Patent Description:
In many cases, increased blood vessel stiffness, especially arterial stiffness, occurs because of biological aging and arteriosclerosis. Increased arterial stiffness is associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, which are two leading causes of death in the developed world. An increase in arterial stiffness also increases the load of the heart, since the heart needs to perform more work to maintain a required stroke volume. Over time, this increased workload causes left ventricular hypertrophy and left ventricular remodelling, which can lead to a heart failure. The increased workload may also be associated with a higher heart rate, a proportionately longer duration of systole, and a reduction of duration of diastole. This decreases the amount of time available for perfusion of cardiac tissue, which mainly occurs during diastole. Thus, a hypertrophic heart, which has a greater oxygen demand, may have a compromised supply of oxygen and nutrients. Increased arterial stiffness may also affect the time at which pulse wave reflections return to the heart. When a pulse wave travels through the circulation it undergoes reflection at sites where the transmission properties of the arterial tree change, i.e. at sites of flow impedance mismatch. These reflected waves propagate backwards towards the heart. The speed of propagation is increased in stiffer arteries and consequently reflected waves will arrive at the heart earlier in systole. This increases the load of the heart in systole.

Due to the reasons of the kind mentioned above, several techniques have been developed to estimate the stiffness of blood vessels. A commonly used method for measuring the arterial stiffness is based on pulse wave velocity "PWV", i.e. the speed at which an arterial pulse propagates along an artery. The PWV is indicative of the arterial stiffness because higher arterial stiffness corresponds to higher PWV in accordance with the Bramwell-Hill equation. The PWV can be calculated by measuring a pulse transit time and a distance travelled between two selected sites. A more detailed description of the method based on the PWV can be found e.g. in the publication <NPL>.

Publication <NPL> describes a multi-wavelength photoplethysmography "MWPPG" device for studying the skin microvasculature. The device utilizes the fact that the penetration depth of light into the skin is depended on the light wavelength. Thus, the device allows to study blood vessels at different depths.

Publication <CIT> describes a method for cuff-less blood pressure measurement. The method comprises recording a physiological signal and multi-wavelength photoplethysmography "PPG" signals from a predetermined body part, deriving the depth-specific PPG signal reflecting the arterial blood volume with the physiological signal as a reference, calculating the pulse transit time "PTT" from the physiological signal and the derived arterial blood PPG signal, and calculating the blood pressure from the calculated PTT and blood pressure relationship.

Publication <CIT> describes a device for non-invasive capillary blood pressure measurement. The device comprises a front end in contact with a body to compress and decompress capillaries in tissue, a pressure control module for regulating contact pressure between the front end and the tissue, a pressure transducer coupled to the front end for measuring the contact pressure, a capillary sensing module for detecting capillary pulsations under the contact pressure modulation, and a computing system for running an algorithm to determine capillary pressure based on the capillary pulsations and the contact pressure modulation.

Publication <NPL> describes a photoplethysmography technique to derive arterial stiffness so that the finger arterial elasticity index "FEI" is defined as a parameter n which denotes the curvilinearity of a descriptive exponential model of pressure P - volume Va relationship: Va = a - b e-nP, where a and b are parameters of the descriptive exponential model.

Publication <CIT> describes an apparatus for measuring functionality of an arterial system of an individual. The apparatus comprises a photoplethysmography sensor for emitting, to the arterial system, electromagnetic radiation having a wavelength in the range from <NUM> to <NUM> and for receiving a part of the electromagnetic radiation reflected off the arterial system. The apparatus further comprises a pressure instrument for managing mechanical pressure applied on the arterial system when the photoplethysmography sensor emits and receives the electromagnetic radiation to and from the arterial system. The effect of the mechanical pressure on the envelope of the reflected electromagnetic radiation can be used for determining diastolic blood pressure of arteries or for determining whether there is normal endothelial function.

There is, however, still a need for techniques for measuring data indicative of the stiffness of blood vessels quickly and cost effectively.

The following presents a simplified summary in order to provide a basic understanding of some aspects of various invention embodiments.

In accordance with the invention, there is provided a new apparatus for measuring compliance of blood vessels. The compliance is indicative of the stiffness of the blood vessels so that a lower compliance corresponds to a greater stiffness. An apparatus according to the invention comprises:.

The control system is configured to find, from the measurement signal, a portion whose envelope, i.e. a curve outlining extremes of the measurement signal, has exponential change, i.e. exponential growth ~eαt or exponential decrease ~e-αt, with respect to time and to produce an estimate for a coefficient α of time related to the exponential change, the exponential change being exponential increase when the mechanical pressure is linearly decreased with respect to time, and the exponential change being exponential decrease when the mechanical pressure is linearly increased with respect to time. The coefficient of time is indicative of the compliance of the blood vessels and thereby indicative of the stiffness of the blood vessels, too.

The above-mentioned pressure instrument can be for example a device for directing mechanical pressure to a fingertip or a toe, or a device comprising a cuff and a pump system for controlling gas pressure inside the cuff to direct mechanical pressure to an arm. Thus, use of the apparatus according to the invention does not need e.g. measurements from different sites of a body unlike a method based on the pulse wave velocity "PWV".

The photoplethysmography "PPG" sensor can be configured to emit electromagnetic radiation having wavelength for example in the range from <NUM> to <NUM>, i.e. red or infrared light, in order to measure compliance of arteries located in the hypodermis, and/or electromagnetic radiation having wavelength for example in the range from <NUM> to <NUM>, i.e. yellow light, in order to measure compliance of blood vessels located in an upper portion of the hypodermis, and/or electromagnetic radiation having wavelength for example in the range from <NUM> to <NUM>, i.e. green light, in order to measure compliance of arterioles located in the dermis, and/or electromagnetic radiation having wavelength for example in the range from <NUM> to <NUM>, i.e. blue light, in order to measure compliance of capillaries located in an upper portion of the dermis.

It is to be noted that the above-mentioned wavelengths are examples only and a measurement of compliance of blood vessels can be carried out with many different suitable wavelengths. A radiation emitter of a PPG sensor may comprise for example one of more light emitting diodes "LED" and/or laser sources. Furthermore, a continuum of compliance values can be measured using for example a radiation emitter having an adjustable wavelength.

In an exemplifying case where different waveforms are used, it is possible to measure the compliances of different blood vessels and thereafter compute a ratio of at least one pair of the measured compliances corresponding to different wavelengths, where each ratio expresses a stiffness mismatch between smaller and greater blood vessels wherein a shorter wavelength relates to the smaller blood vessels and a longer wavelength relates to the greater blood vessels.

In accordance with the invention, there is provided also a new method for measuring compliance of blood vessels. A method according to the invention comprises:.

In accordance with the invention, there is provided also a new computer program for measuring compliance of blood vessels. A computer program according to the invention comprises computer executable instructions for controlling a programmable processing system to:.

In accordance with the invention, there is provided also a new computer program product. A computer program product according to the invention comprises a nonvolatile computer readable medium, e.g. a compact disc "CD", encoded with a computer program according to the invention.

Exemplifying and non-limiting embodiments are described in accompanied dependent claims.

Various exemplifying and non-limiting embodiments both as to constructions and to methods of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific exemplifying embodiments when read in conjunction with the accompanying drawings.

The features recited in the accompanied dependent claims are mutually freely combinable unless otherwise explicitly stated.

Exemplifying and non-limiting embodiments and their advantages are explained in greater detail below with reference to the accompanying drawings, in which:.

The specific examples provided in the description below should not be construed as limiting the scope and/or the applicability of the appended claims. Lists and groups of examples provided in the description are not exhaustive unless otherwise explicitly stated.

<FIG> shows a schematic illustration of an apparatus according to an exemplifying and non-limiting embodiment for measuring compliance of blood vessels. The apparatus comprises a photoplethysmography "PPG" sensor <NUM> for emitting, to a fingertip <NUM> of an individual, electromagnetic radiation and for receiving a part of the electromagnetic radiation reflected off the blood vessels of the fingertip <NUM>. The PPG sensor <NUM> comprises a radiation emitter <NUM> and a photodetector <NUM>. The radiation emitter <NUM> may comprises e.g. one or more light emitting diodes "LED" and the photodetector <NUM> may comprise e.g. one or more photodiodes or phototransistors. <FIG> shows also a magnified, schematic section view <NUM> of the fingertip. The section plane is parallel with the yz-plane of a coordinate system <NUM>.

In the exemplifying apparatus illustrated in <FIG>, the PPG sensor <NUM> is configured to emit the electromagnetic radiation so that the electromagnetic radiation contains radiation components with five different wavelengths. In the section view <NUM>, the radiation components are depicted with polyline arrows <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>. The first radiation component <NUM> can be for example infrared radiation having a wavelength on the range from <NUM> to <NUM>, the second radiation component <NUM> can be for example red radiation having a wavelength on the range from <NUM> to <NUM>, the third radiation component <NUM> can be for example yellow radiation having a wavelength on the range from <NUM> to <NUM>, the fourth radiation component <NUM> can be for example green radiation having a wavelength on the range from <NUM> to <NUM>, and the fifth radiation component <NUM> can be for example blue radiation having a wavelength on the range from <NUM> to <NUM>. For another example, the first radiation component <NUM> can be infrared radiation having a wavelength on the range from <NUM> to <NUM>, the second radiation component <NUM> can be red radiation having a wavelength on the range from <NUM> to <NUM>, the third radiation component <NUM> can be yellow radiation having a wavelength on the range from <NUM> to <NUM>, the fourth radiation component <NUM> can be green radiation having a wavelength on the range from <NUM> to <NUM>, and the fifth radiation component <NUM> can be blue radiation having a wavelength on the range from <NUM> to <NUM>.

As illustrated in the section view <NUM>, the red and infrared radiation components <NUM> and <NUM> reach arteries <NUM> located in the hypodermis <NUM>, the yellow radiation component <NUM> reach blood vessels located in a portion of the hypodermis <NUM> adjacent to the dermis <NUM>, the green radiation component <NUM> reach arterioles <NUM> located in the dermis <NUM>, and the blue radiation component <NUM> reach capillaries <NUM> located in a portion of the dermis <NUM> adjacent to the epidermis <NUM>. Therefore, shorter wavelengths relate to smaller blood vessels, i.e. blood vessels nearer to a skin surface, than longer wavelengths. In the exemplifying apparatus illustrated in <FIG>, the photodetector <NUM> of the PPG sensor <NUM> is configured produce a measurement signal that comprises wavelength-specific component signals indicative of received wavelengths reflected off the blood vessels. <FIG> shows graphs illustrating exemplifying wavelength-specific component signals <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> of an exemplifying measurement signal <NUM>. The wavelength-specific component signal <NUM> corresponds to infrared radiation, the wavelength-specific component signal <NUM> corresponds to red radiation, the wavelength-specific component signal <NUM> corresponds to yellow radiation, the wavelength-specific component signal <NUM> corresponds to green radiation, and the wavelength-specific component signal <NUM> corresponds to blue radiation. The photodetector <NUM> may comprise for example many photodiodes or phototransistors that are sensitive to different wavelengths, or the photodetector <NUM> may comprise filters to implement wavelength separation.

The apparatus comprises a pressure instrument <NUM> configured to produce mechanical pressure P applied on the blood vessels. The apparatus comprises a control system <NUM> configured to control the pressure instrument <NUM> to change, i.e. to decrease or increase, the mechanical pressure linearly with respect to time t during emission of the electromagnetic radiation to the blood vessels and reception of the reflected electromagnetic radiation from the blood vessels. <FIG> shows a line <NUM> illustrating the time dependence of the mechanical pressure in the exemplifying case in which the mechanical pressure has been linearly decreased and the above-mentioned wavelength-specific component signals <NUM>-<NUM> have been measured. The pressure values P1, P2, and P3 can be e.g. <NUM> mmHg, <NUM> mmHg, and <NUM> mmHg, respectively.

In the exemplifying apparatus illustrated in <FIG>, the pressure instrument <NUM> comprises a pressure sensor <NUM> for measuring the mechanical pressure P directed by the fingertip <NUM> to the pressure sensor <NUM> and pressing means for controllably pressing the fingertip <NUM> against the PPG sensor <NUM> and the pressure sensor <NUM>. In this exemplifying apparatus, the pressing means comprise a pressing element <NUM> and a force generator <NUM> for directing force to the pressing element <NUM>. The force generator <NUM> may comprise for example an electric stepper motor and a threaded rod or some other suitable elements for generating force.

The control system <NUM> is configured to find, from each wavelength-specific component of the measurement signal, a portion whose envelope has exponential change, i.e. exponential growth or exponential decrease, with respect to time and to produce an estimate for a coefficient of time related to the exponential change. The coefficient of time is indicative of the compliance of the blood vessels and thereby also the stiffness of the blood vessels.

As mentioned above, in the exemplifying case illustrated in <FIG>, the mechanical pressure is linearly decreased and thus each of the wavelength-specific component signals <NUM>-<NUM> has a portion whose envelope has exponential growth. <FIG> shows a magnification of a part of the wavelength-specific component signal <NUM>. In <FIG>, the envelopes of the wavelength-specific component signals <NUM>-<NUM> are depicted with thick lines. The exponential growth ~eαYt on a part of the envelope of the wavelength-specific component signal <NUM> is depicted with a dashed line. In this case, the coefficient of time related to the exponential growth is αY. Thus, the coefficient of time αY is indicative of the compliance of the blood vessels and thereby also the stiffness of the blood vessels from which yellow light is reflected off.

There are many ways to find the portion whose envelope has the exponential change and to produce the estimate for the coefficient of time related to the exponential change. For example, curve fitting based on e.g. the least-mean-square "LMS" method can be used. Thus, apparatuses according to embodiments of the invention are not limited to any specific ways to find the portion whose envelope has the exponential change and to produce the estimate for the coefficient of time related to the exponential change.

In an apparatus according to an exemplifying and non-limiting embodiment, the control system <NUM> is configured to convert the wavelength-specific components <NUM>-<NUM> of the measurement signal to a logarithmic scale. <FIG> shows graphs illustrating the converted wavelength-specific component signals <NUM>', <NUM>', <NUM>', <NUM>', and <NUM>' which corresponds to the wavelength-specific component signals <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> shown in <FIG>, respectively. Due to the logarithmic conversion, the exponential growth is converted into linear growth that is depicted with lines <NUM>", <NUM>", <NUM>", <NUM>", and <NUM>" shown in <FIG>. Concerning the linear growth, the control system <NUM> is configured to produce an estimate for a slope of the envelope of each converted wavelength-specific component signal. The slope is the coefficient of time related to the exponential growth. In the exemplifying case shown in <FIG> and <FIG>, the slope i.e. the coefficient of time related to the infrared light is αIR, the coefficient of time related to the red light is αR, the coefficient of time related to the yellow light is αY, the coefficient of time related to the green light is αG, and the coefficient of time related to the blue light is αB. Thus, for example, αR is the indicative of compliance of arteries and thereby also the stiffness of the arteries, αG is indicative of compliance of arterioles and thereby also the stiffness of the arterioles, and as is indicative of compliance of capillaries and thereby also the stiffness of the capillaries.

In an apparatus according to an exemplifying and non-limiting embodiment, the control system <NUM> is configured to compute a ratio of at least one pair of the coefficients of time corresponding to different wavelengths. Each ratio expresses a stiffness mismatch between blood vessels having different sizes where a shorter wavelength relates to smaller blood vessels and a longer wavelength relates to larger blood vessels. For example, the ratio αR/αG is indicative of the stiffness mismatch between arteries and arterioles.

In the exemplifying apparatus illustrated in <FIG>, the PPG sensor <NUM> is configured to emit and receive different wavelengths simultaneously. It is however also possible that the control system of an apparatus according to an exemplifying and non-limiting embodiment is configured to control the PPG sensor to variate the wavelength of the electromagnetic radiation, and to produce the coefficients of time for different wavelengths successively.

<FIG> shows a schematic illustration of an apparatus according to an exemplifying and non-limiting embodiment for measuring compliance of blood vessels. The apparatus comprises a photoplethysmography "PPG" sensor <NUM> for emitting electromagnetic radiation and for receiving a part of the electromagnetic radiation reflected off blood vessels of an arm. The PPG sensor <NUM> is configured to produce a measurement signal indicative of the received part of the electromagnetic radiation. The apparatus comprises a pressure instrument <NUM> configured to produce mechanical pressure applied on the blood vessels. The apparatus comprises a control system <NUM> configured to control the pressure instrument <NUM> to change the mechanical pressure linearly with respect to time during emission of the electromagnetic radiation to the blood vessels and reception of the reflected electromagnetic radiation from the blood vessels. The control system <NUM> is configured to find, from the above-mentioned measurement signal, a portion whose envelope has exponential change, ~eαt or ~e-αt, with respect to time and to produce an estimate for a coefficient α of time related to the exponential change. The coefficient α of time is indicative of the compliance of the blood vessels and thereby indicative of the stiffness of the blood vessels.

In the exemplifying apparatus illustrated in <FIG>, the pressure instrument <NUM> comprises a cuff and a pump system <NUM> configured to control gas pressure inside the cuff to direct the mechanical pressure to the arm and to change the mechanical pressure when the PPG sensor <NUM> emits and receives the electromagnetic radiation to and from the arm. The PPG sensor is located on an inner surface of the cuff.

Each of the control systems <NUM> and <NUM> shown in <FIG> and <FIG> can be implemented for example with one or more processor circuits, each of which can be a programmable processor circuit provided with appropriate software, a dedicated hardware processor such as for example an application specific integrated circuit "ASIC", or a configurable hardware processor such as for example a field programmable gate array "FPGA". Each of the control systems <NUM> and <NUM> may further comprise memory implemented for example with one or more memory circuits each of which can be e.g. a random-access memory "RAM" device.

<FIG> shows a flowchart of a method according to an exemplifying and non-limiting embodiment for measuring compliance of blood vessels. The method comprises the following actions:.

In a method according to an exemplifying and non-limiting embodiment, the electromagnetic radiation has wavelengths selected from at least two of the following ranges: from <NUM> to <NUM>, from <NUM> to <NUM>, from <NUM> to <NUM>, and from <NUM> to <NUM>.

In a method according to an exemplifying and non-limiting embodiment, the electromagnetic radiation has different wavelengths and the measurement signal comprises wavelength-specific component signals being indicative of received wavelengths reflected off the blood vessels, and the coefficient of time is produced for each of the wavelength-specific component signals corresponding to the different wavelengths where a shorter one of the wavelengths relates to smaller ones of the blood vessels than a longer one of the wavelengths.

In a method according to an exemplifying and non-limiting embodiment, the wavelength of the electromagnetic radiation is varied, and the coefficient of time is produced for each value of the wavelength where a shorter wavelength relates to smaller ones of the blood vessels than a longer wavelength.

A method according to an exemplifying and non-limiting embodiment comprises computing a ratio of at least one pair of the coefficients of time corresponding to different wavelengths, each ratio expressing a stiffness mismatch between ones of the blood vessels having different sizes where a shorter wavelength relates to smaller ones of the blood vessels than a longer wavelength.

A method according to an exemplifying and non-limiting embodiment comprises converting the measurement signal to a logarithmic scale, finding from the converted measurement signal a portion whose envelope has linear change with respect to time, and producing an estimate for a slope of the envelope of the converted measurement signal related to the linear change. The slope of the linear change is the coefficient of time related to the exponential change.

In a method according to an exemplifying and non-limiting embodiment, the mechanical pressure is directed to a fingertip or a toe of an individual.

In a method according to an exemplifying and non-limiting embodiment, the mechanical pressure is directed to an arm of an individual with a cuff and a pump system configured to control gas pressure inside the cuff. In this exemplifying case, the photoplethysmography sensor is located on an inner surface of the cuff.

A computer program according to an exemplifying and non-limiting embodiment comprises computer executable instructions for controlling a programmable processing system to carry out actions related to a method according to any of the above-described exemplifying and non-limiting embodiments.

A computer program according to an exemplifying and non-limiting embodiment comprises software modules for measuring compliance of blood vessels. The software modules comprise computer executable instructions for controlling a programmable processing system to:.

The software modules can be for example subroutines or functions implemented with programming tools suitable for the programmable processing equipment.

A computer program product according to an exemplifying and non-limiting embodiment comprises a computer readable medium, e.g. a compact disc "CD", encoded with a computer program according to an exemplifying embodiment.

A signal according to an exemplifying and non-limiting embodiment is encoded to carry information defining a computer program according to an exemplifying embodiment.

A computer program according to an exemplifying and non-limiting embodiment may constitute e.g. a part of a software of a mobile device, e.g. a smart phone or a wearable device.

Claim 1:
apparatus for measuring compliance of blood vessels, the apparatus comprising:
- a photoplethysmography sensor (<NUM>, <NUM>) configured to emit electromagnetic radiation to the blood vessels, to receive a part of the electromagnetic radiation reflected off the blood vessels, and to produce a measurement signal (<NUM>) indicative of the received part of the electromagnetic radiation,
- a pressure instrument (<NUM>, <NUM>) configured to produce mechanical pressure applied on the blood vessels, and
- a control system (<NUM>, <NUM>) configured to control the pressure instrument to change the mechanical pressure linearly with respect to time (t) during emission of the electromagnetic radiation to the blood vessels and reception of the part of the electromagnetic radiation reflected off the blood vessels,
characterized in that the control system is configured to find, from the measurement signal, a portion whose envelope has exponential change (~eαt or ~e-αt) with respect to time and to produce an estimate for a coefficient (α) of time related to the exponential change, the coefficient of time being indicative of the compliance of the blood vessels, the exponential change being exponential increase when the mechanical pressure is linearly decreased with respect to time, and the exponential change being exponential decrease when the mechanical pressure is linearly increased with respect to time.