxemia level (or oxygen saturation) assessment may be included in the arterial volume change assessment (block 308) and implemented by any method that is compatible with the testing process (e.g., measuring hypoxemia based on a non-pulsatile (non-pulsatile) method if the artery is occluded with the cuff 106). In some embodiments, the blood flow velocity or blood shear force assessment after the removal of the occlusion may be included in the arterial volume change assessment (block 308) and implemented by any method that is compatible with the detection process (e.g., based on Doppler measurement methods).

Fig. 4 is a timing diagram of the pressure applied to the limb 120 during the baseline testing and analysis (block 302), and the post-stimulus application testing and analysis (block 306) of fig. 3 in an occlusive manner. Prior to performing the procedure of FIG. 4, the patient's blood pressure is measured to select an integrated pressure to apply to his limb. During blood pressure measurement, the diagnostic system 100 may determine systolic, diastolic, and mean arterial pressures in a conventional manner. Once the blood pressure measurement is completed, the individualized pressure exerted on the patient's limb may be determined as a percentage of the diastolic, or systolic, or mean arterial pressure. The individualized pressure may also be determined by a formula based on the blood pressure of the patient. For example, the pressure applied to the patient's limb may be calculated from the patient's diastolic blood pressure minus 10 mm Hg. By normalizing the pressure applied to each patient, the test data for patients with different blood pressures can be compared.

As an illustrative example, during the baseline 402 (e.g., 150 seconds), the diagnostic device 102 measures the resting arterial volume pulse wave of the brachial artery 122, thereby indicating the resting diameter of the brachial artery 122. During the baseline 402, the diagnostic system 100 instructs the diagnostic device 102 to perform a series of rapid inflations 412 and deflations 414 of the cuff 106 and instructs the diagnostic device 102 to collect data from the pressure sensor 230. (for clarity only 10 inflations 412 and 10 deflations 414 are shown, but other times may be suitable. for clarity only one inflation/deflation cycle is labeled.) in each cycle, the cuff is rapidly inflated 412 to a pressure, such as sub-diastolic arterial pressure, then remains inflated 416 for a predetermined period of time (e.g., 4 to 6 seconds), and then remains deflated 418 for a predetermined period of time (e.g., 4 to 10 seconds). In some embodiments, the diagnostic computer 104 may dynamically determine the duration of the inflation status 416 and the number of pulses based on the measurement process. When the cuff 106 is in the inflated state 416, the diagnostic device 102 may detect a plurality of pressure oscillations (or volume pulse waves).

Following the baseline period 402, the diagnostic device 102 inflates the cuff 106 to a supra-systolic pressure (e.g., 50 mm Hg above systolic pressure), thereby temporarily occluding the artery 122 to enter the occlusion period 403 (e.g., approximately 300 seconds). At the same time as the block, the blood oxygen saturation (StO)₂) Sensor electronics 208 controls blood oxygen saturation (StO)₂) A sensor 110 to monitor the degree of hypoxemia in the limb remote from the occlusion cuff。

During the stimulation period 404 thereafter, the diagnostic device 102 rapidly releases the pressure in the cuff 106 (e.g., to a pressure below venous pressure, such as 10 mm hg below venous pressure) to allow blood flow into the limb 120. Releasing the pressure in cuff 106 causes a rapid increase in blood flow in artery 122, thereby creating shear forces on the endothelium of brachial artery 122. This shear force stimulates the endothelial cells to produce Nitric Oxide (NO), thereby dilating the artery 122.

With the cuff deflated, the doppler sensor electronics 206 controls the doppler sensor 108 to collect data during the time period (e.g., 10-180 seconds) that the doppler sensor 108 is measuring the blood flow rate.

During the post-stimulation period 406, the diagnostic system 100 instructs the diagnostic device 102 to rapidly inflate 422 and deflate 424 the cuff 106 in a series and instructs the diagnostic device 102 to collect data from the pressure sensor 230 over a predetermined time (e.g., 1 to 10 minutes) in a manner similar to that during the baseline period 402. (for clarity only 14 inflations 422 and 14 deflations 424 are shown, but other times may be suitable. for clarity only one inflation/deflation cycle is labeled.) in each cycle, the cuff is rapidly inflated to a certain pressure and remains inflated 426 for a predetermined period of time (e.g., 4 to 6 seconds), and then remains deflated 428. In some embodiments, the diagnostic computer 104 may dynamically determine the duration of the inflation state 426, as well as the number of pulses detected, based on the measurement process. During this time, the diagnostic computer 104 monitors the dynamic changes in arterial volume of the limb segment (the pulse wave amplitude gradually increases to a maximum value and then gradually decreases back to a resting state).

Fig. 5 is a timing diagram of the amplitudes of the early systolic components of the pulse waves measured during the baseline period 402 and the post-stimulation period 406 of fig. 4.

FIG. 6 is a graph of the correlation between the normalized amplitude of the early systolic component of the measured brachial volumetric pulse wave and the measured increase in brachial artery diameter from brachial artery ultrasound imaging, in some embodiments. Each data point in the graph corresponds to a different patient. The stimulation applied in both methods was done by 5 minutes occlusion of the brachial artery after inflation of the cuff to supra-systolic pressure. The normalization of the test results obtained in the present invention illustrates the fact that the diagnostic system 100 evaluates the change in volume of almost all arteries in a limb segment, while ultrasound images only image the aorta.

Fig. 7 is a timing diagram of blood flow and systolic pressure during stimulation period 404 after the blockage of fig. 4 is released. Curve 701 shows a sharp increase in blood flow followed by a drop to normal flow. Curve 702 shows a temporary drop in systolic pressure after the block has been removed.

Fig. 8a and 8b are magnified time charts of measured oscillations in cuff pressure in the limb 120 during one inflation/deflation cycle of the blood vessel in the limb 120 before occlusion (fig. 8a) and during one cycle after the occlusion is removed (fig. 8 b). In the cuff pressure sequence, data relating to cuff pressure oscillations due to brachial artery pulsation is collected. The change in oscillation amplitude (or pulse wave amplitude) correlates with the change in brachial artery radius, and fig. 8b shows that the pulse wave amplitude after occlusion removal is greater than the pulse wave amplitude before occlusion.

In some embodiments, the arterial volume pulse wave is detected using external pressure applied to the segment of the limb 120. In some embodiments, the external pressure applied varies gradually between a near-systolic pressure and a near-diastolic pressure. In some embodiments, the external pressure is applied starting at the near-systolic pressure and then gradually decreasing to the near-diastolic pressure. In some embodiments, the external pressure is applied starting at the near-diastolic pressure, gradually increasing the pressure to the near-systolic pressure at a rate that allows oscillations to be detected, and then rapidly decreasing the pressure.

In some embodiments, as shown in fig. 4 and 9, the applied external pressure cycles between a high pressure and a low pressure such that an arterial volume pulse wave can be determined when the external pressure is at the high pressure. In some embodiments, the high pressure is below diastolic pressure and the low pressure is below venous pressure.

In some embodiments, the high voltage 416 or 426 lasts no more than 10 seconds in any cycle. In some embodiments, the low voltage 418 or 428 lasts at least 4 seconds in any cycle. In some embodiments, the measurement is continued for at least one cardiac cycle.

Fig. 9 is a timing diagram of the pressure applied to the limb 120 during the basal period testing and analysis (block 302) and the post-oral nitroglycerin stimulation testing and analysis (block 306) of fig. 3. Because there is no blocking period 403, the diagnostic system 100 performs a series of rapid inflations 422 and deflations 424, and maintains the inflated state 426, and measures the volume pulse wave during the basal period 402, the stimulation period 404, and the post-stimulation period 406.

Fig. 10 is a timing diagram of the amplitude of the early systolic component of the pulse waves measured in the basal period 402, the stimulation period 404, and the post-stimulation period 406 of fig. 9.

FIG. 11 is a flow chart illustrating one embodiment of performing an arterial volume change assessment (FIG. 3 block 308). In response to initiation of a diagnostic command by the user, the diagnostic computer 104 assesses changes in arterial volume of a segment of the limb 120. As described above in connection with fig. 4-8 (or fig. 9-10, depending on the type of stimulation), the diagnostic device 102 detects volume pulse waves of the limb segment during the baseline 402 (block 1102). In some embodiments, the diagnostic computer 104 instructs the pneumatic module 202 to pressurize the cuff 106 to a degree sufficient for the pressure detector 204 to detect a volume pulse wave of a segment of the limb 120.

The diagnostic device 102 determines the amplitude of the early systolic component of the measured volume pulse wave (block 1104). In some embodiments, the diagnostic computer 104 instructs the pressure detector 204 to detect the volume pulse wave of the segment of the limb 120. The diagnostic computer 104 analyzes the waveform of the measured volume pulse waves and determines the relative amplitude of the basal period volume pulse waves. In one embodiment, the relative amplitude of the pulse wave is the difference between the highest pressure and the lowest pressure in the pulse wave. In some embodiments, the correlation amplitude is the amplitude of the early compressional wavelet. One embodiment of determining the amplitude at block 1104 is described below in conjunction with FIG. 12 (blocks 1102 and 1104 may be used for block 302 in FIG. 3).

The diagnostic device 102 applies a stimulus during the stimulation period 402 to induce a change in arterial volume for a period of the segment of the limb 120 (block 1106). In some embodiments, the diagnostic computer 104 instructs the pneumatic module 202 to pressurize the cuff 106 to a degree sufficient to occlude the artery 122 (block 1106 may be used for block 306 in FIG. 3; other stimulation modality embodiments are described above in connection with FIGS. 1 and 9-10).

The diagnostic device 102 detects the volume pulse wave for the segment of the limb 120 at the post-stimulation period 406 to detect changes in arterial volume of the limb as described above in connection with fig. 4-8 (block 1108). In some embodiments, the diagnostic computer 104 instructs the pneumatic module 202 to pressurize the cuff 106 sufficiently to enable the pressure detector 204 to detect a volume pulse wave of a segment of the limb 120.

The diagnostic device 102 determines the amplitude of the early systolic component of the volume pulse waves measured after stimulation (block 1110). In some embodiments, the diagnostic computer 104 instructs the pressure detector 204 to detect the volume pulse wave of the segment of the limb 120. The diagnostic computer 104 analyzes the measured volume pulse wave waveforms and determines the relative amplitudes of the basal period volume pulse waves. In one embodiment, the relative amplitude of the pulse wave is the difference between the highest pressure and the lowest pressure of the pulse wave. In some embodiments, the correlated amplitude is the amplitude of the early systolic component. One embodiment of determining the amplitude at block 1110 is described below in conjunction with FIG. 12 (blocks 1108 and 1110 may be used at block 306 in FIG. 3).

The diagnostic device 102 performs an arterial volume change assessment (block 1112). In some embodiments, the diagnostic computer 104 calculates the relative change in arterial volume of the limb 120 during the post-stimulation period 406 as compared to the baseline period 402 by the amplitude of the early systolic component of the volume pulse wave during the baseline period and after stimulation. In some embodiments, the diagnostic computer 104 calculates the relative change by comparing the amplitudes of the early systolic components in the volume pulse wave during the baseline period (block 1104) and after stimulation (block 1106). (block 1112 may be used for block 308 in fig. 3). One embodiment of the arterial volume change assessment will be described below in conjunction with fig. 15.

FIG. 12 is a flow diagram of one embodiment of determining an amplitude when performing an arterial volume change assessment (block 308 in FIG. 3 and block 1112 in FIG. 11). The diagnostic computer 104 determines the amplitude of the early systolic component of the pulse wave by computing the fourth derivative of the measured volume pulse wave (block 1202). The diagnostic computer 104 determines the point in time at which the fourth derivative crosses the neutral line a third time (block 1204) (third neutral crossing 1322 in fig. 13, below, and third neutral crossing 1422 in fig. 14, below), in some embodiments, the diagnostic computer 104 may instead determine the measured volume pulse wave second derivative. In some embodiments, the diagnostic computer 104 may instead determine an inflection point in the volume pulse wave and employ the point in time at which the inflection point occurs. In some embodiments, the diagnostic computer 104 may instead perform a fourier transform on the volume pulse wave to determine the point in time at which the pulse wave component peak occurs.

The diagnostic computer 104 determines the pressure value of the measured volume pulse wave at the point in time (block 1206). The diagnostic computer 104 determines the pressure value at the onset of the volume pulse wave (block 1208). In some embodiments, the diagnostic computer 104 determines the pressure value at the beginning of the volume pulse wave by determining the diastolic minimum value of the pulse wave. The diagnostic computer 104 assesses the amplitude of the early systolic component of the volume pulse wave as the difference between the pressure values (block 1210).

In some embodiments, the diagnostic computer 104 may calculate other order derivatives in the operations of block 1202, or may not calculate derivatives, but instead determine inflection points corresponding to the early systolic component wave peaks of the pulse wave in other ways. In other embodiments, the diagnostic computer 104 may determine the arterial volume pulse wave maximum amplitude.

FIG. 13 is a timing chart of the pulse waves measured for a healthy person. The pulse wave 1300 includes an early systolic component wave 1302 and a late systolic component wave 1304. (the pulse wave 1300 may include other pulse wave components not shown.) the early systolic component 1302 forms an inflection point 1310 in the pulse wave 1300. Because of the amplitude and timing of the late systolic component 1304, the maximum of the pulse wave 1300 coincides with the peak of the early systolic component 1310. Line 1320 is the fourth derivative of the pulse wave 1300, which includes a third zero crossing 1322. This intersection 1322 is used to determine the time and amplitude 1312 of the early systolic wavelet division.

During the post-stimulation period, the waveform of the arterial volume pulse wave changes to a pulse wave 1350. The pulse wave 1350 includes an early systolic component wave 1352 and a late systolic component wave 1354. (the pulse wave 1350 may include other pulse wave components not shown.) the early systolic component 1352 forms an inflection point 1360 in the pulse wave 1350. During the post-stimulation period, the amplitude and timing of the late systolic component 1352 changes slightly, and the maximum 1366 of the pulse wave 1350 no longer completely coincides with the peak of the early systolic component 1360. However, the amplitude 1362 of the early systolic component wave 1352 is slightly different from the amplitude of the maximum 1366 of the pulse wave 1350 (interval 1362 plus interval 1364).

FIG. 14 is a timing chart of the measured pulse wave of a patient with cardiovascular disease. The pulse wave 1400 includes an early systolic component 1402 and a late systolic component 1404. (the pulse wave 1400 may include other pulse wave components not shown.) the early systolic component 1402 forms an inflection point 1410 in the pulse wave 1400. Because of the amplitude and timing of the late systolic component 1404, the maximum of the pulse wave 1400 and the peak of the early systolic component 1410 are completely coincident. Line 1420 is the fourth derivative of the pulse wave 1400, which includes a third zero crossing 1422. This intersection 1422 is used to determine the time and amplitude 1412 of the early systolic wavelet division.

During the post-stimulation period, the waveform of the arterial volume pulse wave changes to pulse wave 1450. The pulse wave 1450 includes an early systolic component wave 1452 and a late systolic component wave 1454. (the pulse wave 1450 can include other pulse wave components not shown.) the early systolic component wave 1452 forms a knee 1460 in the pulse wave 1450. During the post-stimulation period, the amplitude and timing of the late systolic component wave changes significantly, and the maximum 1466 of the pulse wave 1450 no longer coincides with the peak of the early systolic component wave 1460. The amplitude 1462 of the early systolic component wave 1452 is significantly different from the amplitude (interval 1462 plus interval 1464) of the maximum 1466 of the pulse wave 1450.

The diagnostic system 100 may calculate an arterial index (e.g., an augmentation index) based on the differences in the pulse wave characteristics in fig. 13-14 to assess the cardiovascular status of the patient.

Fig. 15 is a flow chart of one embodiment of determining a change in arterial volume during the operations of fig. 3 and 11. The diagnostic computer 104 calculates the average pulse wave amplitude for each inflation/deflation cycle during the measurement and obtains a graph, such as the one described above in connection with fig. 5.

The diagnostic computer 104 calculates an Average (AVG) of the calculated average amplitudes of the early systolic components of the pulse waves measured in the basal phase 402_{Basal period}) (block 1502). For the post-stimulation period 406, the diagnostic computer 104 calculates a curve that fits the post-stimulation data for the early systolic component of the pulse waves measured at the post-stimulation period 406 (block 1504), as may be done with a fourth order polynomial function. The diagnostic computer 104 calculates the maximum value (MAX) of the curve fitted to the post-stimulation data_{After stimulation}). The diagnostic computer 104 calculates the time from the end of the occlusion (or other stimulus) to the maximum in the fitted curve of post-stimulus data (block 1508). The diagnostic computer 104 calculates the relative amplitude change from the basal period to the maximum in the fitted curve of the post-stimulation data (block 1510).

The diagnostic computer 104 calculates the relative change in arterial volume Δ V (block 1512) as follows:

ΔV＝[(MAX_{after stimulation}-AVG_{Basal period})/AVG_{Basal period}]

The diagnostic computer 104 calculates the relative change in arterial radius as follows (block 1512):

ΔR＝[(ΔV+1)^1/2-1]，

the relative change in radius Δ R is defined as follows:

ΔR＝[(R_{after stimulation}-R_{Basal period})/R_{Basal period}]，

Wherein R is_{After stimulation}Is the maximum value of the radius of the artery after stimulation, R_{Basal period}Is the basal artery radius.

In some embodiments, the diagnostic computer 104 may calculate the post-stimulation data fitted curve area in addition to, or as an alternative to, performing the operation of determining the maximum of the fitted curve in block 1506. In some embodiments, the diagnostic computer 104 calculates the area of the curve by integrating the time period from the end of the stimulation to when the measured amplitude returns to the basal period level or the end of the test for which the polynomial function was fitted in block 1504. In some embodiments, the diagnostic computer 104 extrapolates the fitted curve in block 1504 to the point where the measured amplitude returns to the base phase level. In some embodiments, the diagnostic computer 104 calculates the relative change in arterial volume by calculating other parameters (e.g., half-peak width) of the fitted curve in block 1504.

The diagnostic computer 104 may provide any or all of the raw and processed data to a physician or clinical researcher via a display, paper, or other means known to those skilled in the art. In some embodiments, the diagnostic computer 104 provides the physician with processed data such as, for example, 1) the relative percent change in arterial volume in the limb segment following stimulation (e.g., a 57% change in arterial volume after 5 minutes of cuff occlusion) to reflect the ability of the artery to dilate in response to the stimulation; 2) calculating the relative maximum percentage change of the artery radius after stimulation; the time to maximum change in arterial volume (e.g., 72 seconds); 4) area of the curve; and 5) pulse wave characteristics (time difference of early and late systolic wave peaks, augmentation index, etc.) as an indicator of arterial stiffness. In some embodiments, the diagnostic computer 104 provides the physician with raw data, such as the volume pulse wave measured during each inflation/deflation cycle.

Although the diagnostic system 100 described herein includes one cuff 106, other numbers of cuffs 106 may be suitable. In some embodiments, the diagnostic system 100 includes two cuffs 106. A cuff 106 is placed over the limb 120 and blocks the artery 122; the other cuff 106 is placed on the limb 120 away from the first cuff 106 and pressure oscillations are detected. Alternatively, a cuff 106 is placed on the limb 120 to detect the arterial 122 pressure; another cuff 106 is positioned on the limb 120 distal to the first cuff 106 and blocks the artery 122.

Reference in the specification to "some embodiments" means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least one embodiment of the invention. The appearances of the phrase "in some embodiments" in various places in the specification are not necessarily all referring to the same embodiments.

The following detailed description is directed to algorithms and symbolic representations of data bits within a computer memory. These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is here, and generally, conceived to be a self-consistent sequence of steps (instructions) leading to a desired result. The steps are those requiring physical manipulations of physical quantities. Usually, though not necessarily, these quantities take the form of electrical, magnetic, or optical signals capable of being stored, transferred, combined, compared, and otherwise manipulated. For convenience, these signals are sometimes referred to as bits, values, elements, symbols, characters, terms, numbers, or the like, based primarily on conventional usage. Moreover, it is sometimes convenient, and not uncommon, to refer to a particular means of physically manipulating a physical quantity as a module or as an encoding device.

However, all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. Unless specifically stated otherwise as apparent from the following discussions, it is appreciated that throughout the specification discussions utilizing terms such as "processing" or "computing" or "calculating" or "determining" or "displaying" or "determining" or the like, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system memories or registers or other information storage, transmission or display devices.

Certain aspects of the present invention comprise processing steps and instructions presented herein in the form of an algorithm. It should be noted that the process steps and instructions of the present invention could be in software, firmware or hardware form, and when in software form, could be downloaded to be stored and operated on different platforms used by different operating systems.

The invention also relates to a device for running an operation. This apparatus may be specially constructed for the required purposes, or it may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer. Such a computer program may be stored in a computer readable storage medium, such as, but is not limited to, any type of disk including floppy disks, optical disks, CD-ROMs, magnetic-optical disks, read-only memories (ROMs), Random Access Memories (RAMs), EPROMs, EEPROMs, magnetic or optical disks, Application Specific Integrated Circuits (ASICs), or any type of media suitable for storing electronic instructions, and each coupled to a computer system bus. Further, the computers described in this specification may include a single processor, or an architecture that employs a multi-processor design for increased computing power.

The algorithms and displays presented herein are not inherently related to any particular computer or other apparatus. Various general-purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct more specialized apparatus to perform the required method steps. The required structure of the various systems is as follows. Furthermore, the present invention is not limited to a particular programming language. Various programming languages may be used to implement the teachings of the invention as described herein, and any references to specific languages below are intended to disclose the invention and provide the best mode.

Although specific embodiments of, and applications for, the invention are described herein, the invention is not to be limited to the precise construction and components disclosed herein. Various modifications, changes and substitutions in the arrangement, operation and details of the method and apparatus of the invention may be made without departing from the spirit and scope of the invention as defined by the appended claims.

Claims

1. A method of assessing change in arterial volume of a limb segment of a mammal, the method comprising:

determining an amplitude of a component pulse wave of the measured volume pulse waves of the non-limb portion of the measured limb segment during a basal period to determine a basal arterial volume of the limb segment;

applying a stimulus to the mammal to induce a change in arterial volume of the limb segment over a period of time;

determining an amplitude of a component of a measured volume pulse wave of a non-limb portion of the limb segment measured over a period of time after a stimulus is applied to the mammal to induce a change in arterial volume of the limb segment over a period of time; and

determining the relative change of the arterial volume of the limb segment in the post-stimulation period compared to the arterial volume of the limb segment in the basal period by the amplitudes of the pulse components in the volume pulse waves measured during the basal period and after stimulation;

wherein determining the relative change in arterial volume of the limb segment comprises:

calculating the average pulse wave amplitude in the basal period;

generating a curve fitting pulse wave amplitude of a period after stimulation;

calculating the maximum value of the fitted curve;

determining the time between the starting point of the post-stimulus period and the time point of the maximum of the fitted curve;

determining the relative amplitude change from the basal period to the maximum of the fitted curve;

and determining the relative change of the arterial volume by the relative amplitude change from the basal phase to the maximum of the fitted curve and the mean pulse partial wave amplitude of the basal phase.

2. The method of claim 1, wherein the pulse component is an early systolic component.

3. The method of claim 2, wherein

Determining the relative change in arterial volume comprises comparing the maximum amplitude of the early systolic component of the volume pulse waves during the basal phase with the maximum amplitude of the early systolic component of the volume pulse waves after stimulation.

4. The method of claim 2, wherein

Determining the amplitude of the early systolic component of the volume pulse wave comprises:

determining the occurrence of a volume pulse wave inflection point;

determining a time point at which an inflection point occurs;

determining a pressure value on the volume pulse wave measured at the time point;

determining a pressure value of a starting point of the volume pulse wave; and

the amplitude of the early contraction partial wave in the volume pulse wave is evaluated as the difference between the pressure values.

5. The method as recited in claim 1, further comprising:

monitoring the limb segment during a basal period to record volume pulse waves measured by non-extremity portions of the limb segment;

the limb segment is monitored over a period of the post-stimulation period to record volume pulse waves measured by the non-extremity portion of the limb segment.

6. The method of claim 5, wherein the pulse component is an early systolic component.

7. The method according to claim 1, wherein the stimulation comprises mechanical stimulation, thermal stimulation, chemical stimulation, electrical stimulation, neural stimulation, mental stimulation, or physical motor stimulation or any combination thereof to induce changes in arterial volume of the limb segment.

8. The method of claim 1, wherein applying the stimulus comprises inflating a cuff positioned on the limb segment above systolic pressure for a period of time sufficient to induce a change in arterial volume of the limb segment upon release of the cuff inflation pressure.

9. The method of claim 8, further comprising:

monitoring blood oxygenation in a limb segment remote from the cuff to normalize limb ischemia levels in a plurality of test subjects; and

quantifying the amount of stimulation experienced by a particular patient in response to the normalized degree of limb ischemia in the plurality of test subjects.

10. The method of claim 1, wherein calculating a basal-phase mean pulse wave amplitude comprises:

determining an average pulse wave amplitude for each of a plurality of inflation/deflation cycles of a basal period; and

the mean pulse wave amplitude of the basal period is calculated from the mean pulse wave amplitudes of the plurality of inflation/deflation cycles.

11. The method of claim 1, wherein generating a curve fit pulse wave amplitude comprises generating a fourth order polynomial function to fit post-stimulation pulse wave amplitude.

12. The method of claim 1, wherein determining the relative change in arterial volume of the limb segment further comprises integrating the area of the fitted curve from the end of the stimulation to the time when the measured amplitude returns to the baseline amplitude.

13. A method of assessing change in arterial volume of a limb segment of a mammal, the method comprising:

monitoring a limb segment during a basal period to record volume pulse waves measured by non-extremity portions of the limb segment;

monitoring the limb segment during a post-stimulation period after the application of the stimulus to record volume pulse waves measured by non-extremity portions of the limb segment;

determining the amplitude of a component pulse wave in the measured volume pulse wave of the non-limb portion of the limb segment measured during the post-stimulation period; and

determining the relative change of the arterial volume of the limb segment in the post-stimulation period compared with the arterial volume of the limb segment in the basal period by the amplitudes of the pulse components in the volume pulse waves measured in the basal period and the post-stimulation period;

wherein monitoring the limb segment during both the basal and post-stimulation periods comprises:

applying a series of external pressures on the limb segment at the limb segment mean arterial pressure; and is

A non-extremity partial volume pulse wave of the limb segment is detected.

14. A method of assessing change in arterial volume of a limb segment of a mammal, the method comprising:

external pressure is applied to the limb segment at a pressure level that causes blood flow through the artery to generate the volume pulse wave in response to the applied external pressure.

15. The method of claim 14, wherein applying the external pressure comprises

Gradually changing the external pressure between a near-systolic pressure and a near-diastolic pressure, and

a volume pulse wave is detected when the external pressure is between the systolic pressure and the diastolic pressure.

16. The method of claim 14, wherein applying the external pressure comprises:

the external pressure is applied starting from a pressure close to the systolic pressure, and

the external pressure is gradually reduced to a pressure near the diastolic pressure.

17. The method of claim 14, wherein applying the external pressure comprises:

the external pressure is applied starting from a pressure close to the diastolic pressure, and

the external pressure is gradually increased to a pressure near the systolic pressure.

18. The method of claim 14, wherein applying the external pressure comprises: cycling the external pressure between a high pressure and a low pressure, wherein determining the amplitude of a component of a volume pulse wave comprises said determining when the external pressure is at the high pressure.

19. The method of claim 18, wherein the high pressure is near mean arterial pressure and the low pressure is below venous pressure.

20. The method of claim 18, wherein the high pressure is below diastolic pressure and the low pressure is below venous pressure.

21. A method of assessing change in arterial volume of a limb segment of a mammal, the method comprising:

wherein the pulse wave component is an early systolic component;

wherein determining the amplitude of the early systolic component of the volume pulse wave comprises:

calculating the fourth derivative of the measured volume pulse wave;

determining a time point of the fourth derivative crossing the zero line for the third time;

determining a pressure value of a starting point of the volume pulse wave; and

22. The method of claim 21 wherein determining a pressure value for a starting point of the volume pulse wave comprises determining a minimum value of the pulse wave corresponding to a single diastole.

23. A diagnostic system for assessing changes in arterial volume of a limb segment of a mammal, comprising:

a sensor for detecting a non-extremity partial volume pulse wave of a limb segment in a basal period and detecting the non-extremity partial volume pulse wave of the limb segment during a period of arterial volume change after stimulation;

a processor coupled to the sensor for determining an amplitude of a component of the measured volume pulse wave in the measured volume pulse wave of the non-limb portion of the measured limb segment during a basal period to determine a basal arterial volume of the limb segment, for determining an amplitude of a component of the measured volume pulse wave of the non-limb portion of the limb segment measured during a period after a period of time of change in arterial volume of the limb segment caused by the application of a stimulus to the mammal, and for determining a relative change in arterial volume of the limb segment during the period after the stimulus as compared to the basal period from the amplitudes of the component of the measured volume pulse wave during the basal period and after the stimulus;

wherein the processor calculates a baseline mean pulse wave amplitude, generates a curve fitting the pulse wave amplitude of the post-stimulation period, calculates a maximum value of the fitted curve, determines the time from the start of the post-stimulation period to the time point of the maximum value of the fitted curve, determines the relative amplitude change from the baseline to the maximum value of the fitted curve, and determines the relative change in arterial volume by the relative amplitude change from the baseline to the maximum value of the fitted curve and the baseline mean pulse wave amplitude, thereby determining the relative change in arterial volume of the limb segment.

24. The diagnostic system of claim 23, wherein the processor determines the relative change in arterial volume by comparing the amplitudes of the component pulses in the volume pulse waves during the baseline period and after the stimulus.

25. The diagnostic system of claim 23, wherein the pulse component is an early systolic component.

26. The diagnostic system of claim 25 wherein the processor determines the relative change in arterial volume by comparing the maximum amplitude of the early systolic component of the basal-phase volume pulse waves to the maximum amplitude of the early systolic component of the stimulated volume pulse waves.

27. The diagnostic system of claim 25, wherein the processor determines the occurrence of an inflection point in the volume pulse wave, determines a point in time at which the inflection point occurs, determines a pressure value on the volume pulse wave measured at the point in time, determines a pressure value at the beginning of the volume pulse wave, and assesses the amplitude of the early systolic component waves in the volume pulse wave as the difference between the pressure values to determine the amplitude of the early systolic component waves in the volume pulse wave.

28. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor for applying pressure to the limb segment to occlude an artery of the limb segment and releasing the pressure applied to the limb segment to induce blood flow in the artery for a period of time to induce a change in arterial volume of the limb segment in response to control signals from the processor.

29. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor for applying a stimulus to the mammal to induce a period of arterial volume change in the limb segment.

30. The diagnostic system of claim 23, further comprising a pressure cuff coupled to the sensor and the processor for applying stimulation to the mammal by: inflating to a pressure above systolic to apply pressure to the limb segment for a time sufficient to induce a change in arterial volume of the limb segment upon release of the cuff inflation pressure.

31. The diagnostic system of claim 30, further comprising:

a blood oxygen sensor coupled to the processor for monitoring a segment of the limb remote from the cuff for normalizing a degree of limb ischemia in a plurality of test subjects; and

wherein the processor quantifies an amount of stimulation experienced by a particular patient in response to the normalized degree of limb ischemia in the plurality of test subjects.

32. The diagnostic system of claim 23 wherein the processor determines a mean pulse wave amplitude for each of a plurality of inflation/deflation cycles of a basal period and calculates a mean pulse wave amplitude for the basal period from the mean pulse wave amplitudes for the plurality of inflation/deflation cycles to calculate the mean pulse wave amplitude for the basal period.

33. The diagnostic system of claim 23 wherein the processor generates a fourth order polynomial function to fit post-stimulation pulse wave amplitudes to generate curve-fit pulse wave amplitudes.

34. The diagnostic system of claim 23, wherein the processor integrates the area of the fitted curve from the end of the stimulation to the time when the measured amplitude returns to the baseline amplitude to determine the relative change in arterial volume of the limb segment.

35. A diagnostic system for assessing changes in arterial volume of a limb segment of a mammal, comprising:

a processor coupled to the sensor for determining an amplitude of a component of the measured volume pulse wave in the measured volume pulse wave of the non-limb portion of the measured limb segment during a basal period to determine a basal arterial volume of the limb segment, for determining an amplitude of a component of the measured volume pulse wave of the non-limb portion of the limb segment measured during a period after a period of time of change in arterial volume of the limb segment caused by the application of a stimulus to the mammal, and for determining a relative change in arterial volume of the limb segment during the period after the stimulus as compared to the basal period from the amplitudes of the component of the measured volume pulse wave during the basal period and after the stimulus; and

a pressure cuff coupled to the sensor and the processor for applying stimulation to the mammal by: inflating to a pressure above systolic to apply pressure to the limb segment for a time sufficient to induce a change in arterial volume of the limb segment upon release of the cuff inflation pressure;

wherein the processor controls the cuff to apply a series of external pressures on the limb segment at the mean arterial pressure of the limb segment and controls the sensor to detect non-extremity partial volume pulse waves of the limb segment during the baseline and after stimulation.

36. A diagnostic system for assessing changes in arterial volume of a limb segment of a mammal, comprising:

wherein the processor controls the cuff to apply external pressure to the limb segment at a pressure level that causes blood flow through the artery to generate the volume pulse waves in response to the applied external pressure during the baseline period and after the stimulation.

37. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment and gradually changes the external pressure between a near systolic pressure and a near diastolic pressure, and wherein the processor controls the sensor to detect a volume pulse wave at which the external pressure is between the systolic pressure and the diastolic pressure.

38. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment at a pressure near systolic pressure and gradually decrease the external pressure to near diastolic pressure.

39. The diagnostic system of claim 36, wherein the processor controls the cuff to apply the external pressure to the limb segment at a pressure near diastolic blood pressure and to gradually increase the external pressure to near systolic blood pressure.

40. The diagnostic system of claim 36, wherein the processor controls the cuff to cycle the external pressure applied to the limb segment between a high pressure and a low pressure,

wherein the processor determines an amplitude of a component pulse wave of the volume pulse wave measured when the external pressure is at the high pressure.

41. The diagnostic system of claim 40, wherein the high pressure is near mean arterial pressure and the low pressure is below venous pressure.

42. The diagnostic system of claim 40, wherein the high pressure is below diastolic pressure and the low pressure is below venous pressure.

43. A diagnostic system for assessing changes in arterial volume of a limb segment of a mammal, comprising:

a sensor for detecting a non-extremity partial volume pulse wave of a limb segment in a basal period and detecting the non-extremity partial volume pulse wave of the limb segment during a period of arterial volume change after stimulation; and

wherein the pulse component is an early systolic component; and

the processor calculates a fourth order derivative of the measured volume pulse wave, determines a time point at which the fourth order derivative crosses a zero line for the third time, determines a pressure value on the measured volume pulse wave at the time point, determines a pressure value at a starting point of the volume pulse wave, and evaluates the amplitude of an early contraction component wave in the volume pulse wave as a difference between the pressure values to determine the amplitude of the early contraction component wave in the volume pulse wave.

44. The diagnostic system of claim 43, wherein the processor determines a minimum value of the pulse wave corresponding to a single diastole of the mammal to determine the pressure value at the beginning of the volume pulse wave.