Rudolph L Gleason

• Ph.D.
• Professor at Georgia Institute of Technology

Objective False lumen expansion is a major factor that determines long-term survival of uncomplicated type B aortic dissection (TBAD). The objective of this study was to investigate whether structural wall stress distributions computed from patient-specific acute TBAD geometries can be used to predict aortic growth rates. Methods Three-dimensional...

Soil-transmitted helminths (STHs) are parasitic worms that impact over 1.5 billion people globally. The Kato–Katz technique analyzes stool samples for STHs, allowing for individual diagnoses of STH infection and the estimation of community-level prevalence. One challenge that arises with the procedure is that lab technicians often struggle to prepa...

Background: Type B aortic dissections (TBAD) develop from a tear in the intimal layer of the aorta, distal to the left subclavian artery. This tear separates the aorta into true (TL) and false lumens (FL), increasing the risk of dilation and rupture. In cases of surgical intervention, treatment for type B aortic dissections (TBAD) after the acute p...

Objective The outer false lumen wall (FLW) changes from thin/compliant to thick/rigid as aortic dissection transitions from the acute to chronic phase. This study investigates biomechanical stiffness and histological changes of the FLW as the dissected aorta ages. Methods The free outer FLW from human tissue was analyzed from chronic type B dissec...

Calcification has significant influence over cardiovascular diseases and interventions. Detailed characterization of calcification is thus desired for predictive modeling, but calcium deposits on cardiovascular structures are still often manually reconstructed for physics-driven simulations. This poses a major bottleneck for large-scale adoption of...

Non-rigid deformation of a template to fit 3D scans of human subjects is widely used to develop statistical models of 3D human shapes and poses. Complex optimization problems must be solved to use these models to parameterize scans of pregnant women, thus limiting their use in antenatal point-of-care tools in low-resource settings. Moreover, these...

Lymphedema is a condition in which lymph transport is compromised. The factors that govern the timing of lymphatic contractions are largely unknown; however, these factors likely play a central role in lymphatic health. Computational models have proven useful in quantifying changes in lymph transport; nevertheless, there is still much unknown regar...

Automated volumetric meshing of patient-specific heart geometry can help expedite various biomechanics studies, such as post-intervention stress estimation. Prior meshing techniques often neglect important modeling characteristics for successful downstream analyses, especially for thin structures like the valve leaflets. In this work, we present De...

Pulse wave velocity (PWV) is a key, independent risk factor for future cardiovascular events. The Moens-Korteweg equation describes the relation between PWV and the stiffness of arterial tissue with an assumption of isotopic linear elastic property of the arterial wall. However, the arterial tissue exhibits highly nonlinear and anisotropic mechanic...

The arterial stiffening is a strong independent predictor of cardiovascular risk and has been used to characterize the biological age of arteries ('arterial age'). Here we revealed that the Fbln5 gene knockout (Fbln5-/-) significantly increases the arterial stiffening for both male and female mice. We also showed that the arterial stiffening increa...

Background Peripheral arterial disease (PAD) is the 3rd leading type of atherosclerotic disease (ASD) morbidity. Arterial stiffness is intimately connected to the onset and progression of peripheral artery disease (PAD). The role of arterial stiffening on flow-mediated atherosclerotic plaque formation is not well understood. The objective of this s...

Abstract Preeclampsia–eclampsia syndrome is a leading cause of maternal mortality. The precise etiology of preeclampsia is still not well‐defined and different forms exist, including early and late forms or preeclampsia, which may arise via distinctly different mechanisms. Low‐dose aspirin administered at the end of the first trimester in women ide...

Introduction: Currently, Type B aortic dissection (TBAD) without the presence of either organ malperfusion or aortic rupture is managed with optimal medical therapy (OMT) consisting of an aggressive anti-hypertensive medical regimen and surveillance imaging. Although OMT achieves excellent early survival, the long-term outcomes with OMT alone remai...

Introduction: Type B Aortic Dissection (TBAD) is a lethal disease. The tissue mechanical property is of great importance for estimating TBAD rupture risk. This study sought to characterize the mechanical properties of stiffness and strength of dissection flap and adventitia tissues from patients with chronic TBAD. Methods: Aortic tissue removed fro...

Background Lymphedema is a condition in which the two primary functions of the lymphatic system, immunity and lymph transport, are compromised. Computational models of lymphatic function to characterize lymph transport have proved useful in quantifying changes in lymph transport in health and disease; however, much is unknown regarding the regulati...

Pulse wave velocity (PWV) is a key, independent risk factor for future cardiovascular events. The Moens-Korteweg equation describes the relation between PWV and the stiffness of arterial tissue with an assumption of isotopic linear elastic property of the arterial wall. However, the arterial tissue exhibits highly nonlinear and anisotropic mechanic...

Growth evolution laws, which mathematically describe how living tissues change their shape and properties in response to external stimuli, are required for modeling arterial growth. Traditionally, specific forms of growth laws are devised by domain experts. Since in vivo animal studies usually provide limited experimental data, generalization and i...

Cysteine cathepsins are potent proteases implicated in cardiovascular disease for degrading extracellular matrix (ECM) whose structure and integrity determine the mechanical behavior of arteries. Cathepsin knockout mouse models fed atherogenic diets have been used to study their roles in cardiovascular disease, but the impacts of cathepsin knockout...

CCN2 or connective tissue growth factor is up-regulated in response to disturbed flow and arterial stiffening. Carotid artery disease and peripheral arterial disease (PAD) are associated with disturbed flow and arterial stiffening. We have identified a key role for CCN2 in stiffened arterial remodeling and flow-mediated focal atherosclerotic plaque...

The maternal vasculature undergoes tremendous growth and remodeling (G&R) that enables a > 15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the mate...

Ascending aortic aneurysms (AsAA) often include the dilatation of sinotubular junction (STJ) and extend proximally into the aortic root, which usually leads to aortic insufficiency. The novel surgery of the V-shape resection of the noncoronary sinus, for treatment of AsAA with root ectasia, has been shown to be a simpler procedure compared to tradi...

Ascending aortic aneurysms (AsAA) often include the dilatation of sinotubular junction (STJ) which usually leads to aortic insufficiency. The novel surgery of the V-shape resection of the noncoronary sinus, for treatment of AsAA with root ectasia, has been shown to be a simpler procedure compared to traditional surgeries. Our previous study showed...

The lymphatic system transports lymph from the interstitial space back to the great veins via a series of orchestrated contractions of chains of lymphangions. Biomechanical models of lymph transport, validated with ex vivo or in vivo experimental results, have proved useful in revealing novel insight into lymphatic pumping; however, a need remains...

Contractile activity in the lymphatic vasculature is essential for maintaining fluid balance within organs and tissues. However, the mechanisms by which collecting lymphatics adapt to changes in fluid load and how these adaptations influence lymphatic contractile activity are unknown. Here we report a model of lymphatic injury based on the ligation...

Lymphatic contractions play a fundamental role in maintaining tissue and organ homeostasis. The lymphatic system relies on orchestrated contraction of collecting lymphatic vessels, via lymphatic muscle cells and one-way valves, to transport lymph from the interstitial space back to the great veins, against an adverse pressure gradient. Circumferent...

Objective: Sickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and...

Cephalopelvic disproportion (CPD)-related obstructed labour requires delivery via Caesarean section (C/S); however, in low-resource settings around the world, facilities with C/S capabilities are often far away. This paper reports three low-cost tools to assess the risk of CPD, well before labour, to provide adequate time for referral and planning...

Pelvic organ prolapse is characterized as the descent of the pelvic organs into the vaginal canal. In the USA, there is a 12% lifetime risk for requiring surgical intervention. Although vaginal childbirth is a well-established risk factor for prolapse, the underlying mechanisms are not fully understood. Decreased smooth muscle organization, composi...

Cephalopelvic disproportion (CPD)-related obstructed labor is accountable for 3–8% of the maternal deaths worldwide. The consequence of CPD-related obstructive labor in the absence of a Caesarian section (C/S) is often maternal or perinatal mortality or morbidity to the mother and/or the infant. Accurate and timely referral of at-risk mothers to he...

Raw data for all participants for eligibility criteria, anthropometry, clinical pelvimetry, radiological pelvimetry, and pregnancy outcomes. The columns in S1 Table correspond to the rows in this data collection form. This Table is provided in the supplemental file named “S2_Table.csv”. (CSV)

Data collection form used for ensuring the participants meet the eligibility criterion (Section 1) and recording anthropometric measurements (Section 2), clinical pelvimetry (Section 3), radiological pelvimetry (Section 4), and pregnancy outcomes (Section 5). The columns in S2 Table correspond to the rows in this data collection form. This Table is...

In vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1-/- mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1-/- and wild type (WT) mice were subjected to cecal ligation and puncture, a model of poly...

The intrinsic contraction of collecting lymphatic vessels serves as a pumping system to propel lymph against hydrostatic pressure gradients as it returns interstitial fluid to the venous circulation. We propose and validate that the maximum opposing outflow pressure along a chain of lymphangions at which flow can be achieved increases with the leng...

Background: Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial...

HIV- and highly active antiretroviral therapy (HAART)-associated elevations in oxidative stress likely play a role in incomplete immune reconstitution, opportunistic infections and non-AIDS co-morbidities. We aimed to test the hypothesis that children living with HIV exhibit elevated markers of oxidative stress and reduced antioxidant profiles and...

A primary purpose of the lymphatic system is to transport fluid from peripheral tissues to the central venous system in order to maintain tissue-fluid balance. Failure to perform this task results in lymphedema marked by swelling of the affected limb as well as geometric remodeling and reduced contractility of the affected lymphatic vessels. The me...

Ex vivo mechanical testing has provided tremendous insight towards prediction of the in-vivo mechanical behavior and local mechanical environment of the arterial wall; however, the role of perivascular support on the local mechanical behavior of arteries is not well understood. Here we present a novel approach to quantifying the impact of the periv...

Introduction: Arterial stiffness is an age related disease that doubles ones cardiovascular mortality and functions as an intermediary step in the formation of atherosclerosis. We have recently demonstrated that low and oscillatory wall shear stress, termed disturbed flow (d-flow), leads to arterial stiffness in otherwise normal arteries. Since d-f...

Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in p...

Activation of the nuclear hormone receptor, PPARγ, with pharmacological agonists promotes a contractile vascular smooth muscle cell phenotype and reduces oxidative stress and cell proliferation, particularly under pathological conditions including vascular injury, restenosis, and atherosclerosis. However, pharmacological agonists activate both PPAR...

Mechanical loading conditions are likely to play a key role in passive and active (contractile) behaviour of lymphatic vessels. The development of a microstructurally motivated model of lymphatic tissue is necessary for quantification of mechanically mediated maladaptive remodelling in the lymphatic vasculature. Towards this end, we performed cylin...

Background HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa. Methods Adult HIV-negative (n = 36), treatment naïv...

Residual deformations strongly influence the local biomechanical environment in a number of connective tissues. The sclera is known to be biomechanically important in healthy and diseased eyes, such as in glaucoma. Here, we study the residual deformations of the sclera, as well as the adjacent choroid and retina. Using freshly harvested porcine eye...

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactiv...

Major advances in highly active antiretroviral therapies (HAART) have extended the lives of people living with HIV, but there still remains an increased risk of death by cardiovascular diseases (CVD). HIV proteins have been shown to contribute to cardiovascular dysfunction with effects on the different cell types that comprise the arterial wall. In...

Quantifying arterial residual deformations is critical for understanding the stresses and strains within the arterial wall under physiological or pathophysiological loading conditions. This study presents novel findings on residual shear deformations in the left anterior descending coronary artery. Residual shear deformations were most evident when...

Objective: To explore the role of PPARγ in vascular regulation, smooth muscle VP16‐PPARγ‐overexpressing mice were subjected to studies of systemic vascular function, biomechanical testing, histological analysis, and molecular characterization. Methods: Mice with a flox‐controlled VP16‐PPARγ gene were crossed with mice containing a tamoxifen‐inducib...

The continuing lack of longitudinal histopathological and biomechanical data for human arteries in health and disease highlights the importance of studying the many genetic, pharmacological, and surgical models that are available in mice. As a result, there has been a significant increase in the number of reports on the biomechanics of murine arter...

Unique anatomic locations and physiologic functions predispose different arteries to varying mechanical responses and pathologies. However, the underlying causes of these mechanical differences are not well understood. The objective of this study was to first identify structural differences in the arterial matrix that would account for the mechanic...

On the basis of previous evidence that polymerase delta interacting protein 2 (Poldip2) increases NADPH oxidase 4 (Nox4) activity in vascular smooth muscle cells, we hypothesized that in vivo knockdown of Poldip2 would inhibit reactive oxygen species production and alter vascular function. Because homozygous Poldip2 deletion is lethal, Poldip2(+/-)...

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 atheros...

HIV positive patients on highly active antiretroviral therapy (HAART) have shown elevated incidence of a number of non-AIDS defining co-morbidities, including cardiovascular disease. Given that HAART regimens contain a combination of at least three drugs, that disease management often requires adjustment of these regimens, and HIV, independent of H...

Elastin fragmentation is a common characteristic of vascular diseases such as abdominal aortic aneurysms, peripheral arterial disease, and aortic dissection. Examining growth and remodeling in the presence of dysfunctional elastic fibers provides insight into the adaptive or maladaptive changes that tissues undergo in compensating for structural de...

HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease (CVD), including a higher risk of myocardial infarction and prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness (c-IMT), increas...

Changes in the local mechanical environment and tissue mechanical properties affect the biological activity of cells and play a key role in a variety of diseases, such as cancer, arthritis, nephropathy, and cardiovascular disease. Constitutive relations have long been used to predict the local mechanical environment within biological tissues and to...

Coronary and peripheral artery diseases are a leading cause of morbidity and mortality in developed countries. For severe cases, surgical intervention to bypass the disease using autologous vessels continues to be the preferred choice of treatment. These bypass vessels are typically obtained from the venous vasculature. Despite the superior long-te...

With over 33 million people infected with the human immunodefeciency virus (HIV-1), HIV-1 and autoimmune deficiency syndrome (AIDS) is a worldwide epidemic [1]. However, the development and widespread use of highly active antiretroviral therapy (HAART) has helped transform HIV-1 infection from a terminal disease leading to AIDS to a manageable chro...

Quantifying the mechanical behavior of very soft tissues (VST) is important when studying responses to injury or designing therapeutic devices; fat, brain, or liver being examples of such tissues. VST can have poor suture retention or clamp holding strength, making tensile tests difficult. As a result, uniaxial compression tests are typically the p...

Acquired immunodeficiency syndrome (AIDS) is considered a global epidemic with over 65 million people worldwide infected with the HIV-1 virus, the causative agent [1]. The development of highly active antiretroviral therapy (HAART) has significantly increased the life expectancy of people infected with the virus by slowing the progression to the de...

Vascular residual stress has been the subject of numerous studies for more than two decades. The importance of residual stress on vascular mechanics was first recognized by Chuong and Fung [1]. They demonstrated that when circumferential residual stress was considered in the mechanical analysis, a nearly uniform stress distribution was predicted ac...

Recent studies have revealed that carotid arteries from fibulin-5 (fbln5) null mice exhibit altered biomechanical and microstructural properties [1–2]. While the previous studies outline quantitative differences in mechanical properties of arteries from fbln5 null and wildtype mice, physical microstructural differences have yet to be quantified. Me...

The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstruc...

A structure-based mathematical model for the remodeling of arteries in response to sustained hypertension is proposed. The model is based on the concepts of volumetric growth and constitutive modeling of the arterial tissue within the framework of the constrained mixture theory. The major novel result of this study is that remodeling is associated...

Alteration in the mechanical properties of arteries occurs with aging and disease, and arterial stiffening is a key risk factor for subsequent cardiovascular events. Arterial stiffening is associated with the loss of functional elastic fibers and increased collagen content in the wall of large arteries. Arterial mechanical properties are controlled...

In contrast to the widely applied approach to model soft tissue remodeling employing the concept of volumetric growth, microstructurally motivated models are capable of capturing many of the underlying mechanisms of growth and remodeling; i.e., the production, removal, and remodeling of individual constituents at different rates and to different ex...

Understanding the mechanisms of cardiovascular disease progression is essential in developing novel therapies to combat this disease that contributes to 1 in 3 deaths in the United States every year. Endothelial dysfunction and its effects on vessel growth and remodeling are key factors in the progression and localization of atherosclerosis. Much o...

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

Along with insights into the potential for graft success, knowledge of biomechanical properties of small diameter tissue-engineered blood vessel (TEBV) will enable designers to tailor the vessels' mechanical response to closer resemble that of native tissue. Composed of two layers that closely mimic the native media and adventitia, a tissue-enginee...

Identification of an appropriate stress-free reference configuration is critically important in providing a reasonable prediction of the intramural stress distribution when performing biomechanical analyses on arteries. The stress-free state is commonly approximated as a radially cut ring that typically opens into a nearly circular sector, relievin...

Good predictions of the local mechanical environment of the tissue with known geometry and applied loads are fundamental to quantifying the biological response of tissues to mechanical stimuli. Whereas mean stresses in cylindrical sections of blood vessels may be calculated directly from measured loads and vessel geometry (e.g., Laplace's law), pre...

Mechanical stimulation has been shown to dramatically improve mechanical and functional properties of gel-derived tissue engineered blood vessels (TEBVs). Adjusting factors such as cell source, type of extracellular matrix, cross-linking, magnitude, frequency, and time course of mechanical stimuli (among many other factors) make interpretation of e...

To accomplish their physiological function, arteries have to remain patent under physiological loads, exhibit sufficient mechanical strength, and be capable of preserving their configuration with a sufficient reserve of safety. The latter requirement means that an artery has to be a mechanically stable structure. Among possible patterns of loss of...

Fibulin-5 is an extracellular matrix (ECM) protein that interacts with integrins and plays a critical role in organizing elastic fibers. Gross observation and histological examination reveal that carotid arteries from fibulin-5 knockout (fib5-/-) mice have disrupted elastic lamellae and are more tortuous [1]. The properties of fibulin-5 null mice p...

Vascular remodeling occurs as cells sense changes in their mechanical environment. Thus, quantifying the cells’ local environment in terms of stress and strain distributions is an important aspect in studies of vascular remodeling. Knowledge of the constitutive behavior of vessel will allow the local stresses and strains to be calculated given appl...

It is known that arteries adapt and remodel to changes in their loading conditions. Evolution of mechanical properties of blood vessels is associated with numerous chronic and acute conditions such as hypertension and coronary thrombosis. In addition, treatments such as bypass surgery create loading conditions not seen in normal arteries. Blood ves...

It is becoming evident that tissue-engineered constructs adapt to altered mechanical loading, and that specific combinations of multidirectional loads appear to have a synergistic effect on the remodeling. However, most studies of mechanical stimulation of engineered vascular tissue engineering employ only uniaxial stimulation. Here we present a no...

Arteries exhibit a remarkable ability to adapt to diverse genetic defects and sustained alterations in mechanical loading. For example, changes in blood flow induced wall shear stress tend to control arterial caliber and changes in blood pressure induced circumferential wall stress tend to control wall thickness. We submit, however, that the axial...

As patients with muscular dystrophy live longer because of improved clinical care, they will become increasingly susceptible to many of the cardiovascular diseases that affect the general population. There is, therefore, a pressing need to better understand both the biology and the mechanics of the arterial wall in these patients. In this paper, we...

There is a great unmet clinical need to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune response and suitable mechanical properties. In this paper we describe experimental and computational frameworks to characterize the use of mechanical stimuli to improve the mechanical properties of TEBVs. We mod...

There is a great unmet clinical need to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune response, suitable mechanical properties, and a capacity to remodel to their environment [2, 3]. Development of a clinically useful small diameter TEBV will surely rely on techniques from a wide variety of discip...

Muscular dystrophy is characterized by skeletal muscle weakness and wasting, but little is known about possible alterations to the vasculature. Many muscular dystrophies are caused by a defective dystrophin-glycoprotein complex (DGC), which plays an important role in mechanotransduction and maintenance of structural integrity in muscle cells. The D...

Vascular remodeling plays a key role in many physiological and pathophysiological processes, as well as the success or failure of many clinical interventions; examples include vascular development and aging, hypertension and atherosclerosis, and restenosis of vascular grafts. Despite the explosion of information on vascular remodeling, from the mol...

Recent advances in medical imaging, computational methods, and biomechanics promise to enable significant improvements in engineering-based decision making in vascular medicine, surgery, and training. To realize the potential of this approach, however, we must better synthesize the separate advances, particularly those in biofluid mechanics and art...

Many have studied the roles of altered blood flow and pressure on adaptive responses of blood vessels, but few have studied the role of altered axial loads. We exposed common carotid arteries from wild-type mice to low, medium, or high axial extensions while maintaining the same pressure and luminal flow rate for two days in culture, and studied ad...

As patients with muscular dystrophy live longer because of improved clinical care, they will become increasingly susceptible to many of the cardiovascular diseases that affect the general population. There is, therefore, a pressing need to better understand both the biology and the mechanics of the arterial wall in these patients. In this paper, we...