Measurement of pulse wave velocity

The invention relates to an apparatus to measure pulse wave velocity, PWV, along a pathway in the cardiovascular system of a subject, with a first sensor for placement at the surface of the subject, to detect a first signal originating from a first position on a pathway in the cardiovascular system of the subject, the first signal detected at a first time, the first sensor coupled to a processor, and a second sensor for placement at the surface of the subject, to detect a second signal originating from a second position on the pathway in the cardiovascular system of the subject, the second signal detected at a second time, the second sensor coupled to the processor, the first and second positions situated a distance apart along the pathway, the processor arranged to calculate the PWV from the values of the first position, the second position, the first time and the second time.

It is known that the pulse wave velocity, PWV, of the arterial pulse of an individual is dependent on the health of the individual and therefore can be used to diagnose arterial pathology.

Noninvasive Assessment of Vascular Mechanics in Mice, by Craig J. Hartley et al, Proceedings of the Second Joint EMBS/BMES Conference, October 23-26, 2002 discloses the measurement of velocity pulse arrival times utilizing doppler ultrasound for determining pulse-wave velocity. Simultaneous measurements of velocity are made at two sites separated by a known distance. The two acquired signals are displayed and the difference in pulse arrival times extracted to calculate pulse wave velocity, PWV.

WO0176473 discloses the measurement of flow along an anatomical flow conduit using mechanical or pressure sensors placed along the external surface of the body at some known distance apart. The sensors are attached to a rigid support means designed to wrap around a limb, by which the sensors can be brought into reliable contact with the body surface. The sensors detect pressure or mechanical signals palpable at the body surface. An option is included to time the detection of the second signal relative to an electrical start signal, for example an ECG measurement. However, the support means is quite restrictive and difficult to place. Further, by measuring pressure or mechanical signals at the surface of the body the apparatus does not measure the time difference between arterial pulses directly, but rather measures a secondary signal from which PWV is then calculated.

Pulse Wave Velocity for Cardiovascular Characterization, by David S. Charles and Martin D. Fox, IEEE, discloses the measurement of PWV in the human body by placing doppler ultrasound probes a known distance along an arterial pathway, detecting doppler signals at each probe and using the time difference between the detection of each signal to calculate PWV. An option is provided to use ECG instead of the first doppler ultrasound probe. In this latter case the ECG provides a start signal from which to time the arrival at the second probe of the initial pulse generated at the heart. As described in the text, the doppler ultrasound probe can only provide the required signal if the probe is correctly and carefully angled onto the surface of the skin. This requires skilled and experienced personnel and therefore limits the use of this measurement apparatus to situations in which such skilled and experienced staff are available. Further, use of doppler ultrasound requires acoustic gel between the probe and the skin in order to provide a good acoustical match. The gel is sticky and wet to the touch and transfers readily upon contact, making it difficult to clean up. Also patients frequently dislike the sensation of being in contact with the gel.

It is an object of the invention to provide an alternative apparatus to measure PWV directly but which does not require the use of acoustic gel.

This is achieved according to the invention whereby at least one sensor is a transducer arranged to emit electromagnetic signals at a certain frequency and detect doppler shifted reflected electromagnetic signals representative of a pulsatile motion occurring at the respective position in the cardiovascular system. Electromagnetic signals reflect from any boundary between materials with differing dielectric constants. The feature of using a transducer arranged to emit electromagnetic signals and detect doppler shifted return signals allows the emission into the body of a signal which can be reflected from any boundary between two tissue types with differing dielectric constants and which can encode any movement of those boundaries which has a component along the direction of propagation of the electromagnetic signals. Therefore these signals can be used to detect the passing of a pulse along a cardiovascular route in the body and can therefore be used to measure the pulse transit time. As is known by the skilled person, the measurement of pulse transit time can be coupled to the measured or calculated distance between sensors that measure the passing pulse and can be combined to calculate the pulse wave velocity, or PWV. As is known, the pulse wave velocity can be used as an indicator of the physiological status of an artery and of the patient's hemodynamic status.

The heart, as the organ which pumps blood around the body, is subdivided into 4 chambers, 2 atria which receive blood entering the heart and 2 larger ventricles which pump blood out of the heart. Deoxygenated blood returning from the body enters the right atrium and is pumped out to the lungs through the right ventricle. Oxygenated blood returning from the lungs enters the left atrium of the heart and is pumped via the left ventricle, the largest chamber in the heart, into the rest of the body via the vascular system. The entire system of heart and blood vessels is known as the cardiovascular system. The blood vessels are differentiated into the arteries, capillaries and veins. Arteries are muscular and essentially tubular blood vessels capable of withstanding the pulsatile flow of blood ejected from the heart. The pumping action of the heart causes blood to enter the arterial system in a series of strong bursts and the arterial walls are evolved to withstand the cyclical distension and contraction caused by the passing of each bolus of blood as it is pumped out. The arterial system distributes blood away from the heart and into the capillary network where oxygen carried by the red blood cells transfers into the surrounding tissue and waste products transfer into the blood cells. From there the blood, now essentially deoxygenated and containing waste products, enters the venous system, or system of veins, where it is transferred back up to the heart. The passing of each bolus of blood as it is pumped out of the heart and along the arterial system causes a pulsatile distension of the arterial walls to travel along the artery. It is this passing pulsatile movement which is detected by the transducer and which allows the transducer to be used for the calculation of PWV.

The passing pulse detected by the transducer occurs when an arterial pulse is transmitted along an arterial pathway. The passing of the pulse of blood and the associated pulsatile distension of the surrounding arterial tissue causes doppler shifting of the reflected radar and allows a signal to be detected which indicates that a pulse has passed below the stationary transducer. The detection of this signal allows the passing of the pulse to be timed and thereby allows the measurement of the transit time of the pulse along a distance along the arterial route, or pathway.

The invention does not require an air tight or other coupling contact between the surface of the skin and the surface of the transducer because electromagnetic signals are transmissable through air. Therefore use of the apparatus does not require the use of any gel. Therefore specifically it can be seen that the invention achieves the object of the calculation of PWV without the use of acoustic gel.

It has the further advantage that it does not require a direct placement against bare skin but can be placed against clothing. The invention has the further advantage that it does not require a rigid construction to attach the doppler transducer to the skin surface but can merely be placed manually and held.

Several advantageous embodiments are now described. In the first, two transducers are utilized, placed a distance apart along an arterial pathway. Particularly advantageous sites for the placement of the transducers is along the inner, or medial, surface of the arm. Signals from both transducers can be detected and processed to identify the passing of an arterial pulse below the transducers and further to identify the minimum time between pulses and therefore to identify the time difference between the passing of the pulse below the upper transducer and the arrival of the pulse at the lower transducer. This time difference can be used along with knowledge of the distance at which the transducers are placed apart to calculate the PWV, as is known in the art.

In a second embodiment an ECG arrangement is used to identify the production of an arterial pulse and the transducer is used to identify the passing of the pulse at some point further along the arterial tree. The time difference between the measurement of the ECG signal and the detection of the signal from the transducer can be calculated, and as is known in the art, used along with knowledge of the position of the doppler transducer to calculate PWV.

In a third embodiment the transducer is used for the first sensor and the second sensor is a photoplethysmography sensor. Further possibilities include using an audio-microphone, or some other sensor receptive to sound, positioned on the thorax to pick up heart sounds.

The apparatus of the invention can be used with a transducer arranged to produce electromagnetic signals of frequency in a range of between 400 MHz and 5 GHz. This range produces reflected signals from the passing pulsatile motion. However, the apparatus works in a particularly advantageous manner when the frequency is in a range of between 800MHz and 4 GHz.

Transducers for the detection of doppler shifted signals are commercially available, often for the purposes of far field detection of movement, for example Radar measurements of traffic speed. It is now found, according to the invention that such transducers can also be used for near field measurements and are surprisingly suitable for detecting the passing of pulses in the cardiovascular system.

Generally in such doppler transducers, as is known in the art, an antenna emits an electromagnetic wave which, when it is reflected from the surfaces of an object moving with a component of velocity non-transverse to the impinging electromagnetic wave, produces a shift in the frequency of the electromagnetic wave reflected back to the antenna. This shift in frequency is called the doppler shift. This doppler shifted reflected wave is then detected by an antenna in the transducer, which may or may not be the emitting transducer. The relative speed of movement of the reflecting object is encoded in the frequency shift of the detected reflected wave and this value can be extracted using known techniques.

The transducer advantageously described contains a 2.45 GHz oscillator operating in continuous mode. It is known that electromagnetic radiation is strongly absorbed in human tissue at around the frequencies of 2 to 10 GHz, but it is found, according to a highly advantageous embodiment of the invention, that the radiation produced from an antenna operating at 2.45 GHz, although absorbed and scattered to some extent by layers of tissue, produces a detectable signal.

A particularly advantageous embodiment utilizes a commercially available KMY 24 unit made by Micro Systems Engineering GmbH. It contains a 2.45 GHz oscillator and receiver in the same housing and works in continuous wave mode. The module comprises a four layered epoxy-multilayer-board with SMD-components and with triplate- filter-structures to minimize the emission of harmonics. The dimensions of the beam are, amongst other things, dependent on the dimensions of the antenna and in this case the unit contains an optimized patch antenna with minimized dimensions and a width of 3.5 cm, producing a beam with a near field radius of 2 cm. The receiver is sensitive enough to process signals that are reflected by the passing of a pulse through the emitted electromagnetic beam.

The technical steps to be performed in the processing of the recorded data to provide an output of PWV can be undertaken by a person skilled in the art using known data processing techniques. The invention also relates to a method of calculating pulse wave velocity,

PWV, along a pathway in the cardiovascular system of a subject, wherein a first time is calculated at which a first signal from a first pulse is detected by a first sensor, the first pulse originating from a first position on a pathway in the cardiovascular system of the subject, a second time is calculated at which a second signal from a second pulse is detected by a second sensor, the second pulse originating from a second position on the pathway in the cardiovascular system of the subject, the first and second positions separated by a distance along the pathway, and PWV is calculated from the values of the first position, the second position, the first time and the second time, and in which at least one sensor is a transducer arranged to emit electromagnetic signals at a certain frequency and detect doppler shifted reflected electromagnetic signals representative of a pulsatile motion occurring at the respective position in the cardiovascular system. This method has the advantage that it can be used with the apparatus to perform the invention.

The invention is further elucidated and embodiments described using the following figures.

Fig. 1 shows a high level block diagram of the features of a transducer used advantageously in the apparatus of the invention. Fig. 2 shows items of an embodiment of the apparatus of the invention applied to a human arm.

Fig. 3 shows output signals from the apparatus of Fig. 2. Fig. 4 shows a further embodiment of the apparatus of the invention applied to a subject. Fig. 5 shows a typical ECG trace which is used in the second embodiment of the invention.

Fig. 6 shows output signals from the transducer and the ECG apparatus of the second embodiment, shown in Fig. 4, when the transducer is applied to the upper arm.

Fig. 7 shows output signals from the transducer and the ECG apparatus of the second embodiment, shown in Fig. 4, when the transducer is applied to the wrist.

Figure 1 shows a high level block diagram of the features of a transducer used advantageously in the apparatus of the invention. Processing electronics 101 instruct a duplexer 102 to send electromagnetic signals of frequency f_s which are emitted by an antenna 103. Reflected electromagnetic signals doppler shifted to frequency f_r are received by the antenna 103, passed back to the duplexer 102 and sent to processing electronics 104 which receives the signal and calculates fo the shift in frequency between the emitted and received electromagnetic signals, as is known in the art. Although a single antenna 103 is shown here, separate antennas may be used for sending and receiving the electromagnetic signals. The shift in frequency fo is communicated to a processor 105 which performs synchronization and analysis.

Figure 2 shows the apparatus of the first embodiment of the invention. In this embodiment two transducers are applied to the arm of a subject and measure the times at which a signal is returned from the pulsatile motion along the arm caused by blood flow. The first transducer 201 is positioned over the brachial artery of the arm. The second transducer 202 is adventitiously positioned over the radial artery which provides a clear signal. The second transducer 203 can also be positioned so that the beam of electromagnetic signals is doppler shifted from pulsatile flow along the ulna artery. The skilled person will understand that the exact positioning of the two transducers is chosen to measure PWV along the arterial pathway of interest and transducers must be adjusted to provide the best signal.

It is found in practice that the transducer must be held motionless for a few seconds against the skin or clothing to allow movement artifacts to decrease and to allow whatever signal is received to be detected. It is apparent if the transducer has been misplaced to the extent that no pulsatile flow occurs in the beam of the electromagnetic signals, for in that case no signal is received.

Figure 3 shows a plot of the doppler shifted signals received from the apparatus of the first embodiment, as shown in Figure 2, and shows two traces 301 and 302, each from one of the transducers, plotted against time. The signal which occurs first temporally 301, is from the transducer of the first embodiment which is placed in the upper position on the arm. The signals are synchronously recorded. The time difference of a pulse passing each transducer is clearly visible and in this case is 50 ms. Standard algorithms, known by the skilled person, are used to automatically extract the peak-to-peak time and these are used along with the known distance between the sensors to calculate PWV, as is known in the art. It is possible to place the transducers at other parts of the body, for example along the pathways taken by arteries in the leg. If positioned correctly, it is possible to place one or both transducers over the aorta and measure the PWV of an arterial pulse along the aorta or along a pathway from the aorta to, say, the upper brachial artery. Typically, the PWV, which can be as high as 12 m/s, is higher than the flow velocity of blood, which is less than 1 m/s.

Figure 4 shows a further embodiment of the apparatus of the invention applied to a subject. In this second embodiment the second sensor is the transducer 401 and an arrangement of ECG electrodes 402, 403, 404 and processing device 405 is used to acquire the first signal. In this case the signal is the ECG signal from the heart itself. As is known in the art, measurements from electrocardiography, ECG, show that the heart pumps in a cyclical fashion and allows the identification of certain phases in the hearts electrical sequence. Figure 5 shows a typical output trace from an ECG measurement. The characteristic spikes shown in a typical trace are labeled P, Q, R, S and T. It is known that the P spike, or wave, is representative of the depolarization, or excitation, of the atria. The QRS spikes, known commonly as the QRS-complex, are representative of the excitation of the ventricles. The QRS-complex masks any signal from the repolarisation of the atria. The T spike, or T wave, is representative of the repolarisation of the ventricles.

Figure 6 shows the output signals from the transducer 601 and the ECG apparatus 602 of the second embodiment when the transducer is applied to the upper arm and therefore detects a return signal from movement of the brachial artery. Again, standard algorithms, as is known in the art, can be used to extract the time differences between the R peak and characteristic points of the doppler radar signal, as shown, and these are used, as is known in the art, to calculate PWV.

Figure 7 shows a similar output, in this case from the transducer 701 and the ECG apparatus 702 of the second embodiment when the transducer is applied to the wrist and therefore detects a return signal from movement of the radial artery. Again, standard algorithms, as is known in the art, can be used to extract the time differences between the R peak and characteristic points of the doppler radar signal, as shown, and these are used, as is known in the art, to calculate PWV.

In a third embodiment a photoplethysmography sensor is used as the second sensor. This embodiment is particularly useful during surgery when a photoplethysmography sensor is placed on the tip of a finger to monitor blood oxygenation during anesthesia. In this embodiment, the doppler transducer can be applied anywhere along the arm where access is possible under the constraints of the surgical procedure and where a suitable signal can be found. The photoplethysmography sensor, designed to detect small changes in blood volume, is used to detect the arrival of pulsatile blood flow in the tip of the finger. The PWV calculated using this embodiment can be used to provide information about the physiological status of the arteries of the upper arm during surgery.

In a further embodiment a microphone is used as the first sensor. This is particularly useful to get rid of the typically unknown pre-ejection period compared with the embodiment detecting the ECG via a first sensor, because the ECG represents the electrical excitation of the heart and on the mechanical motion of blood. In this embodiment, the doppler transducer can be applied anywhere along the arm or leg. The microphone detects heart sounds (e.g. opening and closing of the heart valves) from the thorax, which are well understood and enables the calculation of well defined time points of the start and end of a blood bolus.

Additionally it is further known that the pulse transit time and pulse wave velocity can be correlated to the blood pressure of an individual enabling beat-to-beat blood pressure readings. In particular, pulse wave velocity can be used to measure both relative arterial blood pressure changes and absolute arterial blood pressure via appropriate calibration techniques, as is known in the art, utilizing beat-to-beat blood pressure values.