The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood Δ ρ, the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both Δ ρ and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society.

PAC2002: 8719Rr, 8719Hh

A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to 1 G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank–Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations. © 2002 Biomedical Engineering Society.

PAC2002: 8765+y, 8719Bb, 8719Uv, 8719Hh

Left ventricular remodeling during the development of heart failure is a strong predictor of cardiovascular mortality. However, methods to objectively quantify remodeling-associated shape changes are not routinely available but may be possible with new computational anatomy tools. In this study, we analyzed and compared multi-detector computed tomographic (MDCT) images of ventricular shape at end-systole (ES) and end-diastole (ED) to determine whether regional structural characteristics could be identified and, as a proof of principle, whether differences in hearts of patients with anterior myocardial infarction (MI) and ischemic cardiomyopathy (ICM) could be distinguished from those with global nonischemic cardiomyopathy (NICM). MDCT images of hearts from 11 patients (5 with ICM) with ejection fractions (EF) < 35% were analyzed. An average ventricular shape model (template) was constructed for each cardiac phase by bringing heart shapes into correspondence using linear and nonlinear image matching algorithms. Next, transformation fields were computed between the template image and individual heart images in the population. Principal component analysis (PCA) method was used to quantify ventricular shape differences described by the transformation vector fields. Statistical analysis of PCA coefficients revealed significant ventricular shape differences at ED (p = 0.03) and ES (p = 0.03). For validation, a second set of 14 EF-matched patients (8 with ICM) were evaluated. The discrimination rule learned from the training data set was able to differentiate ICM from NICM patients (p = 0.008). Application of a novel shape analysis method to in vivo human cardiac images acquired on a clinical scanner is feasible and can quantify regional shape differences at end-systole in remodeled myopathic human myocardium. This approach may be useful in identifying differences in the remodeling process between ICM and NICM populations and possibly in differentiating the populations.

Potential-based inverse electrocardiography is a method for the noninvasive computation of epicardial potentials from measured body surface electrocardiographic data. From the computed epicardial potentials, epicardial electrograms and isochrones (activation sequences), as well as repolarization patterns can be constructed. We term this noninvasive procedure Electrocardiographic Imaging (ECGI). The method of choice for computing epicardial potentials has been the Boundary Element Method (BEM) which requires meshing the heart and torso surfaces and optimizing the mesh, a very time-consuming operation that requires manual editing. Moreover, it can introduce mesh-related artifacts in the reconstructed epicardial images. Here we introduce the application of a meshless method, the Method of Fundamental Solutions (MFS) to ECGI. This new approach that does not require meshing is evaluated on data from animal experiments and human studies, and compared to BEM. Results demonstrate similar accuracy, with the following advantages: 1. Elimination of meshing and manual mesh optimization processes, thereby enhancing automation and speeding the ECGI procedure. 2. Elimination of mesh-induced artifacts. 3. Elimination of complex singular integrals that must be carefully computed in BEM. 4. Simpler implementation. These properties of MFS enhance the practical application of ECGI as a clinical diagnostic tool.

In this study, the relationships between the early and late afterpotentials and velocity and amplitude recovery functions (VRF and ARF) in skeletal muscle were examined using model simulation. A mathematical model of the muscle fiber action potential, that incorporated a tubular slow potassium conductance, was developed and used to simulate muscle fiber action potentials at a range of interpulse intervals. The slow potassium conductance produced an afterhyperpolarization which resulted in supernormal action potential conduction velocity and amplitude for interpulse intervals >7 ms. Increasing the number of conditioning stimuli caused a further increase in conduction velocity and amplitude, and an additional phase of supernormality, with a peak at approximately 100 ms. Positive correlations between instantaneous firing rate and both conduction velocity and amplitude were also observed during simulation of repetitive stimulation of the muscle fiber. The relationships were eliminated when the slow potassium conductance channel was removed from the model. The results suggest that an afterhyperpolarization, possibly due to a slow tubular potassium conductance, could cause the VRF and ARF observed in muscle. They additionally suggest that the positive correlations between instantaneous firing rate, conduction velocity, and amplitude are directly related to the VRF and ARF.

Health disparities are preventable differences in the incidence, prevalence and burden of disease among communities targeted by gender, geographic location, ethnicity and/or socio-economic status. While biomedical research has identified partial origin(s) of divergent burden and impact of disease, the innovation needed to eradicate health disparities in the United States requires unique engagement from biomedical engineers. Increasing awareness of the prevalence and consequences of health disparities is particularly attractive to today’s undergraduates, who have undauntedly challenged paradigms believed to foster inequality. Here, the Department of Biomedical Engineering at The City College of New York (CCNY) has leveraged its historical mission of access-and-excellence to integrate the study of health disparities into undergraduate BME curricula. This article describes our novel approach in a multiyear study that: (i) Integrated health disparities modules at all levels of the required undergraduate BME curriculum; (ii) Developed opportunities to include impacts of health disparities into undergraduate BME research projects and mentored High School summer STEM training; and (iii) Established health disparities-based challenges as BME capstone design and/or independent entrepreneurship projects. Results illustrate the rising awareness of health disparities among the youngest BMEs-to-be, as well as abundant undergraduate desire to integrate health disparities within BME education and training.

In this study the electrical and dielectric properties of wet human cancellous bone from distal tibiae were examined as a function of frequency and direction. The resistance and capacitance of the cancellous bone specimens were measured at near 100% relative humidity. The measurements were made in all three orthogonal directions at discrete frequencies ranging from 120 Hz to 10 MHz using an LCR meter. At a frequency of 100 kHz, the mean resistivity and specific capacitance for the thirty cancellous bone specimens were 500 ohm-cm and 8.64 pF/cm in the longitudinal direction, 613 ohm-cm and 15.25 pF/cm in the anterior-posterior direction, and 609 ohm-cm and 14.64 pF/cm in the lateral-medial direction. All electrical and dielectric properties except the resistivity and the impedance were highly frequency dependent for the frequency range tested. All electrical and dielectric properties were transversely isotropic as the values for the longitudinal direction were different from values obtained for the two transverse directions and properties in the two transverse directions were approximately similar.

The discrimination of ventricular tachycardias with 1:1 retrograde conduction from sinus tachycardia still remains a challenge for rate based algorithms commonly used in dual-chamber implantable cardioverter defibrillators. Morphology based analysis techniques for a classification of antegrade and retrograde atrial activation patterns can be used to cope with this problem. Here time-domain template matching techniques are known approaches. However, a time-domain representation of endocardial electrograms is not optimal for classification tasks as the dimensionality of the underlying signal space is high and features being irrelevant for a signal characterization are involved in the analysis. Therefore, the aim of this study is to develop an enhanced morphological analysis tool for a classification of antegrade and retrograde atrial activation by using a transform domain representation of endocardial electrograms. For this, we applied an adapted wavelet-packet decomposition to extract discriminating features in endocardial electrograms representing antegrade and retrograde activation patterns. Further, a feed-forward neural network was utilized to produce a classification based on the extracted information. In using our hybrid method, no false classification of the physiological and pathological cardiac state was made. It is concluded that the proposed classification scheme represents a highly efficient approach for a classification of antegrade and retrograde atrial activation. © 2001 Biomedical Engineering Society.

PAC01: 8719Nn, 8719Hh, 8780Tq, 0705Mh

Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano- and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.