Robert Gorman
University of Pennsylvania, Surgery, Faculty Member
Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises... more
Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises when using in vivo images of the heart to generate the reference state of the model. An unloaded reference configuration is needed to accurately represent the deformation of the heart. However, it is rare for a beating heart to actually reach a zero-pressure state during the cardiac cycle. To overcome this, a computational technique was adapted to determine the unloaded configuration of an in vivo porcine left ventricle (LV). In the current study, in vivo measurements were acquired using magnetic resonance images (MRI) and synchronous pressure catheterization in the LV (N = 5). The overall goal was to quantify the effects of using early-diastolic filling as the reference configuration (common assumption used in modeling) versus using the unloaded refer...
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Residual and physiological functional strains in soft tissues are known to play an important role in modulating organ stress distributions. Yet, no known comprehensive information on residual strains exist, or non-invasive techniques to... more
Residual and physiological functional strains in soft tissues are known to play an important role in modulating organ stress distributions. Yet, no known comprehensive information on residual strains exist, or non-invasive techniques to quantify in-vivo deformations for the aortic valve (AV) leaflets. Herein we present a completely non-invasive approach for determining heterogeneous strains - both functional and residual - in semilunar valves and apply it to normal human AV leaflets. Transesophageal 3D echocardiographic (3DE) images of the AV were acquired from open-heart transplant patients, with each AV leaflet excised after heart explant and then imaged in a flattened configuration ex-vivo. Using an established spline parameterization of both 3DE segmentations and digitized ex-vivo images (Aggarwal et al., 2014), surface strains were calculated for deformation between the ex-vivo and three in-vivo configurations: fully open, just-coapted, and fully-loaded. Results indicated that ...
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Unlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated... more
Unlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression. Local wall shear stress was calculated from 4-dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midven...
The goal of this study was to investigate the sensitivity of computational models of the heart to their incorporated myofiber architecture during diastole. This architecture plays a critical role in the mechanical and electrical function... more
The goal of this study was to investigate the sensitivity of computational models of the heart to their incorporated myofiber architecture during diastole. This architecture plays a critical role in the mechanical and electrical function of the heart and changes after myocardial tissue remodeling, which is associated with some of the most common heart diseases. In this study, a left ventricular finite element model of the porcine heart was created using magnetic resonance imaging, which represents the in vivo geometry. Various myofiber architectures were assigned to the finite element mesh, in the form of fiber and sheet angles. A structural-based material law was used to model the behavior of passive myocardium and its parameters were estimated using measured in vivo strains and cavity volume from magnetic resonance imaging. The final results showed noticeable sensitivity of the stress distribution to both the fiber and sheet angle distributions. This implies that a structural-base...
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Chapter 28. Ischemic Mitral Regurgitation. Robert C. Gorman/ Joseph H. Gorman, III/ L. Henry Edmunds, Jr. ...
... N Engl J Med 1999;341:556-62. 3. Mohamed MK, Hussein MH, Massoud AA, et al. ... FATHIA GIBRIL, MD ROBERT T. JENSEN, MD National Institute of Diabetes and Digestive and Kidney Diseases Bethesda, MD 20892-1804 1. Metz DC, Jensen RT. ...
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Apoptosis induced mitochondrial destruction and dysfunction has been shown to play an important role in the pathogenesis of both acute cardiac ischemia-reperfusion injury and chronic myocardial infarction-induced ventricular remodeling.... more
Apoptosis induced mitochondrial destruction and dysfunction has been shown to play an important role in the pathogenesis of both acute cardiac ischemia-reperfusion injury and chronic myocardial infarction-induced ventricular remodeling. Unfortunately this understanding has not translated into effective therapeutic strategies for either condition-mostly due to an inability to assess mitochondrial dysfunction/apoptosis effectively in humans. All current measures of apoptosis are pseudo-quantitative
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ABSTRACT Although mitral valve (MV) repair initially restores normal leaflets coaptation and stops MV regurgitation, in long term it can also dramatically change the leaflet geometry and stress distribution that may be in part responsible... more
ABSTRACT Although mitral valve (MV) repair initially restores normal leaflets coaptation and stops MV regurgitation, in long term it can also dramatically change the leaflet geometry and stress distribution that may be in part responsible for limited repair durability. As shown for other collagenous tissues, such changes in geometry and loading reorganize the fiber architecture. In addition, MV interstitial cells respond to the altered stress by undergoing alterations in biosynthetic function, which would affect the load-bearing capabilities of MV and its long-term durability. Thus, investigating the repair-induced MV stress and the concomitant microstructural alterations is a key step in assessing the repaired valve durability. Finite element models have been widely used for stress analysis of the mitral valve [1–3]. Most of these models, however, have employed only basic constitutive models and utilized simplified valve geometry. Above all, they have ignored the complex microstructure of the MV, which is the critical physical link between organ level stresses and cellular function. Thus, in this work we developed an initial method to develop an accurate geometrical model of the ovine MV and map the fiber structure for the purposes of developing high fidelity computational meshes of the MV.
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Infarct expansion initiates and sustains adverse left ventricular (LV) remodeling after myocardial infarction (MI) and is influenced by temporal changes in infarct material properties. Data from ex vivo biaxial extension testing support... more
Infarct expansion initiates and sustains adverse left ventricular (LV) remodeling after myocardial infarction (MI) and is influenced by temporal changes in infarct material properties. Data from ex vivo biaxial extension testing support this hypothesis; however, infarct material properties have never been measured in vivo. The goal of the current study was to serially quantify the in vivo material properties and fiber orientation of infarcted myocardium over a 12-week period in a porcine model of MI. A combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numeric optimization was used to analyze posterolateral MI. Specifically, properties were determined by minimizing the difference between in vivo strains and volume calculated from MRI and strains and volume predicted by finite element modeling. In 1 week after MI, the infarct region was found to be approximately 20 times stiffer than normal diastolic myocardium. Over the course of 12 weeks, the infarct region became progressively less stiff as the LV dilated and ejection fraction decreased. The infarct thinned by nearly half during the remodeling period, and infarct fiber angles became more circumferentially oriented. The results reported here are consistent with previously described ex vivo biaxial extension studies of infarct material properties and the circumferential change of collagen orientation in posterolateral infarcts. The current study represents a significant advance in that the method used allows for the serial assessment of an individual infarct in vivo over time and avoids the inherent limitations related to the testing of excised tissues.
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Recent long-term studies showed an unsatisfactory recurrence rate of severe mitral regurgitation 3-5 years after surgical repair, suggesting that excessive tissue stresses and the resulting strain-induced tissue failure are potential... more
Recent long-term studies showed an unsatisfactory recurrence rate of severe mitral regurgitation 3-5 years after surgical repair, suggesting that excessive tissue stresses and the resulting strain-induced tissue failure are potential etiological factors controlling the success of surgical repair for treating mitral valve (MV) diseases. We hypothesized that restoring normal MV tissue stresses in MV repair techniques would ultimately lead to improved repair durability through the restoration of MV normal homeostatic state. Therefore, we developed a micro- and macro- anatomically accurate MV finite element model by incorporating actual fiber microstructural architecture and a realistic structure-based constitutive model. We investigated MV closing behaviors, with extensive in vitro data used for validating the proposed model. Comparative and parametric studies were conducted to identify essential model fidelity and information for achieving desirable accuracy. More importantly, for the...
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ABSTRACT Although mitral valve (MV) repair surgeries are commonly performed, their long-term durability has not been completely satisfying. In most cases, failure was a result of disruption at the leaflet, chordae, or annular suture... more
ABSTRACT Although mitral valve (MV) repair surgeries are commonly performed, their long-term durability has not been completely satisfying. In most cases, failure was a result of disruption at the leaflet, chordae, or annular suture lines. These failure modes suggest excessive stress and the resulting tissue damage as etiologic factors. The purpose of this study was to develop a method to better estimate functional dynamic in-vivo stresses in the MV anterior leaflet (AL) midsection. The stress was computed from the dynamic in-vivo strain measured experimentally. Numerous in-vivo and in-vitro studies (e.g. [3, 4]) have been conducted to quantify MV dynamic strain. We used in-vivo strain data obtained from our well-established ovine model [4]. To calculate the in-vivo strain, we employed the actual unloaded state of the tissue as the reference frame, measured for the first time in this study. The AL stress was then computed using our nonlinear structural constitutive model [5].
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There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global... more
There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Global...
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The purpose of this study was to quantify myocardial three-dimensional (3D) principal strains as the left ventricle (LV) remodels after myocardial infarction (MI). Serial quantification of myocardial strains is important for understanding... more
The purpose of this study was to quantify myocardial three-dimensional (3D) principal strains as the left ventricle (LV) remodels after myocardial infarction (MI). Serial quantification of myocardial strains is important for understanding the mechanical response of the LV to MI. Principal strains convert the 3D LV wall-based strain matrix with three normal and three shear elements, to a matrix with three nonzero normal elements, thereby eliminating the shear elements, which are difficult to physically interpret. The study was designed to measure principal strains of the remote, border zone, and infarct regions in a porcine model of post-MI LV remodeling. Magnetic resonance imaging was used to measure function and strain at baseline, 1 week, and 4 weeks after infarct. Principal strain was measured using 3D acquisition and the optical flow method for displacement tracking. Principal strains were altered as the LV remodeled. Maximum principal strain magnitude decreased in all regions, ...
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ABSTRACT Although mitral valve (MV) repair surgeries are commonly performed, their long-term durability has not been completely satisfying. In most cases, failure was a result of disruption at the leaflet, chordae, or annular suture... more
ABSTRACT Although mitral valve (MV) repair surgeries are commonly performed, their long-term durability has not been completely satisfying. In most cases, failure was a result of disruption at the leaflet, chordae, or annular suture lines. These failure modes suggest excessive stress and the resulting tissue damage as etiologic factors. The purpose of this study was to develop a method to better estimate functional dynamic in-vivo stresses in the MV anterior leaflet (AL) midsection. The stress was computed from the dynamic in-vivo strain measured experimentally. Numerous in-vivo and in-vitro studies (e.g. [3, 4]) have been conducted to quantify MV dynamic strain. We used in-vivo strain data obtained from our well-established ovine model [4]. To calculate the in-vivo strain, we employed the actual unloaded state of the tissue as the reference frame, measured for the first time in this study. The AL stress was then computed using our nonlinear structural constitutive model [5].
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ABSTRACT Many surgeons have come to view mitral valve (MV) repair as the treatment of choice in patients with mitral regurgitation (MR) [1]. According to recent long-term studies, the recurrence of significant MR after repair may be much... more
ABSTRACT Many surgeons have come to view mitral valve (MV) repair as the treatment of choice in patients with mitral regurgitation (MR) [1]. According to recent long-term studies, the recurrence of significant MR after repair may be much higher than previously believed, particularly in patients with (ischemic mitral regurgitation) IMR [2]. We hypothesize that the restoration of homeostatic normal MV leaflet tissue stress in IMR repair techniques ultimately leads to improved repair durability. Therefore, the objective of this study is to develop a novel micro-anatomically accurate 3D finite element (FE) model that incorporates detailed collagen fiber architecture, accurate constitutive models, and micro-anatomically realistic valvular geometry to investigate the functional mitral valve and to aid in the assessment of the mitral valve repairs, especially the linking between the interstitial cellular deformations at the cellular level, the mechanobiological behaviors at the tissue level and the organ level mechanical responses as normal and repaired mitral valves maintaining their homeostatic state.
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Apoptosis induced mitochondrial destruction and dysfunction has been shown to play an important role in the pathogenesis of both acute cardiac ischemia-reperfusion injury and chronic myocardial infarction-induced ventricular remodeling.... more
Apoptosis induced mitochondrial destruction and dysfunction has been shown to play an important role in the pathogenesis of both acute cardiac ischemia-reperfusion injury and chronic myocardial infarction-induced ventricular remodeling. Unfortunately this understanding has not translated into effective therapeutic strategies for either condition-mostly due to an inability to assess mitochondrial dysfunction/apoptosis effectively in humans. All current measures of apoptosis are pseudo-quantitative and require invasive tissue biopsy. Our group has developed an optical, non-tissue destructive catheter based device that allows the quantitative regional assessment of this pathological process in vivo. This instrument has been designed to acquire fluorescence signals of intrinsic mitochondrial fluorophores, Nicotinamide Adenine Dinucleotide (NAD) and Flavoprotein (FP). The normalized ratio of these fluorophores (FP/FP+NADH) called the redox ratio, is an indicator of the in vivo mitochondr...
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To evaluate the accuracy, reproducibility, and contouring time of RV mass in end-systole (ES) and end-diastole (ED). Magnetic resonance imaging (MRI) has been shown to be accurate and reproducible for the evaluation of right ventricular... more
To evaluate the accuracy, reproducibility, and contouring time of RV mass in end-systole (ES) and end-diastole (ED). Magnetic resonance imaging (MRI) has been shown to be accurate and reproducible for the evaluation of right ventricular (RV) volume and function. RV mass, assessed in end-diastolic (ED) phase, is one of the least reproducible variables. The choice of end-systolic (ES) phase could offer an alternative to improve reproducibility, since the selection of the basal slice and the visualization of the usually thin RV wall are easier in this phase. To evaluate accuracy, 11 sheep were imaged in vivo and their RV free walls were weighed after removing epicardial fat. To evaluate reproducibility, 30 normal subjects and 30 subjects with pulmonary arterial hypertension (PAH) were imaged and interobserver and intraobserver variabilities were assessed in the ES and the ED. Segmentation time was recorded after visual selection of ES and ED phases. ES RV mass measurement has less abso...
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Ischemic mitral regurgitation (IMR), the incidence of which is increasing, results from annular and subvalvular remodeling after myocardial infarction (MI). Although a sheep model of IMR has been used extensively over the past two... more
Ischemic mitral regurgitation (IMR), the incidence of which is increasing, results from annular and subvalvular remodeling after myocardial infarction (MI). Although a sheep model of IMR has been used extensively over the past two decades, the ventricular, coronary and leaflet anatomy in sheep is significantly different from that in humans. In contrast, pigs are more similar to humans with regard to these parameters, and therefore may serve as a better animal to test emerging new technologies designed to treat IMR. Twenty-nine pigs (body weight 30-35 kg) underwent left thoracotomy and ligation of the mid main circumflex and distal right posterior descending coronary arteries to create a posterolateral MI. Of these pigs, 18 were used for acute data acquisition, while 11 surviving animals in the chronic group were assessed at eight weeks after MI. Real-time three-dimensional echocardiography was performed at baseline, and at 30 min and eight weeks after MI, to assess geometric changes...
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Mechanisms of bleeding common to virtually all patients after heart surgery are platelet dysfunction, enhanced fibrinolysis, dilution of all components of the coagulation system, and the presence of heparin and protamine. The use of... more
Mechanisms of bleeding common to virtually all patients after heart surgery are platelet dysfunction, enhanced fibrinolysis, dilution of all components of the coagulation system, and the presence of heparin and protamine. The use of warfarin is increasing in patients with heart disease requiring surgery. The replenishment of vitamin K-dependent factors beyond a normal prothrombin time is not assessable, and the dilution associated with cardiopulmonary bypass can reach coagulopathic levels. Optimal preoperative preparation is required and intraoperative therapy initiated when indicated. Individualized heparin and protamine dosing, antifibrinolytic drug administration, minimization of blood loss and dilution, and minimal time on cardiopulmonary bypass are basic adjuncts to meticulous surgical hemostasis. When bleeding is observed in the postoperative period, a sequential assessment of the probable cause leads to initial therapy while laboratory test results are obtained. Ongoing asses...
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ABSTRACT Heart disease causes about 15% of deaths in the United States; about two thirds of these cases are due to coronary artery disease [1]. Post myocardial infarction (MI), left ventricular (LV) remodeling ensues and leads to... more
ABSTRACT Heart disease causes about 15% of deaths in the United States; about two thirds of these cases are due to coronary artery disease [1]. Post myocardial infarction (MI), left ventricular (LV) remodeling ensues and leads to geometric changes that result in dilation and thinning of the myocardial wall. This increases stress in the infarct and healthy tissue and ultimately results in heart failure. Injectable bulking agents have recently emerged as a promising therapy to address these maladaptive changes. As suggested by the Law of Laplace, thickening of the myocardium should decrease stress on the heart and potentially attenuate the negative effects of LV remodeling [2].
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Assessment of left ventricular (LV) function with an emphasis on contractility has been a challenge in cardiac mechanics during the recent decades. The LV function is usually described by the LV pressure-volume (P-V) diagram. The standard... more
Assessment of left ventricular (LV) function with an emphasis on contractility has been a challenge in cardiac mechanics during the recent decades. The LV function is usually described by the LV pressure-volume (P-V) diagram. The standard P-V diagrams are easy to interpret but difficult to obtain and require invasive instrumentation for measuring the corresponding volume and pressure data. In the present study, we introduce a technique that can estimate the viscoelastic properties of the LV based on harmonic behavior of the ventricular chamber and it can be applied non-invasively as well. The estimation technique is based on modeling the actual long axis displacement of the mitral annulus plane toward the cardiac base as a linear damped oscillator with time-varying coefficients. The time-varying parameters of the model were estimated by a standard recursive linear least squares (RLLS) technique. LV stiffness at end-systole and end diastole was in the range of 61.86-136.00 dyne/g.cm ...
Research Interests: Viscoelasticity, Biomechanics, Elasticity, Humans, Computer Simulation, and 15 moreMovement, Left Ventricular Assist Device, Animals, Viscosity, Oscillations, Cardiovascular system, Mechanical Stress, Tissue Doppler Imaging, Reproducibility of Results, Harmonic Oscillators, Biological clocks, Sensitivity and Specificity, Mr Imaging, Left Ventricle, and Viscoelastic Properties
The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry... more
The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry and dimensions published in the literature. We also developed simulated CBAV geometry based on the most common geometry present in patients with CBAV that is published in the literature. We employed a constitutive relationship for the leaflet material from the previously published experimental data of fresh porcine aortic valve leaflet specimens for the analysis. We performed dynamic finite element (FE) structural analysis of the valves in the aortic position in order to compute the strain and stress distribution on the leaflets of the tri-leaflet valve and the CBAV models. Our results showed that large changes in the computed in-plane leaflet strain and stress occurred with variations in the geometry of the simulated CBAV whereas changes due to al...
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Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR). A total of 35 patients... more
Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR). A total of 35 patients undergoing elective surgical AVR under cardiopulmonary bypass was enrolled in the study. Intraoperative RT-3D TEE was used prospectively to acquire volumetric echocardiographic datasets immediately before and after AVR. The 3D echocardiographic data were analyzed offline using TomTec Mitral Valve Assessment software to assess changes in specific mitral annular geometric parameters. Datasets were successfully acquired and analyzed for all patients. A significant reduction was noted in the mitral annular area (-16.3%, p < 0.001), circumference (-8.9%, p < 0.001) and the anteroposterior (-6.3%, p = 0.019) and anterolateral-posteromedial (-10.5%, p < 0.001) diameters. A greater reduction was noted in the anterior annulus length compared to the po...
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ABSTRACT Improvements in mitral valve (MV) treatments are dependent on a complete understanding of the function, mechanical properties, and underlying mechanobiological responses of the MV. While finite element analyses have provided... more
ABSTRACT Improvements in mitral valve (MV) treatments are dependent on a complete understanding of the function, mechanical properties, and underlying mechanobiological responses of the MV. While finite element analyses have provided insight into the cooperative interactions of MV components [1], a lack of quantitative information on the dynamic MV boundary conditions and synchronous leaflet deformation limits present modeling efforts [2]. In this work, we utilized high fidelity transducers implanted in the ovine MV annulus and anterior leaflet to quantify the complete 3D MV kinematics in synchrony. Additionally, effects of systolic blood pressure (SBP) variations on annular and leaflet deformation were investigated.
ABSTRACT Several investigators have been successful in reducing the adverse left ventricular (LV) remodeling and expansion that exists in response to myocardial infarction (MI) via the use of various restraints, such as knitted... more
ABSTRACT Several investigators have been successful in reducing the adverse left ventricular (LV) remodeling and expansion that exists in response to myocardial infarction (MI) via the use of various restraints, such as knitted polypropylene meshes [1] and injectable materials [2]. A recent finite element model simulation of the theoretical impact of injection of a material into the myocardium after MI confirmed the suspected stress reduction potential of intramyocardial infarct stiffening with an acellular, non-contractile material. As peak LV wall stress has been implicated in the pathogenesis of post-infarct LV remodeling, this approach to LV wall stress reduction has significant therapeutic potential [3].
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Research Interests: Cardiovascular, Elasticity, Computer Simulation, Sheep, Left Ventricular Assist Device, and 13 moreBlood Pressure, Animals, Viscosity, Oscillations, Tissue Doppler Imaging, Cardiovascular Engineering, Indexation, Linear Regression, Mr Imaging, Blood Flow Velocity, Time varying, Left Ventricle, and Viscoelastic Properties
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Data obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV)... more
Data obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV) function or during an arrhythmia. Multi-slice, short axis cine and real-time golden-angle radial CMR data was collected in 22 clinical patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized active contour segmentation (ACS) software was validated via comparison to manual segmentation on clinically accepted software. For each image in the 2D acquisitions, slice volume was calculated and global LV volumes were estimated via summation across the LV using multiple slices. Real-time imaging data was reconstructed using different image exposure times and frame rates to evaluate the effect of temporal resolution on measured function in each slice via ACS. Finally, global volumetric function of ectopic and non-ectopic beats was mea...