Danial Shahmirzadi

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.

Detection of aortic wall inclusions using regional pulse wave propagation and velocity in silico

Monitoring of the regional stiffening of the arterial wall may prove important in the diagnosis of various vascular pathologies. The pulse wave velocity (PWV) along the aortic wall has been shown to be dependent on the wall stiffness and has played a fundamental role in a range of diagnostic methods. Conventional clinical methods involve a global examination of the pulse traveling between two remote sites, e.g. femoral and carotid arteries, to provide an average PWV estimate. However, the majority of vascular diseases entail regional vascular changes and therefore may not be detected by a global PWV estimate. In this paper, a fluid-structure interaction study of straight-geometry aortas was carried out to examine the effects of regional stiffness changes on PWV. Five homogeneous aortas with increasing wall stiffness as well as two aortas with soft and hard inclusions were considered. In each case, spatio-temporal maps of the wall motion were used to analyze the regional pulse wave propagation. On the homogeneous aortas, increasing PWVs were found to increase with the wall moduli (R2 = 0.9988), indicating the reliability of the model to accurately represent the wave propagation. On the inhomogeneous aortas, formation of reflected and standing waves was observed at the site of the hard and soft inclusions, respectively. Neither the hard nor the soft inclusion had a significant effect on the velocity of the traveling pulse beyond the inclusion site, which supported the hypothesis that a global measurement of the average PWV could fail to detect regional abnormalities.

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.

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.

A viscoelastic property study in canine liver before and after HIFU ablation in vitro

Elasticity imaging techniques have shown great potential in detecting High Intensity Focused Ultrasound (HIFU) lesions based on their distinct biomechanical properties. However, quantitative tissue viscoelastic properties and the optimal power to obtain the best contrast parameters remain scarce. In the present study, fresh canine livers were ablated ex vivo using six different acoustic powers and time durations, covering an energy range of 80-330 J. Biopsy samples were then extracted and examined, using rheometry, to obtain the viscoelastic properties post-ablation in vitro. All mechanical parameters were found to be frequency dependent. Both the shear complex modulus and viscosity exhibited monotonic increase for the first 4 groups (80-240 J), relatively lower HIFU powers. Similar parameters from groups 5-6 (300-330 J) showed relative decrease, still higher than unablated group 0. The tangent of the stress-strain phase shift was found to vary from unablated group 0 to ablated groups 1-6. However, no measurable difference amongst the ablated groups was found. Decreased stiffening at high powers compared to the baseline could likely be due to compromised structural integrity in the pulverized tissue well beyond the boiling point. The findings here can be used to optimize the efficient monitoring and treatment of tumors using any thermally-based methods where strong tissue damage is expected and/or warranted, respectively.

Energy-based constitutive modelling of local material properties of canine aortas

This study aims at determining the in vitro anisotropic mechanical behaviour of canine aortic tissue. We specifically focused on spatial variations of these properties along the axis of the vessel. We performed uniaxial stretch tests on canine aortic samples in both circumferential and longitudinal directions, as well as histological examinations to derive the tissues fibre orientations. We subsequently characterized a constitutive model that incorporates both phenomenological and structural elements to account for macroscopic and microstructural behaviour of the tissue. We showed the two fibre families were oriented at similar angles with respect to the aortas axis. We also found significant changes in mechanical behaviour of the tissue as a function of axial position from proximal to distal direction: the fibres become more aligned with the aortic axis from 46° to 30°. Also, the linear shear modulus of media decreased as we moved distally along the aortic axis from 139 to 64 kPa. These changes derived from the parameters in the nonlinear constitutive model agreed well with the changes in tissue structure. In addition, we showed that isotropic contribution, carried by elastic lamellae, to the total stress induced in the tissue decreases at higher stretch ratios, whereas anisotropic stress, carried by collagen fibres, increases. The constitutive models can be readily used to design computational models of tissue deformation during physiological loading cycles. The findings of this study extend the understanding of local mechanical properties that could lead to region-specific diagnostics and treatment of arterial diseases.

A Multifaceted Device for Discreetly Acquiring Natural Behaviors of Children with Autism

Autism is a multifaceted neurological disorder that affects the four fundamental areas of sensory processing, communication mechanisms, social interaction skills, and whole child/self-esteem. The underlying mechanisms and symptoms of the disorder have been shown to largely vary from patient to patient, and therefore, a durable, effective therapy is best achieved through multifaceted, multidisciplinary approaches that allow a direct assessment of each individual’s behavior, both quantitatively and qualitatively. The aim of this project was to simulate, design, manufacture, and assess a device that can help cultivate sensory, social, communication, and motor skills in autistic children while being able to extract data of the child’s behavior that could be used by the therapist. Critical components of the toy involve auditory and visual stimulation, as well as interactive mechanisms to promote development. The most important features of the toy are hidden cameras that discreetly monitor the child’s reactions in order to provide analytical feedback mechanisms, allowing parents, caregivers, or therapists to monitor and evaluate the child’s learning and therapy. The performance of the toy was examined on 17 children with autism at two specialized centers for child with developmental disorders. The results showed that the device was found satisfactory by the majority of children as assessed by their willingness to spend time accomplishing the tasks on the device, as well as by captured videos of their natural reactions throughout. Furthermore, improved performance was observed on the same population of children who were tested multiple times, indicating the potential use of the toy for therapeutic and learning purposes.