ASME Conference Presenter Attendance Policy and Archival Proceedings

2013;():V01AT00A001. doi:10.1115/SBC2013-NS1A.

This online compilation of papers from the ASME 2013 Summer Bioengineering Conference (SBC2013) represents the archival version of the Conference Proceedings. According to ASME’s conference presenter attendance policy, if a paper is not presented at the Conference, the paper will not be published in the official archival Proceedings, which are registered with the Library of Congress and are submitted for abstracting and indexing. The paper also will not be published in The ASME Digital Collection and may not be cited as a published paper.

Commentary by Dr. Valentin Fuster

Abdominal Aortic Aneurysms

2013;():V01AT01A001. doi:10.1115/SBC2013-14237.

Abdominal Aortic Aneurysm (AAA) is the gradual and irreversible local widening of the distal region of the aorta. If undetected or untreated the intramural stress can exceed the strength of the aneurysm wall causing the structure to rupture. Upon rupture, AAA has a 90% mortality rate. It has been hypothesized, and shown in some studies, that regions of elevated stress of the AAA wall may be linked to sites of AAA rupture. In order for Finite Element Analysis (FEA) to be successfully used as a clinical tool, to aid in AAA rupture prediction, it is crucial that the mechanics of both the AAA wall and intraluminal thrombus (ILT) are described accurately. At present it is unclear whether ILT increases or decreases the rupture risk of AAA. This may be due to the lack of available data which can accurately describe its behaviour in vivo. A recent review of AAA mechanics explains how ‘there have been limited studies on the mechanical properties of intraluminal thrombus’. Due to the recent popularity of endovascular aneurysm repair (EVAR) the opportunities to harvest and conduct mechanical tests on this tissue are rare. This study aims to further characterize ILT using both uniaxial and biaxial test methods and where possible determine the layer and region specific mechanical properties of this material.

Commentary by Dr. Valentin Fuster
2013;():V01AT01A002. doi:10.1115/SBC2013-14403.

Aortic dissection is a life-threatening cardiovascular emergency with a high potential for death. It usually begins with an intimal tear which permits blood to enter the wall, split the media and create a false lumen, which can reenter the true lumen or exit through the adventitia causing complete rupture. A possible mechanism for dissection of ascending thoracic aortic aneurysm (ATAA) can be the occurrence of blood pressure-induced wall stresses in excess to the adhesive strength between the degenerated aortic wall layers.

Topics: Fibers , Valves , Aneurysms
Commentary by Dr. Valentin Fuster
2013;():V01AT01A003. doi:10.1115/SBC2013-14509.

Abdominal aortic aneurysm (AAA) disease is primarily a degenerative process, where rupture occurs when stress exerted on the aortic wall exceeds its failure strength. Therefore, knowledge of both the wall stress distribution and the mechanical properties of the AAA wall is required for patient specific rupture risk estimation.

Commentary by Dr. Valentin Fuster
2013;():V01AT01A004. doi:10.1115/SBC2013-14643.

Abdominal aortic aneurysm (AAA) is a permanent, localized enlargement of the abdominal aorta that accompanies disturbed blood flow, which is thought to perpetuate aneurysm progression. AAA rupture is a leading cause of death in the elderly and an exact intervention decision for this disease has always been associated with uncertainty. There is currently no medicinal treatment of AAA, however lower extremity exercise has been a proposed therapy. Specifically, elevated flow rates in the abdominal aorta, reduced retrograde flow, higher mean wall shear stress, and lower oscillatory shear index resulting from exercise have been hypothesized as beneficial in preventing or slowing AAA. Computational fluid dynamics (CFD) has recently been used to model flow conditions inside AAA with an aim to better understand the biomechanical underpinnings of this disease. Recent studies have used patient-specific computational models, however few studies have looked in detail to AAA transport topology or correlated their results with aneurysm progression data. This study aims to (1) compare the flow topology between rest and exercise conditions in patients with small AAA to understand specifically how blood transport changes from rest to exercise, and (2) compare flow parameters obtained by CFD to the aneurysm progression.

Commentary by Dr. Valentin Fuster
2013;():V01AT01A005. doi:10.1115/SBC2013-14684.

Abdominal Aortic Aneurysm (AAA), a focal enlargement of the abdominal aorta is an ongoing process that can be affected by many parameters. Among these parameters, hemodynamics and intraluminal thrombus layer (ILT) play important roles on AAA growth. It is widely accepted that hemodynamic forces (normal and shear forces) have a profound impact on the mechano-homeostasis of the arterial wall and its vascular remodeling. The role of ILT, however, remains controversial. Some studies suggest that ILT may be beneficial by shieling the weak aneurysm wall, whereas others claim that the presence of ILT can lead to immune responses that increase protease breakdown of collagen and elastin, adversely affecting wall strength. ILT is formed by the deposition of blood clots called thrombus. Thrombus formation is achieved through different mechanisms, but all research agrees that shear fluid forces are one of the key parameters for the formation and development of ILT. There are few studies to date that use these three parameters to assess the evolution of AAAs growth. Here, we explore the relation between wall shear stress (WSS), ILT and AAA expansion using longitudinal CT images from follow-up studies from 3 patients (a total of 8 scans). We used geometrical models of AAAs segmented from patient images to estimate outer surface displacement, ILT, and tissue thickness. Additionally, we used fluid dynamic data to estimate wall shear stress at peak systolic. These parameters were then used to investigate possible relationships with each other.

Commentary by Dr. Valentin Fuster
2013;():V01AT01A006. doi:10.1115/SBC2013-14837.

The current clinical management of abdominal aortic aneurysm (AAA) disease is based to a great extent on measuring the aneurysm maximum diameter to decide when timely intervention is required. Decades of clinical evidence show that aneurysm diameter is positively associated with the risk of rupture, but other parameters may also play a role in causing or predisposing the AAA to rupture. Geometric factors such as vessel tortuosity, intraluminal thrombus volume, and wall surface area are implicated in the differentiation of ruptured and unruptured AAAs. Biomechanical factors identified by means of computational modeling techniques, such as peak wall stress, have been positively correlated with rupture risk with a higher accuracy and sensitivity than maximum diameter alone. In the present work, we performed a controlled study targeted at evaluating the effect of uncertainty of the constitutive material model used for the vascular wall in the ensuing peak wall stress. Based on the outcome of this study, a second analysis was conducted based on the geometric characterization of surface curvature in two groups of aneurysm geometries, to discern which curvature metric can adequately discriminate ruptured from electively repaired AAA. The outcome of this work provides preliminary evidence on the importance of quantitative geometry characterization for AAA rupture risk assessment in the clinic.

Commentary by Dr. Valentin Fuster

Active and Reactive Soft Matter

2013;():V01AT02A001. doi:10.1115/SBC2013-14091.

We report the discovery of a fundamental morphological instability of constrained 3D microtissues induced by a positive chemomechanical feedback between actomyosindriven contraction and the mechanical stresses arising from the constraints. Using a 3D model for mechanotransduction we find that perturbations in the shape of contractile tissues grow in an unstable manner leading to formation of “necks” where tensile stresses are sufficiently large to lead to the failure of the tissue by narrowing and subsequent elongation. The origin of the failure mechanism driven by active forces we report is distinct from the seemingly similar and well studied necking phenomena observed in “passive” materials due to elastic softening. Here the instability is caused by the active contraction (extension) of the regions of the tissue where the mechanical stresses are smaller (greater) than the characteristic actomyosin stall stress of the tissue. The magnitude of the instability is shown to be determined by the level of active contractile strain, the stiffness of the ECM and the stiffness of the boundaries that constrain the tissue. A phase diagram that demarcates stable and unstable behavior of 3D tissues as a function of these material parameters is derived. The predictions of our model are verified by analyzing the necking and failure of normal human fibroblast (NHF) tissue constrained in a loopended dogbone geometry and cardiac microtissues constrained between microcantilevers. In the former case, the tissue fails first by necking of the connecting rod of the dogbone followed by failure of the toroidal loops in agreement with our 3D finite element simulations. In the latter case we find that cardiac tissue is stable against necking when the density of the extra cellular matrix is increased and when the stiffness of the supporting cantilevers is decreased, also in excellent agreement with the predictions of our model. By analyzing the time evolution of the morphology of the constrained tissues we have quantitatively determined the chemomechanical coupling parameters that characterize the generation of active stresses in these tissues. More generally, the analytical and numerical methods we have developed provide a quantitative framework to study the biomechanics of cell to cellinteractions in complex 3D environments such as morphogenesis and organogenisis.

Commentary by Dr. Valentin Fuster
2013;():V01AT02A002. doi:10.1115/SBC2013-14100.

Heart valve disease leads to approximately 300,000 heart valve replacement surgeries each year worldwide. Valvular interstitial cells (VICs) are believed to play a vital role in the repair of heart valves and also most disease processes. VICs synthesize, remodel, and repair the ECM; however, when VICs excessively differentiate to the highly contractile and synthetic myofibroblast phenotype, valvular fibrosis may ensue. Elevated mechanical stress triggers the differentiation of VICs into myofibroblasts. Transforming growth factor beta-1 (TGF-β1) is also critical for the formation of thicker stress fibers positive for α-smooth muscle actin (α-SMA), the defining characteristic of myofibroblasts.

Commentary by Dr. Valentin Fuster
2013;():V01AT02A003. doi:10.1115/SBC2013-14214.

The orientation of collagen fibers is essential for tissue mechanical functioning. Tissues are able to adapt this network to changes in the mechanical environment. Two mechanisms for this adaptation that have been proposed are cell-orientation dependent cell-traction (eg (6)), and strain-protected enzymatic collagen degradation (eg (11)). The premise is that these two mechanisms together are able to predict a transient and equilibrium responses of tissue adaptation to mechanical constraints. To evaluate this, they are captured in a numerical model and predictions are corroborated against distinct experimental observations. This abstract overviews the versatility of the model, using already presented (5) and new data.

Topics: Traction
Commentary by Dr. Valentin Fuster
2013;():V01AT02A004. doi:10.1115/SBC2013-14314.

Osteoarthritis (OA), commonly known as ‘wear and tear’ in human joints, affects over 27 million people in the United States [1]. There is currently no encompassing solution for the regeneration of damaged articular cartilage. One potential solution involves the close emulation of the native structure of articular cartilage, with special consideration given to maintaining the distinct organized zonal ultrastructure, characterized by both random and highly aligned zones of collagen fibrils, in order to preserve mechanical and cell signaling properties of the extracellular matrix [2]. Techniques such as electrospinning achieve high degrees of alignment, but do so at the cost of denaturing the collagen molecule [3] that may lead to inferior cell recognition and mechanical strength.

Commentary by Dr. Valentin Fuster
2013;():V01AT02A005. doi:10.1115/SBC2013-14361.

The molecules of the extracellular matrix in connective tissues are densely packed. Biofabrication methods to attain such molecular packing density are limited and electrochemical processing (EP) of monomeric collagen solutions is one of few means to attain molecular packing. During EP, the pH gradient between electrodes drives the electrophoretic mobility of collagen molecules toward the isoelectric point where molecules are compacted. Our earlier work used linear electrodes to fabricate highly aligned crosslinked collagen fibers for tendon tissue engineering [1–4]. Prior work compared electrocompacted-aligned matrices with uncompacted randomly oriented ones. Therefore, the effects of alignment and compaction were compounded in terms of assessing cell response. So as to take the matrix alignment variable out of the picture to investigate matrix compaction effects only, we employed disc shaped electrodes to obtain electrocompacted sheets which lack matrix alignment. The current study investigated: a) the degree of compaction, b) effect of compaction on the mechanical properties of the sheets, and, c) mesenchymal stem cell (MSC) proliferation and morphology on compacted sheets relative to uncompacted collagen gels.

Commentary by Dr. Valentin Fuster
2013;():V01AT02A006. doi:10.1115/SBC2013-14518.

Cell sourcing for tissue engineered approaches to vascular repair is a serious issue confronting the field of cardiovascular tissue engineering. Omental mesothelium is a promising autologous cell source for vascular repair and has been used for numerous other therapies [1]. Until recently, omental mesothelium was only thought to play a paracrine role in wound healing but there is increasing evidence that omental mesothelium can undergo divergent terminal differentiation to reparative vasculogenic cell types including: endothelial cells, fibroblasts, or vascular smooth muscle cells.

Commentary by Dr. Valentin Fuster
2013;():V01AT02A007. doi:10.1115/SBC2013-14851.

A multi degree of freedom skeletal muscle system stimulated via optical control is presented. These millimeter-scale, optically excitable 3D skeletal muscle bio-actuators are created by culturing genetically modified precursory muscle cells that are activated with light: optogenetics. These muscle bio-actuators are networked together to create a distributed muscle system. Muscle systems can manipulate loads having no fixed joint. These types of loads include shoulders, the mouth, and the jaw.

Topics: Actuators , Muscle
Commentary by Dr. Valentin Fuster


2013;():V01AT03A001. doi:10.1115/SBC2013-14014.

Atherosclerosis is a disorder of the arterial wall. The vessel wall is invaded by lipids and inflammatory cells which can lead to thickening of the arterial wall and eventually to formation of a vulnerable atherosclerotic plaque. Such a vulnerable plaque consists of intraplaque hemorrhage, inflammatory cells, a lipid rich necrotic core (LRNC) and a thin fibrous cap separating the thrombogenic LRNC from the blood stream. The thin fibrous cap is prone to rupture, which can cause thrombus formation and subsequent embolization of thrombus into distal vessels or acute occlusion. This is the major cause of stroke and myocardial infarction.

Commentary by Dr. Valentin Fuster
2013;():V01AT03A002. doi:10.1115/SBC2013-14313.

Coronary atherosclerotic plaques are frequently focal lesions that have variable rates of progression. Wall shear stresses (WSS) create a number of responses in endothelial cells that can lead to the localization and progression of these lesions, and in vivo coronary segments with low WSS have been found to develop greater plaque progression than segments of higher WSS.

Commentary by Dr. Valentin Fuster
2013;():V01AT03A003. doi:10.1115/SBC2013-14466.

The complex hemodynamics observed in the human aorta make this district a site of election for an in depth investigation of the relationship between fluid structures, transport and pathophysiology. In recent years, the coupling of imaging techniques and computational fluid dynamics (CFD) has been applied to study aortic hemodynamics, because of the possibility to obtain highly resolved blood flow patterns in more and more realistic and fully personalized flow simulations [1]. However, the combination of imaging techniques and computational methods requires some assumptions that might influence the predicted hemodynamic scenario. Thus, computational modeling requires experimental cross-validation. Recently, 4D phase contrast MRI (PCMRI) has been applied in vivo and in vitro to access the velocity field in aorta [2] and to validate numerical results [3]. However, PCMRI usually requires long acquisition times and suffers from low spatial and temporal resolution and a low signal-to-noise ratio. Anemometric techniques have been also applied for in vitro characterization of the fluid dynamics in aortic phantoms. Among them, 3D Particle Tracking Velocimetry (PTV), an optical technique based on imaging of flow tracers successfully used to obtain Lagrangian velocity fields in a wide range of complex and turbulent flows [4], has been very recently applied to characterize fluid structures in the ascending aorta [5].

Commentary by Dr. Valentin Fuster
2013;():V01AT03A004. doi:10.1115/SBC2013-14708.

The use of realistic anatomic human carotid artery bifurcation (CB) models with a realistic blood waveform leads to physiologically relevant numerical simulations. To study the effects of head posture on the geometry and hemodynamics of the CB, Magnetic resonance imaging (MRI) was used on six healthy volunteers in two different head postures: 1) the supine neutral (N) and 2) the prone with rightward head rotation (P) up to 80°. Geometric differences with posture change in both the left (LCA) and right (RCA) carotid arteries were reported before [1]. The blood velocity waveform for each individual was obtained using phase-contrast MRI (PCMRI) at five diameters upstream of CB. Results have shown that peak systolic blood flow rate is reduced, in the prone position for both RCA and LCA in all six volunteers. To investigate the effects of the reduced peak systolic flow on the hemodynamics of the CB, numerical simulations were performed for a volunteer that exhibited the most geometric changes for the prone position in comparison to the other five based on specific geometric parameters [1, 2]. For the two investigated head postures the observed measured input waveforms were used.

Commentary by Dr. Valentin Fuster
2013;():V01AT03A005. doi:10.1115/SBC2013-14726.

Atherosclerosis is a cardiovascular disease characterized by plaque formation in the vessel wall. Plaque rupture initiates thrombus formation and may lead to myocardial infarction, stroke and eventually, to sudden death [1]. A plaque ruptures when the mechanical stress in the plaque exceeds its strength. Thus, biomechanical models have a great potential to predict plaque rupture. For reliable prediction models, correct material properties of plaque components at large strains are prerequisite. However, the data available in literature are limited and show a wide range.

Commentary by Dr. Valentin Fuster
2013;():V01AT03A006. doi:10.1115/SBC2013-14825.

Mechanical circulatory support (MCS) devices, such as the total artificial heart and ventricular assist devices, are employed as bridge-to-transplant or destination therapies for advanced heart failure.[1] Recipients of these life-saving MCS devices have to endure life-long antiplatelet regimens to counteract thromboembolic events resulting from exposure of platelets to high shear stress. Often, large animal models, i.e. bovine and ovine, have been utilized to evaluate the performance and blood compatibility of these cardiovascular devices. Therefore, understanding and correlating the interspecies differences of platelet reactivity is crucial in optimizing the design of MCS devices.

Commentary by Dr. Valentin Fuster

Atherosclerosis: Aneurysms and Heart Valves Posters

2013;():V01AT04A001. doi:10.1115/SBC2013-14079.

With a prevalence of 1.3 million cases in the United States, the bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific aortic valve disease (CAVD) [1]. The most prevalent type-I morphology, which results from left-/right-coronary cusp fusion, generates different hemodynamics than a tricuspid aortic valve (TAV). While valvular calcification has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors [2–3]. In particular, the wall shear stress (WSS) produced by blood flow on the leaflets regulates homeostasis in the TAV. In contrast, WSS alterations cause valve dysfunction and disease [4]. While such observations support the existence of synergies between valvular hemodynamics and biology, the role played by BAV WSS in valvular calcification remains unknown. The objective of this study was to isolate the acute effects of native BAV WSS abnormalities on CAVD pathogenesis.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A002. doi:10.1115/SBC2013-14113.

We present a quantified description of the fluid flow and a novel flowline-based meshing technique to create adaptive grids for Computational Fluid Dynamics (CFD) simulations in patient-specific intracranial aneurysms. The adaptive grid density is obtained such that it captures the fine geometrical details of the flow with high grid density, while smoother flow characteristics are calculated with a coarser grid density. The correlation between the topological characteristics of the flow and the element size of the adaptive grid results in a practical mathematical formula for calculating the element size using only one uniform base mesh and a user defined implementation in CFD post processors.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A003. doi:10.1115/SBC2013-14192.

Rupture of aneurysms is a leading cause of death in the United States. Extensive biomechanical studies have shown that mechanical stress in aneurysm walls plays a critical role in the rupture of aneurysms. Highly elevated local stress and degraded aneurismal walls are believed to make aneurysms vulnerable to rupture [1–3]. Asymmetric aneurysms with irregular shape and wall thickness are vulnerable to rupture. Aneurismal arteries are often tortuous such as in the Loeys-Dietz syndrome [4], but the mechanism is unclear.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A004. doi:10.1115/SBC2013-14234.

Tissue engineering represents a promising technique to overcome the limitations of the current valve prostheses, since it allows for synthesizing living, autologous valves that have the potential to grow and remodel in response to changing demands. However, one particular problem with tissue-engineered heart valves (TEHVs) is retraction of the valve leaflets (Fig. 1), which results in valvular insufficiency [1, 2]. As long-term regurgitation will lead to ventricular failure, this is a critical problem that needs to be solved before TEHVs can be used in clinical practice.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A005. doi:10.1115/SBC2013-14240.

According to the Dorland Medical Dictionary a cerebral aneurysm is an abnormal bulge or ballooning in a blood vessel supplying the brain. Aneurysms can rupture and bleed into the area between the brain and the surrounding membrane. A noticeable percentage of the human population, typically 2 to 5% depending on the country, harbors a cerebral aneurysm, but only about 0.1% of those aneurysms rupture annually [1].

Commentary by Dr. Valentin Fuster
2013;():V01AT04A006. doi:10.1115/SBC2013-14265.

Splines are the standard tools in computer aided design for geometric representations and have been recently integrated into the finite element analysis of structures and fluids [1]. As the biomedical engineering is making progress, there is a need for an integrated tool for expanding the geometrical representation to include the microstructural details specific to soft tissue, e.g. fiber alignment, orientation, crimp and stiffness. In this work, a spline-based method is presented for aortic valves which facilitates mapping of the fiber structure from any aortic valve specimen to any other aortic valve geometry through a common parameter space. This techniques also has the ability to calculate mean tissue microstructure of representative population. Also strain and pre-strain from in-vivo state to the in-vitro state, where all the mechanical tests are done, are calculated for forward and inverse modeling of aortic valves.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A007. doi:10.1115/SBC2013-14289.

The number of numerical studies predicting blood flow in intracranial aneurysms is rapidly increasing over the last years. Due to a high spatial as well as temporal resolution, computational fluid dynamics (CFD) approaches offer a high potential to investigate flow interaction within the human vascular system. However, state-of-the-art methods still underlie several assumptions, e.g., rigid vessel walls, analytical boundary conditions or the consideration of blood as a single-phase continuous fluid. In consequence, the acceptance of CFD is still limited among a majority of physicians [1]. In order to overcome these reasonable doubts, simulations need to be validated via experiments. Therefore, two patient-specific intracranial aneurysms were measured by means of 7-Tesla magnetic resonance imaging (MRI). Afterwards, highly resolved numerical simulations were carried out and the peak-systolic velocity fields compared in a qualitative manner.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A008. doi:10.1115/SBC2013-14297.

Treatment of rupture-prone carotid atherosclerotic plaques, by means of endarterectomy, is only beneficial for patients with unstable plaques, which comprise only 16% of the patient population [1]. It is therefore of great interest to assess morphology, geometry and mechanical deformation of the plaque and its components, to prevent unnecessary treatment. However, due to the complex geometry of stenotic arteries, 3D information at both high temporal and spatial resolution is required. Besides, assessment of plaque morphology in vivo can still not be routinely performed. Therefore, one has to rely on in vitro methods to obtain morphology and mechanical properties, and thus rupture risk.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A009. doi:10.1115/SBC2013-14335.

Calcific aortic valve disease affects a wide range of the population in the United States. Each year there are approximately 50,000 valve replacements due to this disease [(Freeman & Otto, 2005)]. While it is unclear what the exact causes of CAVD are, it does appear to be correlated to local hemodynamic conditions particularly related to the complex spatio-temporal nature of fluid wall shear stress dynamics that the aortic side of the leaflets experience.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A010. doi:10.1115/SBC2013-14374.

Cerebral aneurysms are known as the top reason of subarachnoid hemorrhage (SAH). They are studied in the medical and the engineering field to reveal their pathogenesis, progression, and rupture mechanisms1,2. The pathological studies revealed the site of predilection, rupture rate, the risk factors1, inflammation within the aneurysm, and conditions of endothelial cells (EC) in the aneurysms3. The current pathological analyses of the cerebral aneurysms are all phenomenological and it does not consider the cause-and-effect mechanisms between the mechanical stimulation and the physiological effect although hemodynamics is thought to play an important role in the mechanisms of aneurysms. One reason that the aneurysms’ mechanisms remain unsolved is because the pathology and hemodynamics are studied independently. Purpose of this study is to reveal the relationship of endothelial cell, thickness, and hemodynamics of the cerebral aneurysms by comparing the scanning electron microscope (SEM) analyses, μCT, and the computational fluid dynamics (CFD) analyses of the cerebral aneurysms.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A011. doi:10.1115/SBC2013-14402.

As endothelial cells (ECs) age, morphological and physiological changes occur that may alter macromolecular transport and cause subsequent disease development. ECs in atherosclerotic regions exhibit high cell turnover and high levels of oxidative stress due to transient flow patterns and low and oscillating shear stress. This leads to replicative or stress-induced senescence. Resveratrol indirectly reverses senescence-associated phenotypes via competitive inhibition of cAMP-degrading phosphodiesterases (PDEs). Elevated levels of membrane-associated cAMP activate the cyclic AMP-regulated guanosine nucleotide exchange factor Epac1 which, in turn, leads to guanosine triphosphate (GTP) binding to the small G protein Rap1. GTP bound Rap1 activates the deacetylase SIRTUIN1 (SIRT1) but also causes changes to the cortical cytoskeleton and organization of VE-cadherin mechanosensor in the endothelial junctions (Figure 1).

Commentary by Dr. Valentin Fuster
2013;():V01AT04A012. doi:10.1115/SBC2013-14413.

Aneurysm dissection and rupture, resulting in imminent death, is the primary risk associated with thoracic aortic aneurysms (TAA). Nearly 60% of TAA involves the ascending aorta [1]. Dissection and rupture occur when the remodeled tissue is no longer able to withstand the stresses generated by the arterial pressure. As the ascending TAA grows, however, changes in its mechanical behavior, particularly wall strength, are unknown.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A013. doi:10.1115/SBC2013-14424.

In 2008 the overall rate of death attributable to cardiovascular disease, or CVD, is 244.8 per 100,000. On the basis of these mortality rate data, one American dies due to CVD on an average of every 39 seconds. Of these deaths, abdominal aortic aneurysm (AAA) accounts for 11,079 [1]. Although an estimate of the total economic burden of AAA is not available, the average cost per discharge for a ruptured AAA exceeded $93,000 in 2003 [2]. Generally, an abdominal aortic aneurysm (AAA) is an irreversible focal dilation of an artery to 1.5 times its normal diameter [3]. AAAs are characterized by the destruction of elastin and collagen in the media and adventitia, smooth muscle cell loss with thinning of the medial wall, infiltration of lymphocytes and macrophages, and neovascularization [4, 5].

Commentary by Dr. Valentin Fuster
2013;():V01AT04A014. doi:10.1115/SBC2013-14465.

Mitral valve (MV) disease is the most prevalent form of heart valve disease among the US population [1]. MV disease can affect any one of the four components of the mitral valve: chordae tendinae, valve leaflets, papillary muscles or the supporting annulus. In one example of MV disease the annulus can become dilated, and this can subsequently lead to mitral valve insufficiency. Various surgical and catheter based techniques have been developed for repair or replacement of a dysfunctional MV, and many of these procedures involve suturing or anchoring devices directly to the annulus, thus restricting further dilatation of the annulus.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A015. doi:10.1115/SBC2013-14471.

Atherosclerotic plaque progression is believed to be associated with low and oscillating flow shear stress conditions [1–3]. In vivo image-based coronary plaque modeling papers are relatively rare because clinical recognition of vulnerable coronary plaques has remained challenging [3–4]. Samady et al. [3] published their seminal patient follow-up coronary plaque progression study and indicated that flow shear stress (FSS) was associated with plaque progression and remodeling. We have published results based on follow-up studies showing that advanced carotid plaque had positive correlation with flow shear stress and negative correlation with plaque wall stress (PWS) [4]. In this paper, patient-specific intravascular ultrasound (IVUS)-based coronary plaque models with fluid-structure interaction (FSI), on-site pressure and ex vivo biaxial mechanical testing of human coronary plaque material properties were constructed to obtain flow shear stress and plaque wall stress data from six patients to investigate possible associations between vessel wall thickness and both flow shear stress and plaque wall stress conditions.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A016. doi:10.1115/SBC2013-14475.

Coronary artery disease and peripheral artery disease remain a significant source of mortality and vascular morbidity in the United States; both affecting over 14 million Americans.[1] Although a number of both open and endovascular procedures are available for treating occlusive lesions, post-procedure intimal hyperplasia (IH) and pathological wall adaptation in treated arteries cause further need for treatment. As on average 50% of patients receiving these treatments must receive further vascular intervention to prevent the continued expansion of IH into the vessel lumen, there is a need to improve our understanding of the underlying causes of IH formation.[2]

Topics: Diseases
Commentary by Dr. Valentin Fuster
2013;():V01AT04A017. doi:10.1115/SBC2013-14501.

Atherosclerotic plaque rupture is the primary cause of cardiovascular clinical events such as heart attack and stroke. It is commonly believed that plaque rupture may be linked to critical mechanical conditions. Image-based computational models of vulnerable plaques have been introduced seeking critical mechanical indicators which may be used to identify potential sites of rupture [1–5]. A recent study by Tang et al. [4] using in vivo MRI-based 3D fluid-structure interaction (FSI) models for human carotid plaques with and without rupture reported that higher critical plaque wall stress (CPWS) values were associated with plaques with rupture, compared to those without rupture. However, existing computational plaque models are mostly for carotid plaques based on MRI data. Comparable similar studies for coronary plaques are lacking in the current literature. In this study, 3D computational multi-component models with FSI were constructed to identified 3D critical plaque wall stress, critical flow shear stress (CFSS) based on ex vivo MRI data of coronary plaques acquired from 10 patients. The patients were split into 2 groups: patients died in carotid artery disease (CAD, Group 1, 6 patients) and non CAD (Group 2, 4 patients). The possible link between CPWS and death in CAD was investigated by comparing the CPWS values from the two groups.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A018. doi:10.1115/SBC2013-14580.

The rupture of a cerebral aneurysm can have devastating effects, with approximately 50% of patients dying within one month of rupture [1]. Aneurysms of the basilar artery are among the most prevalent of posterior circulation cerebral aneurysms [2]. Although the exact mechanisms behind their formation, growth and rupture are unknown, it is believed that hemodynamics plays an important role [3].

Topics: Blood , Modeling , Aneurysms
Commentary by Dr. Valentin Fuster
2013;():V01AT04A019. doi:10.1115/SBC2013-14603.

Despite half a century of use, mechanical heart valves still require further research to reduce the non-physiologic nature of the flow field, which is the source of potential medical complications, of which the most serious complication is thrombus formation [1]. In the systolic phase of the flow, excessive fluid stresses are generated by the non-physiologic flow patterns [2, 3]. In the closed valve position, a large pressure gradient is imposed across the device which leads to the generation of strong and damaging small-scale leakage flows that entrain platelets such that they are exposed to elevated stresses for excessive time durations [4–6].

Commentary by Dr. Valentin Fuster
2013;():V01AT04A020. doi:10.1115/SBC2013-14633.

Advanced analyses of soft biological tissues have shown substantial subject-specific variability in mechanical properties [1]. Such variability is also easily observed at a geometrical or morphological level, and has been reported also in mechanical tests on biological tissue samples [1, 2]. While there is wide interest in reproducing accurate geometries for subject-specific modeling, constitutive parameters for mechanical models often use averaged data from mechanical tests [3]. Outliers are typically neglected, and only the ‘mean’ tissue behavior is considered. However, due to an increased interest in using multi-scale and finite element (FE) models for medical device testing and surgical planning [4], understanding of the variability of the outlier tests becomes increasingly important. In particular, by using detailed mechanistic constitutive models, it might be possible to classify the different mechanical behaviors observed on the basis of the changes in the constitutive parameters. This process could lead to the definition of a library of different ‘healthy’ or ‘diseased’ constitutive parameters to be used in computational analyses.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A021. doi:10.1115/SBC2013-14693.

Atherosclerosis is a cardiovascular disease that occurs within the walls of arteries and can result in a reduction of the lumen diameter. This reduction can cause a decrease in blood flow to the brain which can lead to a stroke event. Carotid angioplasty stenting (CAS) is a minimally invasive surgical treatment for stroke prevention and has been found to show equivalency to the highly invasive open artery repair which is a more commonly used surgical technique (Brott et al. 2010). Development in the design of stent and angioplasty devices is necessary for the continuous improvement of minimally invasive treatments of carotid artery disease. However, a major concern with regard to this treatment is the rupture of the plaque due to the almost instantaneous inflation of the stent device. To further improve the design of these devices a better understanding of the mechanical behaviour and failure of the plaque during minimally invasive treatment in the circumferential direction is required. A limited amount of data exists regarding the mechanical behaviour of atherosclerotic plaques under physiological conditions. Studies undertaken by Maher et al. (2009) and Teng et al. (2009) have tested the tensile properties of the plaque in the circumferential direction but these studies employed unphysiological strain rates which limit the true representation of the global properties of the plaque. This current study aims to biologically and mechanically characterise the whole plaque tissue and to determine if a correlation exists between the mechanical behaviour and the pre-operatively identified biological content of the plaque.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A022. doi:10.1115/SBC2013-14730.

Abdominal aortic aneurysm (AAA) represents an asymptomatic cardiovascular type of disease, that is diagnosed in elder people over 60 years old. It is characterised by a ballooning of the abdominal aorta, which grows, at different rates in different patients. If left untreated, it will rupture causing severe internal bleeding, which can lead to shock or death [1]. Medical devices such as bifurcated stent grafts (SG) are used for the treatment of this disease. To help improve SG performance, biomedical engineers design benchtop models for testing.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A023. doi:10.1115/SBC2013-14733.

Microscale mechanical properties of soft biomaterials, such as heart valves, are of interest to researchers studying the effects of matrix mechanical properties on cell function. Measurements at the microscale, on the order of 1–500 μm, are representative of the mechanical properties experienced by the cells in their environment (1). In contrast, other methods like conventional tensile/compression testing and atomic force microscopy provide macroscale and nanoscale properties, respectively, that do not reflect the local micromechanical environment at the cellular scale.

Topics: Biomaterials , Valves
Commentary by Dr. Valentin Fuster
2013;():V01AT04A024. doi:10.1115/SBC2013-14738.

Suturing a prosthetic ring to the mitral valve is one of the main challenges in percutaneous mitral valve annuloplasty. Novel self-anchoring fasteners developed for minimally invasive surgery may easily tear the tissue and cause their failure. Identification of the fracture toughness of the mitral valve tissue is an important step towards the optimization of these novel fasteners to minimize their deleterious effects on the surrounding tissue. Moreover, the study of rupture mechanism of the heart valve tissue can provide interesting information on the developing process of congenital mitral regurgitation due to the cleft mitral valve.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A025. doi:10.1115/SBC2013-14744.

Since the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus-1 (HIV-1) are living longer lives. However, HIV-1-positive (HIV-1+) patients are now experiencing many non-AIDS related comorbidities including myocardial infarction, atherosclerotic lesions, and other preclinical markers of atherosclerosis including increased carotid intima-media thickness (cIMT), arterial stiffness, and impaired flow-mediated dilation (FMD). Studies have implicated the virus, the treatment, or both in the progression of these co-morbidities, causing the exact mechanisms of cardiovascular disease progression to remain unclear.

Topics: Thickness
Commentary by Dr. Valentin Fuster
2013;():V01AT04A026. doi:10.1115/SBC2013-14749.

Aging and some pathologies such as arterial hypertension, diabetes, hyperglycemia, and hyperinsulimenia cause some geometrical and mechanical changes in the aortic valve microstructure. Cupsal thickening and lost of extensibility (increasing stiffness) are the consequences of these changes in the aortic valve which have a negative impact on the function of the valve [1]. The most frequent form of diseases of the aortic valve is the calcific aortic stenosis which is responsible for 80% of the North American deaths due to valvular heart diseases [2]. In this pathology, calcified nodules on the valve leaflets occur which lead to the thickening and stiffening of the leaflets and restricting the natural motion of the valve which presents an increased resistance to forward blood flow during the ejection phase of the cardiac cycle. To reduce the mortality and morbidity from the aortic stenosis, clinical management and proper diagnosis are essential [3]. Tranvalvular pressure gradient (TPG) and the effective orifice area (EOA), the minimum cross sectional area of the blood flow across the stenosis, are the most commonly used indices for assessing the aortic stenosis [4]. Numerous studies have been done to relate the TPG across the stenosis to the blood flow rate and EOA. Gorlin (1951) was the first to establish a relationship between TPG and EOA [5]. Several studies have reported deviations in valve area calculation by using Gorlin formula. This formula was derived based on some assumptions such as rigid circular orifice, non viscous and steady flow, while valvular orifices are compliant and the flow through them is viscous and pulsatile [6]. Several corrections have been proposed. However, even with these improved formula, significant deviations are still reported [7]. Calark (1978), Bermejo et al (2002) and Garcia et al (2006), by presenting a theoretical model, tried to express TPG in terms of the blood flow rate and EOA [8–10]. None of these studies considered the effect of the aortic root compliance on TPG. Nobari et al reported that the stiffening of the aorta changes the pressure drop and affects the leaflets motion [11]. Therefore, the objective of this study is to develop a 1D model for assessing the aortic pressure drop for the transient viscous blood flow across the aortic stenosis, by taking into account the vessel wall compliance. The derived TPG will be expressed in terms of the surrogate variables which are anatomical and hemodynamic data meaningful and accessible for physicians.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A027. doi:10.1115/SBC2013-14758.

Annulus dilation is one of the main causes of functional mitral regurgitation. Although the annulus dilation is usually accompanied by left ventricle dilation and dysfunction, the mechanical relation between them is not fully elucidated yet. In this paper, the assumption is made that the ventricular dysfunction increases the cyclic loading conditions on the mitral valve apparatus. This effect may cause fatigue and weaken the tissue. This hypothesis is investigated in vitro by applying increased cyclic loadings to the tissue and evaluating the tissue stiffness during the cycles. The results of this study show that the tissue loses its strength after cyclic fatigue loadings.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A028. doi:10.1115/SBC2013-14770.

Neurointerventionists are routinely faced with the dilemma whether or not to treat unruptured intracranial aneurysms. Hemodynamic and morphological characteristics have become important considerations for aneurysm rupture-risk assessment [1]. Clinicians require an integrated tool that analyzes these parameters to help make treatment decisions in clinical workflow, however such a tool does not exist. To this end, Toshiba Stroke and Vascular Research Center (TSVRC) at University at Buffalo and Orobix Srl (Italy) have developed a prototype of a computational workflow system. Termed AView, it is an integrated, image-based vascular analysis tool for rapid assessment of aneurysmal hemodynamics, morphometrics, rupture risk assessment, and treatment planning.

Commentary by Dr. Valentin Fuster
2013;():V01AT04A029. doi:10.1115/SBC2013-14771.

The aortic and pulmonary semilunar heart valve leaflets (AV and PV respectively) are heterogeneous structures comprised of three distinct tissue layers. All three layers contain varying amounts of collagen, elastin and glycosaminoglycans (GAGs). The fibrosa layer is an undulated structure that faces the aorta comprised primarily of Type 1 collagen highly aligned in the circumferential direction. On the opposite face of the valve is the ventricularis layer that is populated with an organized elastin network. The spongiosa layer resides between the fibrosa and ventricularis and is rich in GAGs. All three layers work in unison at the tissue level to produce effective leaflet mechanical behavior. While the mechanical behavior of the fibrosa and ventricularis layers have been well studied [1], little information exists on the effective mechanical behavior of the GAG rich spongiosa layer.

Commentary by Dr. Valentin Fuster

BioFluid Mechanics Posters

2013;():V01AT05A001. doi:10.1115/SBC2013-14019.

The airway binary fluid layer and the structural characteristics of the upper airways have significant influence on the activity of the airway muscles by changing airway compliance and collapsibility during obstructive sleep apnea trauma. The uvula plays an important role in the collapse process. Using MRI scans, this paper develops a structural model for the uvula and determines its dynamic characteristics in terms of natural frequencies and mode shapes as a preliminary process to determine optimum conditions to therapeutically relieve upper airway obstruction. The effect of the variation of tissue elasticity due to water content is elaborated on.

Commentary by Dr. Valentin Fuster
2013;():V01AT05A002. doi:10.1115/SBC2013-14025.

This paper investigates the effect of superimposed length oscillation (SILO) on tidal breathing on contracted airway smooth muscle (ASM) relaxation. The combined effect of SILO with each one of four inhibitors (Isoproterenol, Indomethacin, PD0980590 and SB 203580) is investigated to explore the molecular pathways involved in the tissue relaxation process.

Commentary by Dr. Valentin Fuster
2013;():V01AT05A003. doi:10.1115/SBC2013-14088.

Mechanical circulatory support (MCS) devices, which include ventricular assist devices (VADs), offer an attractive solution to approximately 35,000 end-stage heart failure patients eligible for transplants, of which only 2,000–2,300 are performed annually [1]. These devices are employed to augment the function of the ailing left and/or right ventricle and serve as bridge-to-transplant or destination therapy, but are often accompanied by thrombotic complications. Pathologic flow patterns are characteristic of VADs and increase susceptibility to shear-induced platelet activation, which leads to thrombus formation [2]. Patients implanted with such devices are routinely prescribed antiplatelets to tackle these complications. Despite this concurrent therapy, thromboembolic incident rates of 0.9–13% are reported for the widely-implanted Thoratec HeartMate II and MicroMed DeBakey VADs [3, 4]. This has spurred the development of design optimization techniques to lower or eliminate the incidence of thrombosis and reduce the dependence on pharmacotherapy management.

Commentary by Dr. Valentin Fuster
2013;():V01AT05A004. doi:10.1115/SBC2013-14116.

Coating vaginal or rectal epithelium using microbicidal gels is a promising preventive procedure against HIV and other sexually transmitted infections (STIs). A microbicidal gel is deployed as a delivery vehicle of anti-HIV and other anti-STI agents and it is also used to act as barrier between the pathogens and the biological tissue. The efficacy of a microbicidal gel depends greatly on the extent of the spreading and the amount of the epithelial surfaces covered.

Commentary by Dr. Valentin Fuster
2013;():V01AT05A005. doi:10.1115/SBC2013-14127.

During the delivery of a fetus, an obstetrician assists by applying gentle axial downward traction on the head until the shoulders clear the pubic bone followed by catching and supporting the delivered infant body. If the shoulders become lodged behind the maternal pelvis (shoulder dystocia), the physician may be required to perform additional maneuvers to free the shoulders (1,2). Of significant concern is the potential for injury of the fetus during this process. It is believed that hyperextension, misalignment of forces on the head, or excessive applied forces can result in injuries to the brachial plexus nerves running through the neck and shoulder resulting in temporary or permanent Erb’s of Klumpke’s palsies for the infant. It is important to recognize there are delivery forces that originate with uterine contractions and maternal val salvo. To better understand the forces exerted during delivery in order to prevent these injuries, our long-term research goal is to create a tool that can accurately quantify these forces to improve understanding of them and to create training tools for medical trainees. The research goal of this project was to examine what hand pressures are typical during this traction phase in a normal delivery and where they are applied on the hand of the obstetrician. A secondary research question was whether there are any differences between fully trained obstetricians and residents in these pressures.

Commentary by Dr. Valentin Fuster
2013;():V01AT05A006. doi:10.1115/SBC2013-14162.

The Circle of Willis (CoW) is a ring like structure located at the base of brain, which is composed of a single anterior communicating artery (ACoA), paired anterior cerebral arteries (ACAs), paired internal carotid arteries (ICAs), paired posterior communicating arteries (PCoAs), paired posterior cerebral arteries (PCAs), paired vertebral arteries (VAs) and a single basilar artery (BA). It is the main cerebral blood perfusion pathway and provides an important collateral channel in patients with severe carotid or vertebral artery disease. Over 50% of stroke cases are related to the stenosis of arteries in the CoW, so the detailed information of the cerebral hemodynamics under different pathology situations is important for a variety of clinical applications. Numerous experimental studies have been performed on this field from different perspectives, include the mechanism of stenosis in the CoW [1], risk assessment of cerebral aneurysm [2] and the impact of pathological variations on the flow distribution [3]. However, none of these researches focus on the influence of ICA stenosis rates on cerebral perfusion and the specific collateral mechanism of the Circle of Willis under such situations. In this paper, an experimental study on cerebral blood perfusion and the collateral mechanism under a series of ICA stenosis rates was carried out.

Topics: Hemodynamics