Pulse Wave Imaging in Carotid Artery Stenosis Human Patients in Vivo.

Carotid stenosis involves narrowing of the lumen in the carotid artery potentially leading to a stroke, which is the third leading cause of death in the United States. Several recent investigations have found that plaque structure and composition may represent a more direct biomarker of plaque rupture risk compared with the degree of stenosis. In this study, pulse wave imaging was applied in 111 (n = 11, N = 13 plaques) patients diagnosed with moderate (>50%) to severe (>80%) carotid artery stenosis to investigate the feasibility of characterizing plaque properties based on the pulse wave-induced arterial wall dynamics captured by pulse wave imaging. Five (n = 5 patients, N = 20 measurements) healthy volunteers were also imaged as a control group. Both conventional and high-frame-rate plane wave radiofrequency imaging sequences were used to generate piecewise maps of the pulse wave velocity (PWV) at a single depth along stenotic carotid segments, as well as intra-plaque PWV mapping at multiple depths. Intra-plaque cumulative displacement and strain maps were also calculated for each plaque region. The Bramwell-Hill equation was used to estimate the compliance of the plaque regions based on the PWV and diameter. Qualitatively, wave convergence, elevated PWV and decreased cumulative displacement around and/or within regions of atherosclerotic plaque were observed and may serve as biomarkers for plaque characterization. Intra-plaque mapping revealed the potential to capture wave reflections between calcified inclusions and differentiate stable (i.e., calcified) from vulnerable (i.e., lipid) plaque components based on the intra-plaque PWV and cumulative strain. Quantitatively, one-way analysis of variance indicated that the pulse wave-induced cumulative strain was significantly lower (p < 0.01) in the moderately and severely calcified plaques compared with the normal controls. As expected, compliance was also significantly lower in the severely calcified plaques regions compared with the normal controls (p < 0.01). The results from this pilot study indicated the potential of pulse wave imaging coupled with strain imaging to differentiate plaques of varying stiffness, location and composition. Such findings may serve as valuable information to compensate for the limitations of currently used methods for the assessment of stroke risk.

A Low-Power, Low-Cost Ingestible and Wearable Sensing Platform to Measure Medication Adherence and Physiological Signals.

In this paper, we present a novel Digital Medicines program used for reviewing medication adherence. The program is comprised of an ingestible sensor embedded inside medication and a wearable sensor or patch worn on the skin of the patient. The ingestible sensor activates upon contact with gastric fluids and communicates information about the ingested drug to the patch. Adherence patterns and other physiological markers measured by the system are made available to patients, physicians, and caregivers via mobile and web interfaces. The paper focuses on the wearable sensor hardware and measurement features used to provide a more comprehensive view of the patient's health centered around and contextualized by adherence patterns. This is achieved using efficient, high-performance signal processing algorithms implemented on a low-power platform. Results from bench and clinical testing are presented to demonstrate the performance of adherence, heart rate, step counts, and body angle measurements.

Noninvasive Evaluation of Varying Pulse Pressures in vivo Using Brachial Sphymomanometry, Applanation Tonometry, and Pulse Wave Ultrasound Manometry.

The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r2 < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r2 = 0.68 and 0.87, respectively). PWUM provides a low-cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites.

Assessment of arterial stiffness in periodontitis using a novel pulse wave imaging methodology.

AIM: We investigated the cross-sectional relationship between periodontal status and arterial stiffness, assessed through a novel Pulse Wave Imaging methodology. METHODS: Eighty volunteers were enrolled (39% male, age range 24-78 years) and 33 pairs were formed of periodontitis patients/periodontally healthy controls, matched by age and gender. A full-mouth periodontal examination was performed and the degree of stiffness of the right and left carotid arteries was assessed by measuring pulse wave velocity (PWV) and the uniformity in pulse wave propagation (R2 ). Wilcoxon signed-rank tests for paired observations were used to compare periodontitis patients and healthy controls. Univariate and multivariate analyses were performed to analyze the association between PWV and R2 and potential explanatory variables. RESULTS: Patients with periodontitis had a statistically significantly lower uniformity in wave propagation (R2 ) than controls (p = .01), but PWV did not differ between the two groups. Univariate analysis showed a significant negative association between R2 and periodontitis, body mass index and smoking; periodontitis remained statistically associated with R2 in the multivariate analyses. CONCLUSIONS: Patients with periodontitis and no established cardiovascular disease presented with lower degree of uniformity in the transmission of the pulse wave through the carotid arteries, suggesting an association between periodontitis and arterial stiffness/functional alterations.

An inverse approach to determining spatially varying arterial compliance using ultrasound imaging.

The mechanical properties of arteries are implicated in a wide variety of cardiovascular diseases, many of which are expected to involve a strong spatial variation in properties that can be depicted by diagnostic imaging. A pulse wave inverse problem (PWIP) is presented, which can produce spatially resolved estimates of vessel compliance from ultrasound measurements of the vessel wall displacements. The 1D equations governing pulse wave propagation in a flexible tube are parameterized by the spatially varying properties, discrete cosine transform components of the inlet pressure boundary conditions, viscous loss constant and a resistance outlet boundary condition. Gradient descent optimization is used to fit displacements from the model to the measured data by updating the model parameters. Inversion of simulated data showed that the PWIP can accurately recover the correct compliance distribution and inlet pressure under realistic conditions, even under high simulated measurement noise conditions. Silicone phantoms with known compliance contrast were imaged with a clinical ultrasound system. The PWIP produced spatially and quantitatively accurate maps of the phantom compliance compared to independent static property estimates, and the known locations of stiff inclusions (which were as small as 7 mm). The PWIP is necessary for these phantom experiments as the spatiotemporal resolution, measurement noise and compliance contrast does not allow accurate tracking of the pulse wave velocity using traditional approaches (e.g. 50% upstroke markers). Results from simulations indicate reflections generated from material interfaces may negatively affect wave velocity estimates, whereas these reflections are accounted for in the PWIP and do not cause problems.

Performance assessment of Pulse Wave Imaging using conventional ultrasound in canine aortas ex vivo and normal human arteries in vivo.

The propagation behavior of the arterial pulse wave may provide valuable diagnostic information for cardiovascular pathology. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound imaging-based technique capable of mapping multiple wall motion waveforms along a short arterial segment over a single cardiac cycle, allowing for the regional pulse wave velocity (PWV) and propagation uniformity to be evaluated. The purpose of this study was to improve the clinical utility of PWI using a conventional ultrasound system. The tradeoff between PWI spatial and temporal resolution was evaluated using an ex vivo canine aorta (n = 2) setup to assess the effects of varying image acquisition and signal processing parameters on the measurement of the PWV and the pulse wave propagation uniformity r2. PWI was also performed on the carotid arteries and abdominal aortas of 10 healthy volunteers (24.8 ± 3.3 y.o.) to determine the waveform tracking feature that would yield the most precise PWV measurements and highest r2 values in vivo. The ex vivo results indicated that the highest precision for measuring PWVs ~ 2.5 - 3.5 m/s was achieved using 24-48 scan lines within a 38 mm image plane width (i.e. 0.63 - 1.26 lines/mm). The in vivo results indicated that tracking the 50% upstroke of the waveform would consistently yield the most precise PWV measurements and minimize the error in the propagation uniformity measurement. Such findings may help establish the optimal image acquisition and signal processing parameters that may improve the reliability of PWI as a clinical measurement tool.

3D-Printed Tissue-Mimicking Phantoms for Medical Imaging and Computational Validation Applications.

Abdominal aortic aneurysm (AAA) is a permanent, irreversible dilation of the distal region of the aorta. Recent efforts have focused on improved AAA screening and biomechanics-based failure prediction. Idealized and patient-specific AAA phantoms are often employed to validate numerical models and imaging modalities. To produce such phantoms, the investment casting process is frequently used, reconstructing the 3D vessel geometry from computed tomography patient scans. In this study the alternative use of 3D printing to produce phantoms is investigated. The mechanical properties of flexible 3D-printed materials are benchmarked against proven elastomers. We demonstrate the utility of this process with particular application to the emerging imaging modality of ultrasound-based pulse wave imaging, a noninvasive diagnostic methodology being developed to obtain regional vascular wall stiffness properties, differentiating normal and pathologic tissue in vivo. Phantom wall displacements under pulsatile loading conditions were observed, showing good correlation to fluid-structure interaction simulations and regions of peak wall stress predicted by finite element analysis. 3D-printed phantoms show a strong potential to improve medical imaging and computational analysis, potentially helping bridge the gap between experimental and clinical diagnostic tools.

Mapping the longitudinal wall stiffness heterogeneities within intact canine aortas using Pulse Wave Imaging (PWI) ex vivo.

The aortic stiffness has been found to be a useful independent indicator of several cardiovascular diseases such as hypertension and aneurysms. Existing methods to estimate the aortic stiffness are either invasive, e.g. catheterization, or yield average global measurements which could be inaccurate, e.g., tonometry. Alternatively, the aortic pulse wave velocity (PWV) has been shown to be a reliable marker for estimating the wall stiffness based on the Moens-Korteweg (M-K) formulation. Pulse Wave Imaging (PWI) is a relatively new, ultrasound-based imaging method for noninvasive and regional estimation of PWV. The present study aims at showing the application of PWI in obtaining localized wall mechanical properties by making PWV measurements on several adjacent locations along the ascending thoracic to the suprarenal abdominal aortic trunk in its intact vessel form. The PWV estimates were used to calculate the regional wall modulus based on the M-K relationship and were compared against conventional mechanical testing. The findings indicated that for the anisotropic aortic wall, the PWI estimates of the modulus are smaller than the circumferential modulus by an average of -32.22% and larger than the longitudinal modulus by an average of 25.83%. Ongoing work is focused on the in vivo applications of PWI in normal and pathological aortas with future implications in the clinical applications of the technique.

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study.

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r(2) as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s(-1), respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r(2) in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r(2)) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics.

Pulse wave imaging of the human carotid artery: an in vivo feasibility study.

Noninvasive quantification of regional arterial stiffness, such as measurement of the pulse wave velocity (PWV), has been shown to be of high clinical importance. Pulse wave imaging (PWI) has been previously developed by our group to visualize the propagation of the pulse wave along the aorta and to estimate the regional PWV. The objective of this paper is to determine the feasibility of PWI in the human carotid artery in vivo. The left common carotid arteries of eight (n = 8) healthy volunteers (male, age 27 + 4 years old) were scanned in a long-axis view, with a 10-MHz linear-array transducer. The beam density of the scan was reduced to 16 beams within an imaging width of 38 mm. The frame rate of ultrasound imaging was therefore increased to 1127 Hz at an image depth of 25 mm. The RF ultrasound signals were then acquired at a sampling rate of 40 MHz and used to estimate the velocity of the arterial wall using a 1-D cross-correlationbased speckle tracking method. The sequence of the wall velocity images at different times depicts the propagation of the pulse wave in the carotid artery from the proximal to distal sides. The regional PWV was estimated from the spatiotemporal variation of the wall velocities and ranged from 4.0 to 5.2 m/s in eight (n = 8) normal subjects, in agreement with findings reported in the literature. PWI was thus proven feasible in the human carotid artery, and may be proven useful for detecting vascular disease through mapping the pulse wave and estimating the regional PWV in the carotid artery.

Pulse-wave propagation in straight-geometry vessels for stiffness estimation: theory, simulations, phantoms and in vitro findings.

Pulse wave imaging (PWI) is an ultrasound-based method for noninvasive characterization of arterial stiffness based on pulse wave propagation. Reliable numerical models of pulse wave propagation in normal and pathological aortas could serve as powerful tools for local pulse wave analysis and a guideline for PWI measurements in vivo. The objectives of this paper are to (1) apply a fluid-structure interaction (FSI) simulation of a straight-geometry aorta to confirm the Moens-Korteweg relationship between the pulse wave velocity (PWV) and the wall modulus, and (2) validate the simulation findings against phantom and in vitro results. PWI depicted and tracked the pulse wave propagation along the abdominal wall of canine aorta in vitro in sequential Radio-Frequency (RF) ultrasound frames and estimates the PWV in the imaged wall. The same system was also used to image multiple polyacrylamide phantoms, mimicking the canine measurements as well as modeling softer and stiffer walls. Finally, the model parameters from the canine and phantom studies were used to perform 3D two-way coupled FSI simulations of pulse wave propagation and estimate the PWV. The simulation results were found to correlate well with the corresponding Moens-Korteweg equation. A high linear correlation was also established between PWV² and E measurements using the combined simulation and experimental findings (R² = 0.98) confirming the relationship established by the aforementioned equation.

Performance assessment and optimization of Pulse Wave Imaging (PWI) in ex vivo canine aortas and in vivo normal human arteries.

The amplitude, velocity, and morphology of the arterial pulse wave may all provide valuable diagnostic information for cardiovascular pathology. Pulse Wave Imaging (PWI) is an ultrasound-based method developed by our group to noninvasively visualize and map the spatio-temporal variations of the pulse wave-induced vessel wall motion. Because PWI is capable of acquiring multiple wall motion waveforms successively along an imaged arterial segment over a single cardiac cycle in vivo, the regional morphological changes, amplitudes, and velocity (i.e. pulse wave velocity, or PWV) of the pulse wave can all be evaluated. In this study, an ex vivo setup was used to assess the effects of varying PWI image acquisition variables (beam density/frame rate and scanning orientation) and signal processing methods (beam sweep compensation scheme and waveform feature tracking) on the PWV estimation in order to validate the optimal parameters. PWI was also performed on the carotid arteries and abdominal aortas of six healthy volunteers for identification of several salient features of the waveforms over the entire cardiac cycle that may aid in assessing the morphological changes of the pulse wave. The ex vivo results suggest that the PWI temporal resolution is more important for PWV estimation than the PWI spatial resolution, and also that the reverse scanning orientation (i.e. beam sweeping direction opposite the direction of fluid flow) is advantageous due to higher precision and less dependence on the frame rate. In the in vivo waveforms, the highest precision PWV measurements were obtained by tracking the 50% upstroke of the waveforms. Finally, the dicrotic notch, reflected wave, and several inflection points were qualitatively identified in the carotid and aortic anterior wall motion waveforms and shown in one representative subject.

In-vivo Pulse Wave Imaging for arterial stiffness measurement under normal and pathological conditions.

Numerous studies have identified arterial stiffening as a strong indicator of cardiovascular pathologies such as hypertension and abdominal aortic aneurysm (AAA). Pulse Wave Imaging (PWI) is a novel, noninvasive ultrasound-based method to quantify regional arterial stiffness by measuring the velocity of the pulse wave that propagates along arterial walls after each left ventricular contraction. The PWI method employs 1D cross-correlation speckle tracking to compute axial incremental displacements, then tracks the position of the displacement wave in the anterior wall of the vessel to estimate pulse wave velocity (PWV). PWI has been validated on straight tube aortic phantoms and aortas of healthy humans as well as normal and AAA murine models. This paper presents and compares preliminary PWI results from normal, hypertensive, and AAA human subjects. PWV was computed in select cases from each subject category. The measured PWV values in hypertensive (N = 5) and AAA (N = 2) subjects were found to be significantly higher than in normal subjects (N = 8). In all subjects, the spatio-temporal profile and waveform morphologies of the pulse wave were generated from the displacement data for visualization and qualitative evaluation of the pulse wave propagation. While the waveforms were found to maintain roughly the same shape in normal subjects, those in the AAA and most hypertensive cases changed drastically along the imaged aortic segment, suggesting non-uniform wall mechanical properties.