Alexey Kamenskiy

Passive biaxial mechanical properties and in vivo axial pre-stretch of the diseased human femoropopliteal and tibial arteries.

Surgical and interventional therapies for atherosclerotic lesions of the infrainguinal arteries are notorious for high rates of failure. Frequently, this leads to expensive reinterventions, return of disabling symptoms or limb loss. Interaction between the artery and repair material likely plays an important role in reconstruction failure, but data describing the mechanical properties and functional characteristics of human femoropopliteal and tibial arteries are currently not available. Diseased superficial femoral (SFA, n = 10), popliteal (PA, n = 8) and tibial arteries (TA, n = 3) from 10 patients with critical limb ischemia were tested to determine passive mechanical properties using planar biaxial extension. All specimens exhibited large nonlinear deformations and anisotropy. Under equibiaxial loading, all arteries were stiffer in the circumferential direction than in the longitudinal direction. Anisotropy and longitudinal compliance decreased distally, but circumferential compliance increased, possibly to maintain a homeostatic multiaxial stress state. Constitutive parameters for a four-fiber family invariant-based model were determined for all tissues to calculate in vivo axial pre-stretch that allows the artery to function in the most energy efficient manner while also preventing buckling during extremity flexion. Calculated axial pre-stretch was found to decrease with age, disease severity and more distal arterial location. Histological analysis of the femoropopliteal artery demonstrated a distinct sub-adventitial layer of longitudinal elastin fibers that appeared thicker in healthier arteries. The femoropopliteal artery characteristics and properties determined in this study may assist in devising better diagnostic and treatment modalities for patients with peripheral arterial disease.

Effects of age on the physiological and mechanical characteristics of human femoropopliteal arteries

Surgical and interventional therapies for peripheral artery disease (PAD) are notorious for high rates of failure. Interactions between the artery and repair materials play an important role, but comprehensive data describing the physiological and mechanical characteristics of human femoropopliteal arteries are not available. Fresh femoropopliteal arteries were obtained from 70 human subjects (13-79 years old), and in situ vs. excised arterial lengths were measured. Circumferential and longitudinal opening angles were determined for proximal superficial femoral, proximal popliteal and distal popliteal arteries. Mechanical properties were assessed by multi-ratio planar biaxial extension, and experimental data were used to calculate physiological stresses and stretches, in situ axial force and anisotropy. Verhoeff-Van Gieson-stained axial and transverse arterial sections were used for histological analysis. Most specimens demonstrated nonlinear deformations and were more compliant longitudinally than circumferentially. In situ axial pre-stretch decreased 0.088 per decade of life. In situ axial force and axial stress also decreased with age, but circumferential physiological stress remained constant. Physiological circumferential stretch decreased 55-75% after 45 years of age. Histology demonstrated a thickened external elastic lamina with longitudinally oriented elastin that was denser in smaller, younger arteries. Axial elastin likely regulates axial pre-stretch to help accommodate the complex deformations required of the artery wall during locomotion. Degradation and fragmentation of elastin as a consequence of age, cyclic mechanical stress and atherosclerotic arterial disease may contribute to decreased in situ axial pre-stretch, predisposing to more severe kinking of the artery during limb flexion and loss of energy-efficient arterial function.

Three-dimensional bending, torsion and axial compression of the femoropopliteal artery during limb flexion

High failure rates of femoropopliteal artery reconstruction are commonly attributed to complex 3D arterial deformations that occur with limb movement. The purpose of this study was to develop a method for accurate assessment of these deformations. Custom-made stainless-steel markers were deployed into 5 in situ cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were acquired with each limb in the straight and acutely bent states. Image segmentation and 3D reconstruction allowed comparison of the relative locations of each intra-arterial marker position for determination of the arterys bending, torsion and axial compression. After imaging, each artery was excised for histological analysis using Verhoeff-Van Gieson staining. Femoropopliteal arteries deformed non-uniformly with highly localized deformations in the proximal superficial femoral artery, and between the adductor hiatus and distal popliteal artery. The largest bending (11±3-6±1 mm radius of curvature), twisting (28±9-77±27°/cm) and axial compression (19±10-30±8%) were registered at the adductor hiatus and the below knee popliteal artery. These deformations were 3.7, 19 and 2.5 fold more severe than values currently reported in the literature. Histology demonstrated a distinct sub-adventitial layer of longitudinally oriented elastin fibers with intimal thickening in the segments with the largest deformations. This endovascular intra-arterial marker technique can quantify the non-uniform 3D deformations of the femoropopliteal artery during knee flexion without disturbing surrounding structures. We demonstrate that 3D arterial bending, torsion and compression in the flexed lower limb are highly localized and are substantially more severe than previously reported.

Nonlinear Mechanical Behavior of The Human Common, External, and Internal Carotid Arteries In Vivo

BACKGROUND The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA), and internal (ICA) carotid arteries over the cardiac cycle in vivo. METHODS Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA, and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semiautomatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and strain-induced stiffness of the arterial wall (stiffening in response to the increase of intraluminal blood pressure) for each patient. RESULTS The diameter and wall thickness of the segments (CCA, ECA, and ICA) of the carotid bifurcation were found to decrease and strain-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25 ± 7 to 63 ± 23 kPa (CCA), from 22 ± 7 to 57 ± 19 kPa (ECA), and from 28 ± 8 to 67 ± 23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40 ± 0.25 to 1.50 ± 2.05 MPa (CCA), from 0.49 ± 0.34 to 1.14 ± 0.52 MPa (ECA), and from 0.68 ± 0.31 to 1.51 ± 0.69 MPa (ICA). The strain-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared with end-diastole. CONCLUSIONS The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries--CCA, ECA and ICA--exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.

Comparative Analysis of the Biaxial Mechanical Behavior of Carotid Wall Tissue and Biological and Synthetic Materials Used for Carotid Patch Angioplasty

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n  =  1), Dacron (n  =  2), bovine pericardium (n  =  10), autogenous greater saphenous vein (n  =  10), and autogenous external jugular vein (n  =  9) with the wall of the common carotid artery (n  =  18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy.

In vivo three-dimensional blood velocity profile shapes in the human common, internal, and external carotid arteries

OBJECTIVE True understanding of carotid bifurcation pathophysiology requires a detailed knowledge of the hemodynamic conditions within the arteries. Data on carotid artery hemodynamics are usually based on simplified, computer-based, or in vitro experimental models, most of which assume that the velocity profiles are axially symmetric away from the carotid bulb. Modeling accuracy and, more importantly, our understanding of the pathophysiology of carotid bifurcation disease could be considerably improved by more precise knowledge of the in vivo flow properties within the human carotid artery. The purpose of this work was to determine the three-dimensional pulsatile velocity profiles of human carotid arteries. METHODS Flow velocities were measured over the cardiac cycle using duplex ultrasonography, before and after endarterectomy, in the surgically exposed common (CCA), internal (ICA), and external (ECA) carotid arteries (n = 16) proximal and distal to the stenosis/endarterectomy zone. These measurements were linked to a standardized grid across the flow lumina of the CCA, ICA, and ECA. The individual velocities were then used to build mean three-dimensional pulsatile velocity profiles for each of the carotid artery branches. RESULTS Pulsatile velocity profiles in all arteries were asymmetric about the arterial centerline. Posterior velocities were higher than anterior velocities in all arteries. In the CCA and ECA, velocities were higher laterally, while in the ICA, velocities were higher medially. Pre- and postendarterectomy velocity profiles were significantly different. After endarterectomy, velocity values increased in the common and internal and decreased in the external carotid artery. CONCLUSIONS The in vivo hemodynamics of the human carotid artery are different from those used in most current computer-based and in vitro models. The new information on three-dimensional blood velocity profiles can be used to design models that more closely replicate the actual hemodynamic conditions within the carotid bifurcation. Such models can be used to further improve our understanding of the pathophysiologic processes leading to stroke and for the rational design of medical and interventional therapies.

Effects of Carotid Artery Stenting on Arterial Geometry

BACKGROUND The role of carotid artery stenting (CAS) for the treatment of carotid artery disease continues to evolve, despite higher stroke and restenosis risks for CAS compared with conventional open endarterectomy. Understanding the effects of CAS on arterial geometry, which strongly influence hemodynamics and wall mechanics, can assist in better stratifying the inherent risk of CAS to individual patients. STUDY DESIGN Fifteen consecutive patients undergoing CAS had pre- and post-stenting CT angiograms. These images were used to reconstruct the 3-dimensional geometries of the bilateral carotid arteries from their origin to the skull base. Quantitative assessment of the carotid bifurcation angle, cross-sectional area, tortuosity and artery length, were compared pre- and post-stenting. Plaque volume and calcification were also measured. Mathematical models were devised to determine the mechanisms of CAS-induced geometric changes, and their mechanical and hemodynamic significances. RESULTS Major and moderate changes in arterial tortuosity and elongation were seen in 5 (33%) patients. Characteristics most associated with the development of CAS-induced geometric changes were stenoses located in the internal carotid artery distal to the carotid bulb, circumferential distribution of plaque, and plaque calcification. Modeling did not demonstrate substantial alterations in wall shear stress due to geometric changes, but did show considerable increases in arterial wall axial stress. CONCLUSIONS Carotid artery stenting can produce geometric changes to the artery that promote favorable conditions for complications and recurrent disease. Patients with circumferential, highly calcified plaques that are located relatively distal in the internal carotid artery are most likely to have post-stenting geometric changes.

Age and disease-related geometric and structural remodeling of the carotid artery

BACKGROUND Carotid artery geometry has been suggested as a risk factor for atherosclerotic carotid artery disease (ACD). Although normal aging and development of disease can both lead to geometric changes in the artery, whether geometric changes in a given artery actually predispose to disease or are just a consequence of remodeling during aging is unclear. We investigated carotid artery geometric changes with aging to identify geometric features associated with the presence of ACD. METHODS Carotid artery geometry was quantified by measuring carotid artery diameter, tortuosity, and bifurcation angle using three-dimensional reconstructions of thin-section computed tomography angiography scans in 15 healthy individuals (average age, 43 ± 18 years; range, 15-64 years). The same geometric features were measured in 17 patients (68 ± 10 years old) with unilateral ACD. Geometric features associated with presence of ACD were determined by using the nondiseased contralateral carotid artery as an intrinsic control. Elastin-stained carotid arteries were analyzed to assess age-related structural changes in 12 deceased individuals. RESULTS Increases were noted in bulb diameter (0.64 mm), bifurcation angle (10°), and tortuosity of the common carotid (CCA; 0.03) and internal carotid arteries (ICA; 0.04) for every decade of life. Density and continuity of circumferential and longitudinal elastin in the CCA and ICA decreased with age. Compared with normal carotid arteries, those with ACD demonstrated larger bulb diameters (P = .001) but smaller bifurcation angles (P = .001). CCA tortuosity (P = .038) increased in ACD arteries compared with normal carotid arteries, but ICA tortuosity was decreased (P = .026). CONCLUSIONS With increasing age, bulb diameter, tortuosity, and bifurcation angle increases in carotid arteries. These geometric changes may be related to degradation and fragmentation of intramural elastin. Arteries with atherosclerotic occlusive disease demonstrate decreased ICA tortuosity and smaller bifurcation angles compared with nondiseased carotid arteries.

IN SITU LONGITUDINAL PRE-STRETCH IN THE HUMAN FEMOROPOPLITEAL ARTERY

UNLABELLED In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14-80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=-0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r=-0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users. STATEMENT OF SIGNIFICANCE This work studies in situ longitudinal pre-stretch (LPS) in the human femoropopliteal artery. LPS has a fundamental role in arterial mechanics, but is rather poorly studied due to lack of direct in vivo measurement method. We have investigated LPS in the n=148 human femoropopliteal arteries in the context of subject demographics and risk factors, and structural and physiologic characteristics of the artery. Our results demonstrate that LPS reduces with age due to degradation and fragmentation of intramural elastin. LPS may serve as an energy reserve for adaptive remodeling, and reduction of LPS can be accelerated in tobacco users.

Finite Element Model of the Patched Human Carotid

Introduction: The hemodynamic effects of carotid artery patching are not well known. Our objective was to develop a fluid-solid finite element model of the endarterectomized and patched carotid artery. Methods: Hyperelastic materials parameters were determined from studies of 8 cadaveric carotids. Blood flow characteristics were based on intraoperative data from a patient undergoing endarterectomy. Wall shear stress, cyclic strain and effective stress were computed as hemodynamic parameters with known association with endothelial injury, neointimal hyperplasia abd atherogenesis. Results: Low wall shear stress, high cyclic strain and high effective stress were identified diffusely in the carotid bulb, at the margins around the patch and in the flow divider. Conclusion: Endarterectomy and Polytetrafluoroethylene patching produce considerable abnormalities in the hemodynamics of the repaired carotid. Advanced mechanical modeling can be used to evaluate different carotid revascularization approaches to obtain optimized biomechanical and hemodynamic results for the care of patients with carotid bifurcation disease.