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The aim of this study was to determine whether specific three-dimensional aortic shape features, extracted via statistical shape analysis (SSA), correlate with the development of thoracic ascending aortic dissection (TAAD) risk and associated aortic hemodynamics. Thirty-one patients followed prospectively with ascending thoracic aortic aneurysm (ATAA), who either did (12 patients) or did not (19 patients) develop TAAD, were included in the study, with aortic arch geometries extracted from computed tomographic angiography (CTA) imaging. Arch geometries were analyzed with SSA, and unsupervised and supervised (linked to dissection outcome) shape features were extracted with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), respectively. We determined PLS-DA to be effective at separating dissection and no-dissection patients (p=0.0010), with decreased tortuosity and more equal ascending and descending aortic diameters associated with higher dissection risk. In contrast, neither PCA nor traditional morphometric parameters (maximum diameter, tortuosity, or arch volume) were effective at separating dissection and no-dissection patients. The arch shapes associated with higher dissection probability were supported with hemodynamic insight. Computational fluid dynamics (CFD) simulations revealed a correlation between the PLS-DA shape features and wall shear stress (WSS), with higher maximum WSS in the ascending aorta associated with increased risk of dissection occurrence. Our work highlights the potential importance of incorporating higher dimensional geometric assessment of aortic arch anatomy in TAAD risk assessment, and in considering the interdependent influences of arch shape and hemodynamics as mechanistic contributors to TAAD occurrence.

BackgroundBleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability.ObjectiveTo develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population.MethodsCross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy.ResultsThe final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%).ConclusionsBased on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.

BackgroundBlebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.MethodsBlebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.ResultsThin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%.ConclusionsNot all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.

OBJECTIVE: To assess ascending aortic distensibility and build geometry and distensibility-based patient-specific stress distribution maps in patients sustaining type A aortic dissection (TAAD) using pre-dissection non-invasive imaging. METHODS: Review of charts from patients undergoing surgical repair of TAAD (n=351) led to the selection of a subset population (n=7) with two or more pre-dissection CTAs and echocardiograms at least one year prior to dissection. Ascending aortic wall biomechanical properties (aortic strain, distensibility and stiffness) were compared to age and size matched non-dissected non-aneurysmal controls. Patient-specific aortic strain served as an input in aortic geometry-based simulated three-dimensional reconstructions to generate longitudinal and circumferential wall stress maps. Inspection of peri-operative dissection scans and intraoperative visual examination confirmed primary tear locations. RESULTS: Pre-dissection echocardiography revealed ascending aortas of patients sustaining TAAD to exhibit decreased aortic wall strain (14.50 ± 1.13% vs 8.49 ± 1.08%; p < 0.01), decreased distensibility (4.26 ± 0.44 vs 2.39 ± 0.33 10(−6)cm(2)dyne(−1); p < 0.01), increased stiffness (3.84 ± 0.24 vs 7.48 ± 1.05; p < 0.001), and increased longitudinal wall stress (246 ± 22 vs 172 ± 37 kPa; p < 0.01). There was no significant difference in circumferential wall stress. Pre-dissection CTA models revealed overlap between regions of increased longitudinal wall stress and primary tear sites. CONCLUSIONS: Using pre-dissection imaging, we identified increased stiffness and longitudinal wall stress in ascending aortas of dissection patients. Patient-specific imaging-derived biomechanical property maps like these may be instrumental toward designing better prediction models of aortic dissection potential.

Biomechanical failure of the artery wall can lead to rupture, a catastrophic event with a high rate of mortality. Thus, there is a pressing need to understand failure behavior of the arterial wall. Uniaxial testing remains the most common experimental technique to assess tissue failure properties. However, the relationship between intrinsic failure parameters of the tissue and measured uniaxial failure properties is not fully established. Furthermore, the effect of the experimental variables, such as specimen shape and boundary conditions, on the measured failure properties is not well understood. We developed a finite element model capable of recapitulating pre-failure and post-failure uniaxial biomechanical response of the arterial tissue specimen. Intrinsic stiffness, strength and fracture toughness of the vessel wall tissue were used as the input material parameters to the model. Two uniaxial testing protocols were considered: a conventional setup with a rectangular specimen held at the grips by cardboard inserts, and the other used a dogbone specimen with soft foam inserts at the grips. Our computational study indicated negligible differences in the peak stress and post-peak mechanical behavior between these two testing protocols. It was also found that the tissue experienced only modest localized failure until higher levels of applied stretch beyond the peak stress. A robust cohesive model was capable of modeling the post-peak biomechanical response, which was primarily governed by tissue fracture toughness. Our results suggest that the post-peak region, in conjunction with the peak stress, must be considered to evaluate the complete biomechanical failure behavior of the soft tissue.

Right ventricular (RV) remodeling and longitudinal fiber reorientation in the setting of pulmonary hypertension (PH) affects ventricular structure and function, eventually leading to RV failure. Characterizing the kinematics of myocardial fibers helps better understanding the underlying mechanisms of fiber realignment in PH. In the current work, high-frequency ultrasound imaging and structurally-informed finite element (FE) models were employed for an exploratory evaluation of the stretch-induced kinematics of RV fibers. Image-based experimental evaluation of fiber kinematics in porcine myocardium revealed the capability of affine assumptions to effectively approximate myofiber realignment in the RV free wall. The developed imaging framework provides a noninvasive modality to quantify transmural RV myofiber kinematics in large animal models. FE modeling results demonstrated that chronic pressure overload, but not solely an acute rise in pressures, results in kinematic shift of RV fibers towards the longitudinal direction. Additionally, FE simulations suggest a potential protective role for concentric hypertrophy (increased wall thickness) against fiber reorientation, while eccentric hypertrophy (RV dilation) resulted in longitudinal fiber realignment. Our study improves the current understanding of the role of different remodeling events involved in transmural myofiber reorientation in PH. Future experimentations are warranted to test the model-generated hypotheses.

BackgroundBlebs are rupture risk factors in intracranial aneurysms (IAs), but their prevalence, distribution, and associations with clinical factors as well as their causes and effects on aneurysm vulnerability remain unclear.MethodsA total of 122 blebs in 270 IAs selected for surgery were studied using patient-specific vascular reconstructions from 3D angiographic images. Bleb geometry, location on the aneurysm, and frequency of occurrence in aneurysms at different locations were analyzed. Associations between gender, age, smoking, hypertension, hormone therapy, dental infection, and presence of blebs were investigated.ResultsOf all aneurysms with blebs, 77% had a single bleb and 23% had multiple blebs. Only 6% of blebs were at the neck, while 46% were in the body and 48% in the dome. Aneurysms with blebs were larger (pConclusionsBlebs are common in IAs, and most aneurysms harboring blebs have a single bleb. Blebs in the aneurysm neck are rare, but they are equally common in the body and dome. The presence of blebs in IAs was associated with dental infection, and negatively associated with hormone replacement therapy.

Rotator cuff tear propagation is multifactorial and may be due to localized changes in mechanical properties from tendon remodeling based on the inhomogeneous stresses experienced by a tendon with a tear. The objective of this study was to investigate the effect of localized tendon remodeling on tear propagation for simulated supraspinatus tendon tears. A validated computational model of a supraspinatus tendon using subject-specific geometry and material properties with a 1 cm wide anterior tear was used. The medial edge of the supraspinatus tendon was displaced 5 mm to induce tear propagation and cohesive elements were used to model tear propagation. Four remodeling scenarios were investigated: (1) Baseline (no remodeling), (2) Positive remodeling (increased fiber stiffness) and (3) Negative remodeling (decreased fiber stiffness) at tear tips, and (4) Negative remodeling along the medial-lateral tear edge. Output parameters included the amount of tear propagation, critical load to propagate the tear, and maximum principal stress at the tear tips. Positive remodeling at the tear tips resulted in the largest amount of tear propagation (18.4 mm), highest peak maximum principal stress (25.2 MPa), and lowest critical load to propagate the tear (249N). Conversely, negative remodeling at the tear tips resulted in the least amount of tear propagation (16 mm), lowest peak maximum principal stress (17.6 MPa) and highest critical load to propagate the tear (278N). Overall, remodeling at the tear tips has the greatest effect on tear propagation. Therefore, a better method for clinicians to measure tendon stiffness at the tear tips would be helpful to improve outcome of patients.

Rotator cuff tendons undergo degeneration with age, which could have an impact on tear propagation. The objective of this study was to predict tear propagation for different levels of tissue degeneration using an experimentally validated finite element model of a supraspinatus tendon. It was hypothesized that greater amounts of degeneration will result in tear propagation at lower loads than tendons with less degeneration. Using a previously-validated computational model of supraspinatus tendon, 1-cm tears were introduced in the anterior, middle, and posterior thirds of the tendon. Cohesive elements were assigned subject-specific failure properties to model tear propagation, and tendon degeneration ranging from "minimal" to "severe" was modeled by modifying its mechanical properties. Tears in tendons with severe degeneration required the smallest loads to propagate (122-207 N). Posterior tears required greater loads compared to middle and anterior tears at all levels of degeneration. Stress and strain required for tear propagation decreased substantially with degeneration, ranging from 8.5 MPa and 32.6% strain for minimal degeneration and 0.6 MPa and 4.5% strain for severe degeneration. Overall, this work indicates that greater amounts of tendon degeneration lead to greater risk of tear propagation, supporting the need for early detection and treatment of rotator cuff tears.

High lethality of aortic dissection necessitates accurate predictive metrics for dissection risk assessment. The not infrequent incidence of dissection at aortic diameters

Rotator cuff tears remain a significant clinical problem with a high incidence rate and severe clinical burden. Previous computational models developed to study rotator cuff tears have not modeled tissue damage and tear propagation. The objective of this study was to predict tear propagation for various combinations of tear size and location using an experimentally validated finite element model of supraspinatus tendon. It was hypothesized that larger rotator cuff tears propagate at lower loads than smaller tears, and that posterior tears require higher loads to propagate than anterior tears. Using a previously validated computational model of supraspinatus tendon, tears of size 0.5–1.5 cm were introduced to the tendon geometry in the anterior, middle, and posterior tendon thirds. Cohesive elements were assigned subject-specific failure properties and used to model tissue damage and tear propagation. A displacement of 5 mm was applied to the medial tendon edge to induce tear propagation. Model outputs included critical load required to propagate the tear, and principal stress and maximum principal strain at the anterior and posterior tear tips. For all tear sizes, posterior tears required the highest loads to propagate (247–567 N). Anterior tears generally required the least load to propagate (171–280 N). Stress and strain were larger on the articular side (maximum 33.9% articular strain vs 27.8% bursal strain). Overall, larger tears located in the anterior supraspinatus tendon that interrupt the rotator cable are most at risk for tear propagation, and should be carefully followed by clinicians when considering treatment options.

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue. Motivated by this need, we developed a finite element based three-dimensional structural model of the lamellar units of the ATA media that directly incorporates the collagen fiber microarchitecture. The fiber architecture was computer generated utilizing network features, namely fiber orientation distribution, intersection density and areal concentration, obtained from image analysis of multiphoton microscopy images taken from human aneurysmal ascending thoracic aortic media specimens with bicuspid aortic valve (BAV) phenotype. Our model reproduces the typical J-shaped constitutive response of the aortic wall tissue. We found that the stress state in the non-fibrous matrix was homogeneous until the collagen fibers were recruited, but became highly heterogeneous after that event. The degree of heterogeneity was dependent upon local network architecture with high stresses observed near disrupted fibers. The magnitude of non-fibrous matrix stress at higher stretch levels was negatively correlated with local fiber density. The localized stress concentrations, elucidated by this model, may be a factor in the degenerative changes in aneurysmal ATA tissue.

Type A Aortic Dissection (TAAD) is a life-threatening condition involving delamination of ascending aortic media layers. While current clinical guidelines recommend surgical intervention for aneurysm diameter > 5.5 cm, high incidence of TAAD in patients below this diameter threshold indicates the pressing need for improved evidence-based risk prediction metrics. Construction of such metrics will require the knowledge of the biomechanical failure properties of the aortic wall tissue under biaxial loading conditions. We utilized a fiber-level finite element based structural model of the aortic tissue to quantify the relationship between aortic tissue strength and physiologically relevant biaxial stress state for nonaneurysmal and aneurysmal patient cohorts with tricuspid aortic valve phenotype. We found that the model predicted strength of the aortic tissue under physiologic biaxial loading conditions depends on the stress biaxiality ratio, defined by the ratio of the longitudinal and circumferential components of the tissue stress. We determined that predicted biaxial tissue strength is statistically similar to its uniaxial circumferential strength below biaxiality ratios of 0.68 and 0.69 for nonaneurysmal and aneurysmal cohorts, respectively. Beyond this biaxiality ratio, predicted biaxial strength for both cohorts reduced drastically to a magnitude statistically similar to its longitudinal strength. We identified fiber-level failure mechanisms operative under biaxial stress state governing aforementioned tissue failure behavior. These findings are an important first step towards the development of mechanism-based TAAD risk assessment metrics for early identification of high-risk patients.

Although uniaxial tensile testing is commonly used to evaluate failure properties of vascular tissue, there is no established protocol for specimen shape or gripping method. Large percentages of specimens are reported to fail near the clamp and can potentially confound the studies, or, if discarded will result in sample waste. The objective of this study is to identify sample geometry and clamping conditions that can achieve consistent failure in the midregion of small arterial specimens, even for vessels from older individuals. Failure location was assessed in 17 dogbone specimens from human cerebral and sheep carotid arteries using soft inserts. For comparison with commonly used protocols, an additional 22 rectangular samples were tested using either sandpaper or foam tape inserts. Midsample failure was achieved in 94% of the dogbone specimens, while only 14% of the rectangular samples failed in the midregion, the other 86% failing close to the clamps. Additionally, we found midregion failure was more likely to be abrupt, caused by cracking or necking. In contrast, clamp failure was more likely to be gradual and included a delamination mode not seen in midregion failure. Hence, this work provides an approach that can be used to obtain consistent midspecimen failure, avoiding confounding clamp-related artifacts. Furthermore, with consistent midregion failure, studies can be designed to image the failure process in small vascular samples providing valuable quantitative information about changes to collagen and elastin structure during the failure process.

Exposure following pelvic organ prolapse repair has been observationally associated with wrinkling of the implanted mesh. The purpose of this study was to quantify the impact of variable boundary conditions on the out-of-plane deformations of mesh subjected to tensile loading. Using photogrammetry and surface curvature analyses, deformed geometries were accessed for two commercially available products. Relative to standard clamping methods, the amount of out-of-plane deformation significantly increased when point loads were introduced to simulate suture fixation in-vivo. These data support the hypothesis that regional increases in the concentration of mesh potentially enhance the host’s foreign body response, leading to exposure.

Nerve blocks are frequently performed by anesthesiologists to control pain. For sciatic nerve blocks, the optimal placement of the needle tip between its paraneural sheath and epineurial covering is challenging, even under ultrasound guidance, and frequently results in nerve puncture. We performed needle penetration tests on cadaveric isolated paraneural sheath (IPS), isolated nerve (IN), and the nerve with overlying paraneural sheath (NPS), and quantified puncture force requirement and fracture toughness of these specimens to assess their role in determining the clinical risk of nerve puncture. We found that puncture force (123 ± 17 mN) and fracture toughness (45.48 ± 9.72 J m−2) of IPS was significantly lower than those for NPS (1440 ± 161 mN and 1317.46 ± 212.45 Jm−2, respectively), suggesting that it is not possible to push the tip of the block needle through the paraneural sheath only, without pushing it into the nerve directly, when the sheath is lying directly over the nerve. Results of this study provide a physical basis for tangential placement of the needle as the ideal situation for local anesthetic deposition, as it allows for the penetration of the sheath along the edge of the nerve without entering the epineurium.

We recently reported a mechanistic model to link micro-architectural information to the delamination strength (Sd) of human ascending thoracic aorta (ATA). That analysis demonstrated that the number density (N) and failure energy (Uf) of the radially-oriented collagen fibers contribute to the Sd of both aneurysmal (ATAA) and non-aneurysmal (CTRL-ATA) aortic tissue. Among the set of ATAA samples, we studied specimens from patients displaying bicuspid (BAV) and tricuspid aortic valve (TAV) morphologic phenotypes. Results from our prior work were based on the assumption that the Uf was independent of dissection direction. In the current study, we excluded that assumption and hypothesized that Uf correlates with the Sd of ATAA. To test the hypothesis, we used previously-reported experimentally-determined Sd measurements and N of radially-oriented collagen fibers as input in our validated mechanistic model to calculate Uf for BAV-ATAA, TAV-ATAA and CTRL-ATA tissue specimens. The results of our analysis revealed that Uf is significantly lower for both BAV-ATAA and TAV-ATAA compared to CTRL-ATA cases, and does not differ between BAV-ATAA and TAV-ATAA. Furthermore, we found that Uf is consistent between circumferential-radial and longitudinal-radial planes in either of BAV-ATAA, TAV-ATAA or CTRL-ATA specimens. These findings employ a novel mechanistic model to increase our understanding of the putative interrelationship between biomechanical properties, extracellular matrix biology, and failure energy of aortic dissection.

Rotator cuff tears are a common problem in patients over the age of 50 yr. Tear propagation is a potential contributing factor to the failure of physical therapy for treating rotator cuff tears, thus requiring surgical intervention. However, the evolution of tears within the rotator cuff is not well understood yet. The objective of this study is to establish a computational model to quantify initiation of tear propagation in the supraspinatus tendon and examine the effect of tear size and location. A 3D finite element (FE) model of the supraspinatus tendon was constructed from images of a healthy cadaveric tendon. A tear of varying length was placed at six different locations within the tendon. A fiber-reinforced Mooney–Rivlin material model with spatial variation in material properties along the anterior–posterior (AP) axis was utilized to obtain the stress state of the computational model under uniaxial stretch. Material parameters were calibrated by comparing computational and experimental stress–strain response and used to validate the computational model. The stress state of the computational model was contrasted against the spatially varying material strength to predict the critical applied stretch at which a tear starts propagating further. It was found that maximum principal stress (as well as the strain) was localized at the tips of the tear. The computed critical stretch was significantly lower for the posterior tip of the tear than for the anterior tip suggesting a propensity to propagate posteriorly. Onset of tear propagation was strongly correlated with local material strength and stiffness in the vicinity of the tear tip. Further, presence of a stress-shielded zone along the edges of the tear was observed. This study illustrates the complex interplay between geometry and material properties of tendon up to the initiation of tear propagation. Future work will examine the evolution of tears during the propagation process as well as under more complex loading scenarios.

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovascular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber micro-architecture, obtained in a parallel study from multi-photon microscopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence.

Synthetic polypropylene meshes were designed to restore pelvic organ support for women suffering from pelvic organ prolapse; however, the FDA released two notifications regarding the potential complications associated with mesh implantation. Our aim was to characterize the structural properties of Restorelle and UltraPro subjected to uniaxial tension along perpendicular directions, and then model the tensile behavior of these meshes utilizing a co-rotational finite element model, with an imbedded linear or fiber-recruitment local stress-strain relationship. Both meshes exhibited highly nonlinear stress-strain behavior; Restorelle had no significant differences between the two perpendicular directions, while UltraPro had a 93% difference in the low (initial) stiffness (p=0.009) between loading directions. Our model predicted that early alignment of the mesh segments in the loading direction and subsequent stretching could explain the observed nonlinear tensile behavior. However, a nonlinear stress-strain response in the stretching regime, that may be inherent to the mesh segment, was required to better capture experimental results. Utilizing a nonlinear fiber recruitment model with two parameters A and B, we observed improved agreement between the simulations and the experimental results. An inverse analysis found A=120 MPa and B=1.75 for Restorelle (RMSE=0.36). This approach yielded A=30 MPa and B=3.5 for UltraPro along one direction (RMSE=0.652), while the perpendicular orientation resulted in A=130 MPa and B=4.75 (RMSE=4.36). From the uniaxial protocol, Restorelle was found to have little variance in structural properties along these two perpendicular directions; however, UltraPro was found to behave anisotropically.