fig1 is a block - diagram of a preferred embodiment of a device 10 of this invention . the device includes : a . an acquisition module 20 ( note that the words “ module ” and “ unit ” are used interchangeably and have the same meaning throughout this document ), b . a preprocessing module 40 , c . an output / display module 60 , d . a processing module 80 , e . an optional communication unit 100 , and f . an optional external user terminal and / or connection to the internet cloud . the acquisition module 20 is connected to sensors for measuring at least one signal generated or associated with the passage of arterial pressure waves along the vascular tree . the number of sensors and their type are selected according to the specific requirements of a particular application . for example , shusterman &# 39 ; s application ser . no . 13 / 017 , 043 discloses accelerometer sensors and / or other microelectromechanical systems , which can be positioned in multiple locations along major blood vessels . other sensors , including sound ( microphones ), ultrasound , infrared , radio - frequency , electromagnetic , electrical impedance and other sensors , can be used for tracking arterial pressure waves . in a simple , cost - and size - minimized configuration , module 20 has only one sensor for detecting the passage of arterial pressure wave and two or three ecg electrodes , which are used for detecting the peak of the r wave or some other fiducial point in the ecg signal ( fig3 ). the fiducial point in the ecg signal provides approximate start time of the pressure wave generated by the heart contraction , as described above . in such a minimized configuration , module 20 contains ecg electrodes and sensor for detecting arterial pressure waves within a single , miniaturized unit . this miniaturized configuration is useful as a screening and first - response tool for paramedics , emergency medical personnel as well as a personal checkup tool for individuals at home or on the road . an alternative minimized configuration uses two pressure - wave sensors ( i . e ., in configuration , the 2 nd pressure - wave sensor / signal replaces the ecg sensors / signal ). by contrast , multiple sensors are required for the mapping of spatial distribution of the pressure waves , as shown in fig8 - 10 , and other applications . preprocessing module 40 filters the signals from noise and electromagnetic interference , which are unavoidable in both real - life and laboratory settings . the filtering can be implemented in the electronic circuitry ( hardware implementation ) and software / firmware ( software implementation ) and may include fixed filters , finite - impulse response ( fir ), infinite impulse response ( iir ), wavelets , kalman filter and adaptive filters . the preprocessing may also use pattern recognition techniques to separate signal from noise . power - line interference represents a well - known problem and can minimized using common - mode rejection implemented in the electronic circuitry or software . output / display unit displays the waveforms and / or filtered signals obtained from preprocessing module 40 , as well as results of processing and analysis ( e . g ., changes in arterial pressure , vasomotor activity , baroreflex , vascular elasticity ) obtained from processing module 80 . processing module 80 receives filtered signals from the preprocessing module 40 and performs at least some of the following processing and classification steps ( the specific combination of steps depends on specifics of a particular application ): a . extracts from the signals monitored parameters , including the time of the fiducial points ( e . g ., the peak of the ecg r wave , the beginning , peak and end of the pressure wave , the 1 st , 2 nd and 3 rd peaks of the pressure waves ), using amplitude and / or derivative thresholds , feature extraction , wavelets , waveform analysis , pattern recognition ( e . g ., an orthogonal linear decomposition and identification of the basis vectors or eigenvectors which are arranged in the order of their respective eigenvalues , so that the vectors corresponding to the greatest eigenvalues represent the most typical features of the pattern and are utilized as a template for feature extraction and / or detection of the waveform patterns ) and comparison with diagnostic criteria ( thresholds ); b . calibrates monitored signals and / or parameters using an individual &# 39 ; s baseline values , as described above ; c . determines characteristics of the response to intervention described above , including the magnitude , range , speed ( time length ), pattern of temporal changes ( e . g ., linear , concave up or down ), and pattern of spatial changes , as shown in fig6 - 8 ; and d . classifies an individual &# 39 ; s pattern of response to perturbation by assessing similarity and / or differences with those for the same or similar group / population of subjects . an optional communication unit 100 allows data transmission to an external user terminal ( e . g ., personal computer , computer tablet , smart phone ) and / or internet cloud . the transmission can be wireless ( using rf - communication , such as bluetooth , wi - fi , zigbee , cell - phone , etc .) or wire ( cable ) connection . the external user terminal on a pc , laptop , smart phone , tablet pc or internet cloud can be used for data display , further analysis , editing , archiving , printing and other functions . fig2 is a block - diagram of another embodiment of a device 10 of this invention . the main difference with the preferred embodiment shown in fig1 is in the external location of the processing module 80 . this configuration minimizes the size and cost of the device 10 and is appropriate for networked devices and some applications where on - site , real - time data tracking is not essential . for example , such configuration can be used in the devices , which provide tracking of patients &# 39 ; data and transmit those data to a central monitoring station using a wireless or wire - based communication . the central monitoring station can be located at a medical center or on an internet cloud ( a virtual medical center ). fig3 shows examples of sensor locations used for pilot experiments of system prototype of this invention , which includes sensors for measuring electrocardiogram ( ecg ) and 3 - axial accelerometer ( mems ) sensors . the accelerometer sensors are positioned along the main arteries ( aorta ) to register the mechanical displacements , which arise at the time of the pressure wave arrival near the sensors &# 39 ; locations . as described above , the ecg sensors are used for determining approximate start time of the pressure wave in the left ventricle by measuring a fiducial point of the ecg waveforms ( e . g ., the peak of the r wave ). fig4 and 5 show signals recorded by the ecg and pressure - wave sensors located in the vicinity of the aorta and radial artery , as well as the parameters extracted from those signals , including : a . the ( arterial - pressure ) pulse transit time ( ptt ), which is determined as the time interval between the most prominent ecg peak and the peak of the passing pressure wave , which is detected by the accelerometer sensor when the pressure wave in the aorta reaches the sensor location ; b . pressure wave amplitude ( pa ) measured as the amplitude difference between the maximum and minimum of the pressure wave ; c . amplitudes , areas , 1 st and 2 nd derivatives of the 1 st , 2 nd and 3 rd peaks of the pressure wave ( p 1 , p 2 , p 3 ), which are produced by the reflections of the pressure waves in various parts of the arterial tree ; d . time lengths and time intervals between the 1 st , 2 nd and 3 rd peaks of the pressure wave ( p 1 , p 2 , p 3 ) e . the augmentation index determined as the ratio of an absolute difference in the amplitude of the 1 st and 2 nd pressure peaks ( pa 1 and pa 2 , respectively ) over the total amplitude of the pressure wave ( pa ), as shown in formula ( 1 ). fig6 shows examples of ecg and pressure waveforms ( which are superimposed over each other ) recorded using the prototype system and sensor locations shown in fig3 . dividing the distance traveled by the pressure wave ( e . g ., from the left ventricle to accelerometer &# 39 ; s location ) by ptt yields the pressure wave velocity ( pwv ). this speed is directly proportional to arterial pressure , because the pressure wave travels faster when the pressure increases . however , pwv is also affected by vascular stiffness ; it increases when arterial walls become stiffer ( less elastic ). as disclosed in shusterman application ser . no . 13 / 017 , 043 , the changes in arterial stiffness are highly variable in peripheral arteries ( e . g ., in the finger arteries ), and this variability represents a major obstacle in the derivation of arterial pressure using the measurements obtained from peripheral arteries . however , as further disclosed in shusterman application ser . no . 13 / 017 , 043 , the arterial stiffness is essentially unchanged ( constant ) in the aorta and large vessels , which allows one to derive and track changes in arterial pressure from pressure - wave &# 39 ; s amplitude and ptt measurements obtained in the large vessels . as fig6 demonstrates , ptt becomes shorter ( i . e ., pressure wave velocity increases ), when systemic arterial pressure increases due to handgrip compared to rest ( 105 / 65 to 135 / 95 mm hg ), ptt measured between the peak of the r wave in the ecg and the peak of the pressure wave in the abdominal aorta , as measured by an accelerometer positioned at site 3 in fig3 . fig7 shows theoretically predicted shapes of relationships between the pwv and diastolic pressure for different states of vascular activity , which are elicited by different types of interventions in healthy volunteers ( roytvarf a ., shusterman v . a large - scale , energetic model of cardiovascular homeostasis predicts dynamics of arterial pressure in humans . ieee transactions on biomedical engineering 2008 , 55 : 407 - 418 ). the relaxed state of vascular activity is elicited by aerobic exercise ( e . g ., on a bicycle or treadmill ), whereas the contracted state of vascular activity is elicited by an isometric muscle contraction during valsalva maneuver . in particular , the experimental and theoretical study by roytvarf and shusterman cited above showed that a qualitatively similar relationship ( to that shown in fig6 ) exists between pwv and mean arterial pressure ( mp ), which is calculated as : where sp is the systolic pressure and dp is the diastolic pressure . thus , the weight of diastolic pressure is two - fold greater than that of systolic pressure , which suggests that the shapes of the relationships between pwv and mp is similar to those for pwv and dp . these theoretical predictions are shown in fig6 . fig8 shows the following locations or sites ( which are marked by circles ) for tracking passage of the pressure waves in central arteries / blood vessels ( aorta , carotid arteries and subclavian arteries ): other possible sensor locations include ascending aorta , thoracic aorta , pulmonary artery , renal arteries , carotid arteries , subclavian arteries , radial arteries , digital arteries , dorsalis pedis artery and its branches . the sensor locations can be changed and optimized according to setting and application specifics , age , gender , medical history diagnosis , blood vessels , or region of vascular tree being investigated . fig9 shows theoretically predicted spatial distribution of the pressure wave characteristics ( e . g ., pressure - wave arrival times , amplitudes , 1 st , 2 nd and 3 rd peak amplitude and durations ) in major arteries in a healthy individual . the distribution has a regular , uniform shape , showing that all vascular walls have similar wall composition ( elasticity ) and that there are no major non - uniformities in the diameter of blood vessel ( e . g ., caused by aneurisms or atherosclerosis ). fig1 shows theoretically predicted spatial distribution of the pressure waves in major arteries in a person with vascular abnormalities , which in contrast to those shown in fig8 , lead to a non - uniform , irregular distribution pattern of pressure wave characteristics e . g ., pressure - wave arrival times , amplitudes , 1 st , 2 nd and 3 rd peak amplitude and durations ). such non - uniform distributions are predicted for blood vessels abnormalities , which can be due to aneurisms or atherosclerosis . fig1 shows an example of a patch sensor , which incorporates two electrocardiographic sensors 1 and a sensor adapted for registering mechanical movements of the body , particularly , passage of the pressure waves 2 ( e . g ., an accelerometer , mems sensor , photoplethysmographic sensor , impedance - plethysmography sensor , voltage - clamp sensor , ultrasound sensor , etc .). the sensors are embedded within the patch material 3 , which is covered by an adhesive substance to provide good attachment to the skin surface . the patch may also contain a communication module 4 ( e . g ., bluetooth , zigbee , wi - fi , etc . ), or it can be attached to an external communication module by a cable , directly or via the cable connector . the following hypothetical example illustrates application of the present invention for testing the efficacy of a vasoactive medication ( serelaxin ) for managing acute heart failure . similarly , the present invention can be applied for testing other vasoactive medications and in other patient populations . serelaxin , recombinant human relaxin - 2 , is a vasoactive hormone that produces multiple hemodynamic effects primarily associated with vasodilation . in patients with acute heart failure ( ahf ), it increases arterial compliance , cardiac output , and renal blood flow , reduces dyspnea , and moderately decreases systemic arterial and pulmonary wedge pressures ( teerlink et al . ; relaxin in acute heart failure ( relax - ahf ) investigators . serelaxin , recombinant human relaxin - 2 , for treatment of acute heart failure ( relax - ahf ): a randomised , placebo - controlled trial . lancet 2013 ; 381 : 29 - 39 . dschietzig et al . intravenous recombinant human relaxin in compensated heart failure : a safety , tolerability , and pharmacodynamic trial . j card fail . 2009 : 182 - 90 . teichman et al . relaxin : review of biology and potential role in treating heart failure . curr heart fail rep 2010 ; 7 : 75 - 82 .) however , the magnitude of relaxin - evoked effects varies from patient to patient and is difficult to forecast in each particular case . it has been shown , for example , that improvements in dyspnea are more likely to occur in patients who have higher baseline arterial pressure . ( teerlink et al . vasodilators in acute heart failure ( ahf ): does blood pressure matter ? results from pre - relax - ahf . journal of cardiac failure 2009 ; 15 : s74 ) mechanistically , this effect is most likely determined by individual differences in baseline smooth - muscle tone ( smt ), so that more pronounced relaxin - induced vasodilation occurs in subjects with greater baseline smt , which is usually associated with higher arterial pressure . thus , by examining baseline smt , it is possible to identify ahf patients who would benefit the most from this medication and optimize the dose for each subject . in this hypothetical example , a 50 - year old patient with ahf has been given the test of the present invention to determine baseline vasomotor activity and the magnitude of the response to serelaxin , as manifested by changes in the pressure wave characteristics described in the summary of the invention . the test has shown that none of the pressure wave characteristics , including pressure wave amplitude , its area , 1 st and 2 nd derivative , pulse wave velocity , magnitude and duration of the 1 st , 2 nd , and 3 rd peaks of the pressure waves has changed after the medication . given this minimal response , administration of serelaxin has been stopped . example 2 . detection and localization of vascular abnormalities using spatio - temporal distribution of pressure waves in major arteries this hypothetical example shows application of the present invention for the detection and localization of vascular abnormalities , including atherosclerotic plagues and aneurisms . a screening procedure is conducted in a hypothetical , 60 - year old subject with arterial hypertension and arterosclerosis , using multiple accelerometers attached in vicinity of major arteries around the torso ( including the chest , abdomen and back ), as well as the neck , head and extremities , as shown in fig8 and 9 . after the initial intervention administered using an exercise stress test , the recovery of the pressure - wave characteristics described above would show any local heterogeneity ( irregularity ) detected by accelerometers positioned in the region of abdominal aorta . subsequent ultrasound tests would reveal an aortic aneurism . example 3 . differentiating atherosclerotic loss of vascular elasticity from the contractile state of the smooth muscle activity in arterial walls differentiating permanent changes in vascular elasticity due to atherosclerosis from those caused by increased smooth muscle activity is challenging . this hypothetical examples illustrates application of present invention for those purposes . in a hypothetical , 50 - year old man with arterial hypertension , an initial intervention ( exercise stress test ) produced a 10 % change in the pulse wave velocity compared with the average changes observed in the same age and sex group . a second intervention ( valsalva maneuver ) also resulted in 15 % change in those parameters compared with age / sex adjusted average values . the typical curved patterns of the relationships between the pwv and diastolic pressure were “ flattened ” ( i . e ., the curvatures were largely absent ). this led to a conclusion of pronounced atherosclerotic changes of large arteries ( as opposed to the possibility of increased vascular smooth - muscle tone ). example 4 . diagnosis the state of vascular autonomic nervous system activity the vascular activity is controlled by the sympathetic nervous system . it is important to evaluate the magnitude of the sympathetic modulation in patients with hypertension , heart failure , ischemic and non - ischemic cardiomyopathies , and other cardiovascular disorders . in this hypothetical example , a 30 year old female underwent initial interventions ( exercise test and valsalva maneuver ), and her pwv / diastolic pressure relationship showed a 50 % greater curvature and magnitude of changed compared with age and sex - adjusted mean values . this led to the conclusion of increased sympathetic modulation and administration of sympatholytic medications . example 5 . predicting and tracking the effectiveness of vasoactive medications in patients with hypertension arterial hypertension is a significant public health problem , which afflicts 40 million americans . although a number of medications are used for treatment of high blood pressure , finding an optimal combination of drugs , dosage and frequency is challenging . this hypothetical example illustrates application of the present invention for the assessment of the efficiency of vasoactive medications in subjects with hypertension . in a 40 - year old female with arterial hypertension , an initial intervention ( exercise stress test ) was inclusive . a subsequent exercise and intake of vasorelaxants showed a significant decrease in diastolic pressure compared with the 1 st test . this confirmed the efficiency of vasorelaxants for controlling blood pressure in this individual . nothing in the above and attached descriptions is meant to limit the present invention to any specific materials , geometry , or orientation of elements . many modifications are contemplated within the scope of the present invention and will be apparent to those skilled in the art . the embodiments disclosed herein were presented by way of example only and should not be used to limit the scope of the invention . whereas particular aspects of the method of the present invention and particular embodiments of the invention have been described for purposes of illustration , it will be appreciated by those skilled in the art that numerous variations of the details may be made without departing from the invention as described in the appended claims .
method and system for evaluating arterial pressure waves , vascular properties , as well as for diagnostic , physiological and pharmacological testing using various combinations of the following data acquisition and processing steps : 1 . perturbing arterial pressure from its steady state . 2 . measuring the dynamics of at least one parameter related to the passage of arterial pressure waves along blood vessels . 3 . characterizing the magnitude and functional relation of changes in parameters described above in relation to changes in blood pressure during its displacement from and / or return to the steady state . 4 . classifying the individual functional relation described above with a databank of parameters / functional relations for different states of vasomotor activity .