Simulation of Vitreous Traction Force and Flow Rate of High Speed Dual-Pneumatic 7500 Cuts Per Minute Vitrectomy Probes.

Purpose: To develop methods to simulate vitreous flow and traction during vitrectomy and qualify these methods using laboratory measurements. Methods: Medium viscosity and phase treatment were adjusted to represent vitreous (Eulerian two-phase flow) or saline solution (single-phase Navier-Stokes flow). Retinal traction was approximated using a one-way fluid-structure interaction simulating cut vitreous volume coupled to a structural simulation of elastic stretching of a cylinder representing vitreous fibers entrained in the flow. Results: Simulated saline solution flow decreased, but vitreous flow increased with increasing cut rate, consistent with experimental trends observed for the 50/50 duty cycle mode. Traction simulations reproduced all trends in variation of traction force with changes in conditions. Simulations reproduced the majority of traction measurements within experimental error. Conclusions: A scientific basis is provided for understanding how flow and traction vary with operational parameters. This model-based analysis serves as a "virtual lab" to determine optimal system settings to maximize flow efficiency while reducing traction. Translational Relevance: The model provides a better understanding regarding how instrument settings can help control a vitrectomy procedure so that it can be made as efficient as possible (maximizing the rate of vitreous removal) while at the same time being made as safe as possible (minimizing retinal traction).

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 tissue's 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 aorta's 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.

FSI Simulations of Pulse Wave Propagation in Human Abdominal Aortic Aneurysm: The Effects of Sac Geometry and Stiffness.

This study aims to quantify the effects of geometry and stiffness of aneurysms on the pulse wave velocity (PWV) and propagation in fluid-solid interaction (FSI) simulations of arterial pulsatile flow. Spatiotemporal maps of both the wall displacement and fluid velocity were generated in order to obtain the pulse wave propagation through fluid and solid media, and to examine the interactions between the two waves. The results indicate that the presence of abdominal aortic aneurysm (AAA) sac and variations in the sac modulus affect the propagation of the pulse waves both qualitatively (eg, patterns of change of forward and reflective waves) and quantitatively (eg, decreasing of PWV within the sac and its increase beyond the sac as the sac stiffness increases). The sac region is particularly identified on the spatiotemporal maps with a region of disruption in the wave propagation with multiple short-traveling forward/reflected waves, which is caused by the change in boundary conditions within the saccular region. The change in sac stiffness, however, is more pronounced on the wall displacement spatiotemporal maps compared to those of fluid velocity. We conclude that the existence of the sac can be identified based on the solid and fluid pulse waves, while the sac properties can also be estimated. This study demonstrates the initial findings in numerical simulations of FSI dynamics during arterial pulsations that can be used as reference for experimental and in vivo studies. Future studies are needed to demonstrate the feasibility of the method in identifying very mild sacs, which cannot be detected from medical imaging, where the material property degradation exists under early disease initiation.

Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI).

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by harmonic motion imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking radiofrequency signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the measured Young's modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI = 2.62  ±  0.41 kPa, compared to EMechTesting = 4.2  ±  2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens.

Quantification of Arterial Wall Inhomogeneity Size, Distribution, and Modulus Contrast Using FSI Numerical Pulse Wave Propagation.

Changes in aortic wall material properties, such as stiffness, have been shown to accompany onset and progression of various cardiovascular pathologies. Pulse Wave velocity (PWV) and propagation along the aortic wall have been shown to depend on the wall stiffness (i.e. stiffer the wall, higher the PWV), and can potentially enhance the noninvasive diagnostic techniques. Conventional clinical methods involve a global examination of the pulse traveling between femoral and carotid arteries, to provide an average PWV estimate. Such methods may not prove effective in detecting wall focal changes as entailed by a range of cardiovascular diseases. A two-way-coupled fluid-structure interaction (FSI) simulation study of pulse wave propagation along inhomogeneous aortas with focal stiffening and softening has previously proved the model reliable. In this study, simulations are performed on inhomogeneous aortic walls with hard inclusions of different numbers, size and modulus in order to further characterize the effects of focal hardening on pulse wave propagation. Spatio-temporal maps of the wall displacement were used to analyze the regional pulse wave propagations and velocities. The findings showed that the quantitative markers -such as PWVs and r2 s on the pre-inclusion forward, reflected and post-inclusion waves, and the width of the standing wave- as well as qualitative markers -such as diffracted reflection zone versus single reflection wave- allow the successful and reliable distinction between the changes in inclusion numbers, size and modulus. Future studies are needed to incorporate the wall softening and physiologically-relevant wall inhomogeneities such as those seen in calcifications or aneurysms.

Ex Vivo characterization of canine liver tissue viscoelasticity after high-intensity focused ultrasound ablation.

The potential of elasticity imaging to detect high-intensity focused ultrasound (HIFU) lesions on the basis of their distinct biomechanical properties is promising. However, information on the quantitative mechanical properties of the tissue and the optimal intensity at which to determine the best contrast parameters is scarce. In this study, fresh canine livers were ablated using combinations of ISPTA intensities of 5.55, 7.16 and 9.07 kW/cm(2) and durations of 10 and 30 s ex vivo, resulting in six groups of ablated tissues. Biopsy samples were then interrogated using dynamic shear mechanical testing within the range of 0.1-10 Hz to characterize the tissue's post-ablation viscoelastic properties. All mechanical parameters were found to be frequency dependent. Compared with unablated cases, all six groups of ablated tissues had statistically significant higher complex shear modulus and shear viscosity. However, among the ablated groups, both complex shear modulus and shear viscosity were found to monotonically increase in groups 1-4 (5.55 kW/cm(2) for 10 s, 7.16 kW/cm(2) for 10 s, 9.07 kW/cm(2) for 10 s, and 5.55 kW/cm(2) for 30 s, respectively), but to decrease in groups 5 and 6 (7.16 kW/cm(2) for 30 s, and 9.07 kW/cm(2) for 30 s, respectively). For groups 5 and 6, the temperature was expected to exceed the boiling point, and therefore, the decreased stiffening could be due to the compromised integrity of the tissue microstructure. Future studies will entail estimation tissue mechanical properties in vivo and perform real-time monitoring of tissue alterations during ablation.

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.

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.

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.

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.

Quantifying the interfibrillar spacing and fibrillar orientation of the aortic extracellular matrix using histology image processing: toward multiscale modeling.

An essential part of understanding tissue microstructural mechanics is to establish quantitative measures of the morphological changes. Given the complex, highly localized, and interactive architecture of the extracellular matrix, developing techniques to reproducibly quantify the induced microstructural changes has been found to be challenging. In this paper, a new method for quantifying the changes in the fibrillar organization is developed using histology images. A combinatorial frequency-spatial image processing approach was developed based on the Fourier and Hough transformations of histology images to measure interfibrillar spacing and fibrillar orientation, respectively. The method was separately applied to the inner and outer wall thickness of native- and elastin-isolated aortic tissues under different loading states. Results from both methods were interpreted in a complementary manner to obtain a more complete understanding of morphological changes due to tissue deformations at the microscale. The observations were consistent in quantifying the observed morphological changes during tissue deformations and in explaining such changes in terms of tissue-scale phenomena. The findings of this study could pave the way for more rigorous modeling of structure-property relationships in soft tissues, with implications extendable to cardiovascular constitutive modeling and tissue engineering.

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.

Detection of Aortic Wall Inclusion 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.

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.

An efficient technique for adjusting and maintaining specific hydration levels in soft biological tissues in vitro.

Elucidating how mechanics is affected by hydration in soft biological tissues is critical for understanding the potential effects of diseases where tissue extracellular matrix (ECM) is altered. The ability to control ECM water content is necessary for studying hydration-dependent tissue mechanics and for minimizing confounding effects caused by differences in tissue water content among specimens. In this paper, we describe an approach to adjust and maintain water content using a two-stage hydration technique, in order to overcome unique challenges faced in mechanical testing of biological tissues. Bovine aortic tissue was selected to demonstrate the approach. A liquid phase approach using PEG solutions allowed for efficient initial adjustment of tissue hydration. This was followed by a vapor phase approach using a humidity chamber for maintaining stable water content for a defined test duration of 45 min. Incubation in PEG solution brought bovine aortic tissue samples to equilibrium water content in approximately 6 h, much more efficiently than using a humidity chamber alone. Characteristic relationships between tissue water content and PEG concentration as well as relative humidity were obtained. It was found that PEG concentrations ranging from 0 to 40% had an inverse relationship with tissue water content ranging from 80 to 380%, which corresponded to relative humidities between 53 and 99%.

On the multiscale modeling of heart valve biomechanics in health and disease.

Theoretical models of the human heart valves are useful tools for understanding and characterizing the dynamics of healthy and diseased valves. Enabled by advances in numerical modeling and in a range of disciplines within experimental biomechanics, recent models of the heart valves have become increasingly comprehensive and accurate. In this paper, we first review the fundamentals of native heart valve physiology, composition and mechanics in health and disease. We will then furnish an overview of the development of theoretical and experimental methods in modeling heart valve biomechanics over the past three decades. Next, we will emphasize the necessity of using multiscale modeling approaches in order to provide a comprehensive description of heart valve biomechanics able to capture general heart valve behavior. Finally, we will offer an outlook for the future of valve multiscale modeling, the potential directions for further developments and the challenges involved.