Mechanical, structural, and physiologic differences between above and below-knee human arteries.

Peripheral Artery Disease (PAD) affects the lower extremities and frequently results in poor clinical outcomes, especially in the vessels below the knee. Understanding the biomechanical and structural characteristics of these arteries is important for improving treatment efficacy, but mechanical and structural data on tibial vessels remain limited. We compared the superficial femoral (SFA) and popliteal (PA) arteries that comprise the above-knee femoropopliteal (FPA) segment to the infrapopliteal (IPA) anterior tibial (AT), posterior tibial (PT), and fibular (FA) arteries from the same 15 human subjects (average age 52, range 42-67 years, 87 % male). Vessels were imaged using µCT, evaluated with biaxial mechanical testing and constitutive modeling, and assessed for elastin, collagen, smooth muscle cells (SMCs), and glycosaminoglycans (GAGs). IPAs were more often diseased or calcified compared to the FPAs. They were also twice smaller, 53 % thinner, and significantly stiffer than the FPA longitudinally, but not circumferentially. IPAs experienced 48 % higher physiologic longitudinal stresses (62 kPa) but 27 % lower circumferential stresses (24 kPa) and similar cardiac cycle stretch of <1.02 compared to the FPA. IPAs had lower longitudinal pre-stretch (1.12) than the FPAs (1.29), but there were no differences in the stored elastic energy during pulsation. The physiologic circumferential stiffness was similar in the above and below-knee arteries (718 kPa vs 754 kPa). Structurally, IPAs had less elastin, collagen, and GAGs than the FPA, but maintained similar SMC content. Our findings contribute to a better understanding of segment-specific human lower extremity artery biomechanics and may inform the development of better medical devices for PAD treatment. STATEMENT OF SIGNIFICANCE: Peripheral Artery Disease (PAD) in the lower extremity arteries exhibits distinct characteristics and results in different clinical outcomes when treating arteries above and below the knee. However, their mechanical, structural, and physiologic differences are poorly understood. Our study compared above- and below-knee arteries from the same middle-aged human subjects and demonstrated distinct differences in size, structure, and mechanical properties, leading to variations in their physiological behavior. These insights could pave the way for creating location-specific medical devices and treatments for PAD, offering a more effective approach to its management. Our findings provide new, important perspectives for clinicians, researchers, and medical device developers interested in treating PAD in both above- and below-knee locations.

Structural and Mechanical Properties of Human Superficial Femoral and Popliteal Arteries.

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions.

A viscoelastic constitutive model for human femoropopliteal arteries.

High failure rates present challenges for surgical and interventional therapies for peripheral artery disease of the femoropopliteal artery (FPA). The FPA's demanding biomechanical environment necessitates complex interactions with repair devices and materials. While a comprehensive understanding of the FPA's mechanical characteristics could improve medical treatments, the viscoelastic properties of these muscular arteries remain poorly understood, and the constitutive model describing their time-dependent behavior is absent. We introduce a new viscoelastic constitutive model for the human FPA grounded in its microstructural composition. The model is capable of detailing the contributions of each intramural component to the overall viscoelastic response. Our model was developed utilizing fractional viscoelasticity and tested using biaxial experimental data with hysteresis and relaxation collected from 10 healthy human subjects aged 57 to 65 and further optimized for high throughput and automation. The model accurately described the experimental data, capturing significant nonlinearity and hysteresis that were particularly pronounced circumferentially, and tracked the contribution of passive smooth muscle cells to viscoelasticity that was twice that of the collagen fibers. The high-throughput parameter estimation procedure we developed included a specialized objective function and modifications to enhance convergence for the common exponential-type fiber laws, facilitating computational implementation. Our new model delineates the time-dependent behavior of human FPAs, which will improve the fidelity of computational simulations investigating device-artery interactions and contribute to their greater physical accuracy. Moreover, it serves as a useful tool to investigate the contribution of arterial constituents to overall tissue viscoelasticity, thereby expanding our knowledge of arterial mechanophysiology. STATEMENT OF SIGNIFICANCE: The demanding biomechanical environment of the femoropopliteal artery (FPA) necessitates complex interactions with repair devices and materials, but the viscoelastic properties of these muscular arteries remain poorly understood with the constitutive model describing their time-dependent behavior being absent. We hereby introduce the first viscoelastic constitutive model for the human FPA grounded in its microstructures. This model was tested using biaxial mechanical data collected from 10 healthy human subjects between the ages of 57 to 65. It can detail the contributions of each intramural component to the overall viscoelastic response, showing that the contribution of passive smooth muscle cells to viscoelasticity is twice that of collagen fibers. The usefulness of this model as tool to better understand arterial mechanophysiology was demonstrated.

A method of assessing peripheral stent abrasiveness under cyclic deformations experienced during limb movement.

Poor outcomes of peripheral arterial disease stenting are often attributed to the inability of stents to accommodate the complex biomechanics of the flexed lower limb. Abrasion damage caused by rubbing of the stent against the artery wall during limb movement plays a significant role in reconstruction failure but has not been characterized. Our goals were to develop a method of assessing the abrasiveness of peripheral nitinol stents and apply it to several commercial devices. Misago, AbsolutePro, Innova, Zilver, SmartControl, SmartFlex, and Supera stents were deployed inside electrospun nanofibrillar tubes with femoropopliteal artery-mimicking mechanical properties and subjected to cyclic axial compression (25%), bending (90°), and torsion (26°/cm) equivalent to five life-years of severe limb flexions. Abrasion was assessed using an abrasion damage score (ADS, range 1-7) for each deformation mode. Misago produced the least abrasion and no stent fractures (ADS 3). Innova caused small abrasion under compression and torsion but large damage under bending (ADS 7). Supera performed well under bending and compression but caused damage under torsion (ADS 8). AbsolutePro produced significant abrasion under bending and compression but less damage under torsion (ADS 12). Zilver fractured under all three deformations and severely abraded the tube under bending and compression (ADS 15). SmartControl and SmartFlex fractured under all three deformations and produced significant abrasion due to strut penetration (ADS 20 and 21). ADS strongly correlated with clinical 12-month primary patency and target lesion revascularization rates, and the described method of assessing peripheral stent abrasiveness can guide device selection and development. STATEMENT OF SIGNIFICANCE: Poor outcomes of peripheral arterial disease stenting are related to the inability of stents to accommodate the complex biomechanics of the flexed lower limb. Abrasion damage caused by rubbing of the stent against the artery wall during limb movement plays a significant role in reconstruction failure but has not been characterized. Our study presents the first attempt at assessing peripheral stent abrasiveness, and the proposed method is applied to compare the abrasion damage caused by Misago, AbsolutePro, Innova, Zilver, SmartControl, SmartFlex, and Supera peripheral stents using artery-mimicking synthetic tubes and cyclic deformations equivalent to five life-years of severe limb flexions. The abrasion damage caused by stents strongly correlates with their clinical 12-month primary patency and target lesion revascularization rates, and the described methodology can be used as a cost-effective and controlled way of assessing stent performance, which can guide device selection and development.

Safe balloon inflation parameters for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Noncompressible hemorrhage is a leading cause of preventable death in civilian and military trauma populations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising method for controlling noncompressible hemorrhage, but safe balloon inflation parameters are not well defined. Our goal was to determine the balloon inflation parameters associated with benchtop flow occlusion and aortic/balloon rupture in ex vivo human aortas and test the hypothesis that optimal balloon inflation characteristics depend on systolic pressure and subject demographics. METHODS: Aortic occlusion parameters in human thoracic aortas (TAs) and abdominal aortas (AAs) from 79 tissue donors (median ± SD age, 52 ± 18 years [range, 13-75 years]; male, 52; female, 27) were recorded under 100/40, 150/40, and 200/40 mm Hg flow pressures for ER-REBOA and Coda balloons. Rupture tests were done with Coda balloons only without flow. RESULTS: In the TA, the average balloon inflation volumes and pressures resulting in 100/40 mm Hg flow occlusion were 11.7 ± 3.8 mL and 174 ± 65 mm Hg for the ER-REBOA, and 10.6 ± 4.3 mL and 94 ± 57 mm Hg for the Coda balloons. In the AA, these values were 6.2 ± 2.6 mL and 110 ± 47 mm Hg for the ER-REBOA, and 5.9 ± 2.2 mL and 71 ± 30 mm Hg for the Coda. The average balloon inflation parameters associated with aortic/Coda balloon rupture were 39.1 ± 6.5 mL and 1,284 ± 385 mm Hg in the TA, and 27.7 ± 7.7 mL and 1,410 ± 483 mm Hg in the AA. Age, sex, and systolic pressure all had significant effects on balloon occlusion and rupture parameters. CONCLUSION: Optimal balloon inflation parameters depend on anatomical, physiological, and demographic characteristics. Pressure-guided rather than volume-guided balloon inflation may reduce the risk of aortic rupture. These results can be used to help improve the safety of REBOA procedures and devices.

Calcification prevalence in different vascular zones and its association with demographics, risk factors, and morphometry.

Vascular calcification is associated with a higher incidence of cardiovascular events, but its prevalence in different vascular zones and the influence of demographics, risk factors, and morphometry remain insufficiently understood. Computerized tomography angiography scans from 211 subjects 5-93 yr old (mean age 47 ± 24 yr, 127 M/84 F) were used to build 3D vascular reconstructions and measure arterial diameters, tortuosity, and calcification volumes in six vascular zones spanning from the ascending thoracic aorta to the pelvic arteries. A machine learning random forest algorithm was used to determine the associations between calcification in each zone with demographics, risk factors, and vascular morphometry. Calcification appeared during the fourth decade of life and was present in all subjects after 65 yr. The abdominal aorta and the iliofemoral segment were the first to develop calcification, whereas the ascending thoracic aorta was the last. Demographics and risk factors explained 33-59% of the variation in calcification. Age, creatinine level, body mass index, coronary artery disease, and hypertension were the strongest contributors, whereas the effects of sex, race, tobacco use, diabetes, dyslipidemia, and alcohol and substance use disorders on calcification were small. Vascular morphometry did not directly and independently affect calcium burden. Vascular zones develop calcification asynchronously, with distal segments calcifying first. Understanding the influence of demographics and risk factors on calcium prevalence can help better understand the disease pathophysiology and may help with the early identification of patients that are at higher risk of cardiovascular events.NEW & NOTEWORTHY We investigated the prevalence of vascular calcification in different zones of the aorta and pelvic arteries using computerized tomography angiography reconstructions and have applied machine learning to determine how calcification is affected by demographics, risk factors, and morphometry. The presented data can help identify patients at higher risk of developing vascular calcification that may lead to cardiovascular events.

Mechanically tuned vascular graft demonstrates rapid endothelialization and integration into the porcine iliac artery wall.

Mechanical properties of vascular grafts likely play important roles in healing and tissue regeneration. Healthy arteries are compliant at low pressures but stiffen rapidly with increasing load, ensuring sufficient volumetric expansion without overstretching the vessel. Commercial synthetic vascular grafts are stiff and unable to expand under physiologic loads, which may result in altered hemodynamics, deleterious cellular responses, and compromised clinical performance. The goal of this study was to develop an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned nonlinear compliance and compare its healing responses to conventional expanded polytetrafluoroethylene (ePTFE) grafts in a porcine iliac artery model. Human and porcine iliac arteries were mechanically characterized, and an ENG with similar properties was created by utilizing residual strains within electrospun nanofibers. The ENG was tested for implantation suitability and implanted onto n = 5 domestic swine iliac arteries, with control ePTFE grafts implanted onto the contralateral iliac arteries. After two weeks in vivo, all iliac arteries and grafts remained patent with no signs of thrombosis or dilation. The mechanically tuned ENG implants exhibited a more confluent CD31-positive cell monolayer (1.53 ± 0.73 µm2/mm vs 0.52 ± 0.55 µm2/mm, p = 0.042) on the graft lumenal surface and a higher fraction of αSMA-positive cells (16.2 ± 8.6% vs 1.4 ± 0.7%, p = 0.018) within the graft wall than the ePTFE controls. Despite heavy cellular infiltration, the ENG retained its artery-like mechanical characteristics after two weeks in vivo. These short-term results demonstrate potential advantages of mechanically tuned biomimetic vascular grafts over standard ePTFE grafts. STATEMENT OF SIGNIFICANCE: Off-the-shelf synthetic vascular grafts are often the only option available for treating advanced stages of vascular disease. Despite significant efforts devoted to improving their biochemical characteristics, synthetic peripheral arterial grafts continue to demonstrate poor clinical outcomes leading to costly reinterventions. Here, we hypothesized that a synthetic vascular graft with elastomeric mechanical properties tuned to a healthy peripheral artery promotes better healing responses than a synthetic stiff graft. To test this hypothesis, we developed an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned mechanical properties and compared its performance to a commercial ePTFE graft in a preclinical porcine iliac artery model. Our results suggest that mechanically tuned ENGs can offer better healing responses, potentially leading to better clinical outcomes for peripheral arterial repairs.

Mechanical, structural, and physiologic differences in human elastic and muscular arteries of different ages: Comparison of the descending thoracic aorta to the superficial femoral artery.

Elastic and muscular arteries differ in structure, function, and mechanical properties, and may adapt differently to aging. We compared the descending thoracic aortas (TA) and the superficial femoral arteries (SFA) of 27 tissue donors (average 41±18 years, range 13-73 years) using planar biaxial testing, constitutive modeling, and bidirectional histology. Both TAs and SFAs increased in size with age, with the outer radius increasing more than the inner radius, but the TAs thickened 6-fold and widened 3-fold faster than the SFAs. The circumferential opening angle did not change in the TA, but increased 2.4-fold in the SFA. Young TAs were relatively isotropic, but the anisotropy increased with age due to longitudinal stiffening. SFAs were 51% more compliant longitudinally irrespective of age. Older TAs and SFAs were stiffer, but the SFA stiffened 5.6-fold faster circumferentially than the TA. Physiologic stresses decreased with age in both arteries, with greater changes occurring longitudinally. TAs had larger circumferential, but smaller longitudinal stresses than the SFAs, larger cardiac cycle stretch, 36% lower circumferential stiffness, and 8-fold more elastic energy available for pulsation. TAs contained elastin sheets separated by smooth muscle cells (SMCs), collagen, and glycosaminoglycans, while the SFAs had SMCs, collagen, and longitudinal elastic fibers. With age, densities of elastin and SMCs decreased, collagen remained constant due to medial thickening, and the glycosaminoglycans increased. Elastic and muscular arteries demonstrate different morphological, mechanical, physiologic, and structural characteristics and adapt differently to aging. While the aortas remodel to preserve the Windkessel function, the SFAs maintain higher longitudinal compliance.

Endovascular Repair of Blunt Thoracic Aortic Trauma is Associated With Increased Left Ventricular Mass, Hypertension, and Off-target Aortic Remodeling.

BACKGROUND: Aortic elasticity creates a cushion that protects the heart from pressure injury, and a recoil that helps perfuse the coronary arteries. TEVAR has become first-line therapy for many aortic pathologies including trauma, but stent-grafts stiffen the aorta and likely increase LV afterload. OBJECTIVE: Test the hypothesis that trauma TEVAR is associated with LV mass increase and adverse off-target aortic remodeling. METHODS: Computed Tomography Angiography (CTA) scans of 20 trauma TEVAR patients (17 M/3 F) at baseline [age 34.9 ±â€Š18.5 (11.4-71.5) years] and 5.1 ±â€Š3.1 (1.1-12.3) years after repair were used to measure changes in LV mass, LV mass index, and diameters and lengths of the ascending thoracic aorta (ATA). Measurements were compared with similarly-aged control patients without aortic repair (21 M/21 F) evaluated at similar follow-ups. RESULTS: LV mass and LV mass index of TEVAR patients increased from 138.5 ±â€Š39.6 g and 72.35 ±â€Š15.17 g/m2 to 173.5 ±â€Š50.1 g and 85.48 ±â€Š18.34 g/m2 at the rate of 10.03 ±â€Š12.79 g/yr and 6.25 ±â€Š10.28 g/m2/yr, whereas in control patients LV characteristics did not change. ATA diameters of TEVAR patients increased at a rate of 0.60 ±â€Š0.80 mm/yr, which was 2.4-fold faster than in controls. ATA length in both TEVAR and control patients increased at 0.58 mm/yr. Half of TEVAR patients had hypertension at follow-up compared to only 5% at baseline. CONCLUSIONS: TEVAR is associated with LV mass increase, development of hypertension, and accelerated expansile remodeling of the ascending aorta. Although younger trauma patients may adapt to these effects, these changes may be even more important in older patients with other aortic pathologies and diminished baseline cardiac function.

Constitutive modeling using structural information on collagen fiber direction and dispersion in human superficial femoral artery specimens of different ages.

Arterial mechanics plays an important role in vascular pathophysiology and repair, and advanced imaging can inform constitutive models of vascular behavior. We have measured the mechanical properties of 14 human superficial femoral arteries (SFAs) (age 12-70, mean 48±19 years) using planar biaxial extension, and determined the preferred collagen fiber direction and dispersion using multiphoton microscopy. The collagen fiber direction and dispersion were evaluated using second-harmonic generation imaging and modeled using bivariate von Mises distributions. The microstructures of elastin and collagen were assessed using two-photon fluorescence imaging and conventional bidirectional histology. The mechanical and structural data were used to describe the SFA mechanical behavior using two- and four-fiber family invariant-based constitutive models. Older SFAs were stiffer and mechanically more nonlinear than younger specimens. In the adventitia, collagen fibers were undulated and diagonally-oriented, while in the media, they were straight and circumferentially-oriented. The media was rich in collagen that surrounded the circumferentially-oriented smooth muscle cells, and the elastin was present primarily in the internal and external elastic laminae. Older SFAs had a more circumferential collagen fiber alignment, a decreased circumferential-radial fiber dispersion, but the same circumferential-longitudinal fiber dispersion as younger specimens. Both the two- and the four-fiber family constitutive models were able to capture the experimental data, and the fits were better for the four-fiber family formulation. Our data provide additional details on the SFA intramural structure and inform structurally-based constitutive models.

Comparison of morphometric, structural, mechanical, and physiologic characteristics of human superficial femoral and popliteal arteries.

Peripheral arterial disease differentially affects the superficial femoral (SFA) and the popliteal (PA) arteries, but their morphometric, structural, mechanical, and physiologic differences are poorly understood. SFAs and PAs from 125 human subjects (age 13-92, average 52±17 years) were compared in terms of radii, wall thickness, and opening angles. Structure and vascular disease were quantified using histology, mechanical properties were determined with planar biaxial extension, and constitutive modeling was used to calculate the physiologic stress-stretch state, elastic energy, and the circumferential physiologic stiffness. SFAs had larger radii than PAs, and both segments widened with age. Young SFAs were 5% thicker, but in old subjects the PAs were thicker. Circumferential (SFA: 96→193°, PA: 105→139°) and longitudinal (SFA: 139→306°, PA: 133→320°) opening angles increased with age in both segments. PAs were more diseased than SFAs and had 11% thicker intima. With age, intimal thickness increased 8.5-fold, but medial thickness remained unchanged (620µm) in both arteries. SFAs had 30% more elastin than the PAs, and its density decreased ~50% with age. SFAs were more compliant than PAs circumferentially, but there was no difference longitudinally. Physiologic circumferential stress and stiffness were 21% and 11% higher in the SFA than in the PA across all ages. The stored elastic energy decreased with age (SFA: 1.4→0.4kPa, PA: 2.5→0.3kPa). While the SFA and PA demonstrate appreciable differences, most of them are due to vascular disease. When pathology is the same, so are the mechanical properties, but not the physiologic characteristics that remain distinct due to geometrical differences.

Dysregulation of FOXO1 (Forkhead Box O1 Protein) Drives Calcification in Arterial Calcification due to Deficiency of CD73 and Is Present in Peripheral Artery Disease.

OBJECTIVE: The recessive disease arterial calcification due to deficiency of CD73 (ACDC) presents with extensive nonatherosclerotic medial layer calcification in lower extremity arteries. Lack of CD73 induces a concomitant increase in TNAP (tissue nonspecific alkaline phosphatase; ALPL), a key enzyme in ectopic mineralization. Our aim was to investigate how loss of CD73 activity leads to increased ALPL expression and calcification in CD73-deficient patients and assess whether this mechanism may apply to peripheral artery disease calcification. Approach and Results: We previously developed a patient-specific disease model using ACDC primary dermal fibroblasts that recapitulates the calcification phenotype in vitro. We found that lack of CD73-mediated adenosine signaling reduced cAMP production and resulted in increased activation of AKT. The AKT/mTOR (mammalian target of rapamycin) axis blocks autophagy and inducing autophagy prevented calcification; however, we did not observe autophagy defects in ACDC cells. In silico analysis identified a putative FOXO1 (forkhead box O1 protein) binding site in the human ALPL promoter. Exogenous AMP induced FOXO1 nuclear localization in ACDC but not in control cells, and this was prevented with a cAMP analogue or activation of A2a/2b adenosine receptors. Inhibiting FOXO1 reduced ALPL expression and TNAP activity and prevented calcification. Mutating the FOXO1 binding site reduced ALPL promoter activation. Importantly, we provide evidence that non-ACDC calcified femoropopliteal arteries exhibit decreased CD73 and increased FOXO1 levels compared with control arteries. CONCLUSIONS: These data show that lack of CD73-mediated cAMP signaling promotes expression of the human ALPL gene via a FOXO1-dependent mechanism. Decreased CD73 and increased FOXO1 was also observed in more common peripheral artery disease calcification.

Mechanical and structural changes in human thoracic aortas with age.

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and pre-stretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13 to 78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8 kPa and from 18 to 5 kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72 kPa and from 90 to 17 kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04 kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs. STATEMENT OF SIGNIFICANCE: This manuscript describes mechanical and structural changes occurring in human thoracic aortas with age, and presents material parameters for 4 commonly used constitutive models. Presented data can help better understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs.

Effects of longitudinal pre-stretch on the mechanics of human aorta before and after thoracic endovascular aortic repair (TEVAR) in trauma patients.

Thoracic endovascular aortic repair (TEVAR) has evolved as a first-line therapy for trauma patients. Most trauma patients are young, and their aortas are compliant and longitudinally pre-stretched. We have developed a method to include longitudinal pre-stretch in computational models of human thoracic aortas of different ages before and after TEVAR. Finite element models were built using computerized tomography angiography data obtained from human subjects in 6 age groups 10-69 years old. Aortic properties were determined with planar biaxial testing, and pre-stretch was simulated using a series of springs. GORE C-Tag stent-graft was computationally deployed in aortas with and without pre-stretch, and the stress-strain fields were compared. Pre-stretch had significant qualitative and quantitative effects on the aortic stress-strain state before and after TEVAR. Before TEVAR, mean intramural aortic stresses with and without pre-stretch decreased with age from 108 kPa and 83 kPa in the youngest age group, to 60 kPa in the oldest age group. TEVAR increased intramural stresses by an average of 73 ± 15 kPa and 48 ± 10 kPa for aortas with and without pre-stretch and produced high stress concentrations near the aortic isthmus. Inclusion of pre-stretch in young aortas increased intramural stresses by 30%, while in > 50-year-old subjects it did not change the results. Computational modeling of aorta-stent-graft interaction that includes pre-stretch can be instrumental for device design and assessment of its long-term performance, and in the future may help more accurately determine the stress-strain characteristics associated with TEVAR complications.

In Vivo Morphological Changes of the Femoropopliteal Arteries due to Knee Flexion After Endovascular Treatment of Popliteal Aneurysm.

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

Mechanical stresses associated with flattening of human femoropopliteal artery specimens during planar biaxial testing and their effects on the calculated physiologic stress-stretch state.

Planar biaxial testing is commonly used to characterize the mechanical properties of arteries, but stresses associated with specimen flattening during this test are unknown. We quantified flattening effects in human femoropopliteal arteries (FPAs) of different ages and determined how they affect the calculated arterial physiologic stress-stretch state. Human FPAs from 472 tissue donors (age 12-82 years, mean 53 ± 16 years) were tested using planar biaxial extension, and morphometric and mechanical characteristics were used to assess the flattening effects. Constitutive parameters for the invariant-based model were adjusted to account for specimen flattening and used to calculate the physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy for the FPAs in seven age groups. Flattened specimens were overall 12 ± 4% stiffer longitudinally and 19 ± 11% stiffer circumferentially when biaxially tested. Differences between the stress-stretch curves adjusted and non-adjusted for the effects of flattening were relatively constant across all age groups longitudinally, but increased with age circumferentially. In all age groups, these differences were smaller than the intersubject variability. Physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy were all qualitatively and quantitatively similar when calculated with and without the flattening effects. Stresses, stretches, axial force, and stored energy reduced with age, but circumferential stiffness remained relatively constant between 25 and 65 years of age suggesting a homeostatic target of 0.75 ± 0.02 MPa. Flattening effects associated with planar biaxial testing are smaller than the intersubject variability and have little influence on the calculated physiologic stress-stretch state of human FPAs.

Mechanical damage characterization in human femoropopliteal arteries of different ages.

Endovascular treatment of Peripheral Arterial Disease (PAD) is notorious for high failure rates, and interaction between the arterial wall and the repair devices plays a significant role. Computational modeling can help improve clinical outcomes of these interventions, but it requires accurate inputs of elastic and damage characteristics of the femoropopliteal artery (FPA) which are currently not available. Fresh human FPAs from n = 104 tissue donors 14-80 years old were tested using planar biaxial extension to capture elastic and damage characteristics. Damage initiation stretches and stresses were determined for both longitudinal and circumferential directions, and their correlations with age and risk factors were assessed. Two and four-fiber-family invariant-based constitutive models augmented with damage functions were used to describe stress softening with accumulating damage. In FPAs younger than 50 years, damage began accumulating after 1.51 ±â€¯0.13 and 1.49 ±â€¯0.11 stretch, or 196 ±â€¯110 kPa and 239 ±â€¯79 kPa Cauchy stress in the longitudinal and circumferential directions, respectively. In FPAs older than 50 years, damage initiation stretches and stresses decreased to 1.27 ±â€¯0.09 (106 ±â€¯52 kPa) and 1.26 ±â€¯0.09 (104 ±â€¯59 kPa), respectively. Damage manifested primarily as tears at the internal and external elastic laminae and within the tunica media layer. Higher body mass index and presence of diabetes were associated with lower damage initiation stretches and higher stresses. The selected constitutive models were able to accurately portray the FPA behavior in both elastic and inelastic domains, and properties were derived for six age groups. Presented data can help improve fidelity of computational models simulating endovascular PAD repairs that involve arterial damage. STATEMENT OF SIGNIFICANCE: This manuscript describes inelastic, i.e. damage, behavior of human femoropopliteal arteries, and provides values for three constitutive models simulating this behavior computationally. Using a set of 104 human FPAs 14-80 years old, we have investigated stress and stretch levels corresponding to damage initiation, and have studied how these damage characteristics change across different age groups. Presented inelastic arterial characteristics are important for computational simulations modeling balloon angioplasty and stenting of peripheral arterial disease lesions.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Cross-sectional pinching in human femoropopliteal arteries due to limb flexion, and stent design optimization for maximum cross-sectional opening and minimum intramural stresses.

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb flexion. One of these deformations, cross-sectional pinching, has a direct effect on blood flow, but is poorly characterized. Intra-arterial markers were deployed into n = 50 in situ cadaveric FPAs (80 ± 12 years old, 14F/11M), and limbs were imaged in standing, walking, sitting and gardening postures. Image analysis was used to measure marker openings and calculate FPA pinching. Parametric finite element analysis on a stent section was used to determine the optimal combination of stent strut amplitude, thickness and the number of struts per section to maximize cross-sectional opening and minimize intramural mechanical stress and low wall shear stress. Pinching was higher distally and increased with increasing limb flexion. In the walking, sitting and gardening postures, it was 1.16-1.24, 1.17-1.26 and 1.19-1.35, respectively. Stent strut amplitude and thickness had strong effects on both intramural stresses and pinching. Stents with a strut amplitude of 3 mm, thickness of 175 µm and 20 struts per section produced pinching and intramural stresses typical for a non-stented FPA, while also minimizing low wall shear stress areas, and ensuring a stent lifespan of at least 107 cycles. These results can help guide the development of improved devices and materials to treat peripheral arterial disease.