Biomedical Engineering and Bioengineering Commons^™

Computational Simulations For Aortic Coarctation: Representative Results From A Sampling Of Patients, John F. Ladisa, Alberto Figueroa, Irene E. Vignon-Clementel, Hyun Jin Kim, Nan Xiao, Laura M. Ellwein, Frandics P. Chan, Jeffrey A. Feinstein, Charles A. Taylor

Biomedical Engineering Faculty Research and Publications

Treatments for coarctation of the aorta (CoA) can alleviate blood pressure (BP) gradients(D), but long-term morbidity still exists that can be explained by altered indices of hemodynamics and biomechanics. We introduce a technique to increase our understanding of these indices for CoA under resting and nonresting conditions, quantify their contribution to morbidity, and evaluate treatment options. Patient-specific computational fluid dynamics (CFD) models were created from imaging and BP data for one normal and four CoA patients (moderate native CoA: D12 mmHg, severe native CoA: D25 mmHg and postoperative end-to-end and end-to-side patients: D0 mmHg). Simulations incorporated vessel deformation, downstream vascular …

Computational Simulations Demonstrate Altered Wall Shear Stress In Aortic Coarctation Patients Previously Treated By Resection With End-To-End Anastomosis, John F. Ladisa, Ronak Jashwant Dholakia, Alberto Figueroa, Irene E. Vignon-Clementel, Frandics P. Chan, Margaret M. Samyn, Joseph Richard Cava, Charles A. Taylor, Jeffrey A. Feinstein

Biomedical Engineering Faculty Research and Publications

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity.

Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear …

Spatial And Temporal Variation Of Rod Photoreceptor Reflectance In The Human Retina, Robert F. Cooper, Adam M. Dubis, Ashavini M. Pavaskar, Jungtae Rha, Alfredo Dubra, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

Using adaptive optics imaging tools to image the living retina, numerous investigators have reported temporal fluctuation in the reflectivity of individual cone photoreceptors. In addition, there is cone-to-cone (spatial) variation in reflectivity. As it has only recently become possible to image the complete rod photoreceptor mosaic in the living human retina, we sought to characterize the reflectivity of individual rods and compare their behavior to that of foveal/parafoveal cones. Across two subjects, we were able to successfully track the reflectance behavior of 1,690 rods and 1,980 cones over 12 hours. Rod and cone photoreceptors showed similar regional and temporal variability …

Carotid Plaque Regression Following 6-Month Statin Therapy Assessed By 3t Cardiovascular Magnetic Resonance: Comparison With Ultrasound Intima Media Thickness, Raymond Q. Migrino, Mark Bowers, Leanne Harmann, Robert W. Prost, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Background

Cardiovascular magnetic resonance (CMR) allows volumetric carotid plaque measurement that has advantage over 2-dimensional ultrasound (US) intima-media thickness (IMT) in evaluating treatment response. We tested the hypothesis that 6-month statin treatment in patients with carotid plaque will lead to plaque regression when measured by 3 Tesla CMR but not by IMT.

Methods

Twenty-six subjects (67 ± 2 years, 7 females) with known carotid plaque (> 1.1 mm) and coronary or cerebrovascular atherosclerotic disease underwent 3T CMR (T1, T2, proton density and time of flight sequences) and US at baseline and following 6 months of statin therapy (6 had initiation, …

Global Flow Impacts Time-To-Passage Judgments Based On Local Motion Cues, Scott A. Beardsley, Elif M. Sikoglu, Heiko Hecht, Lucia M. Vaina

Biomedical Engineering Faculty Research and Publications

We assessed the effect of the coherence of optic flow on time-to-passage judgments in order to investigate the strategies that observers use when local expansion information is reduced or lacking. In the standard display, we presented a cloud of dots whose image expanded consistent with constant observer motion. The dots themselves, however, did not expand and were thus devoid of object expansion cues. Only the separations between the dots expanded. Subjects had to judge which of two colored target dots, presented at different simulated depths and lateral displacements would pass them first. Image velocities of the target dots were chosen …

Differential Responses Of Targeted Lung Redox Enzymes To Rat Exposure To 60 Or 85% Oxygen, Zhuohui Gan, David L. Roerig, Anne V. Clough, Said H. Audi

Biomedical Engineering Faculty Research and Publications

Rat exposure to 60% O₂ (hyper-60) or 85% O₂ (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O₂. The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH₂), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH₂ and DQ were measured. …

Noninvasive Imaging Of The Human Rod Photoreceptor Mosaic Using A Confocal Adaptive Optics Scanning Ophthalmoscope, Alfredo Dubra, Yusufu N. Sulai, Jennifer L. Norris, Robert F. Cooper, Adam M. Dubis, David R. Williams, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by …

Effect Of Ankle Orientation On Heel Loading And Knee Stability For Post-Stroke Individuals Wearing Ankle-Foot Orthoses, M. Barbara Silver-Thorn

Biomedical Engineering Faculty Research and Publications

Background: Those who experience lower extremity weakness or paralysis following a stroke often exhibit gait deviations caused by the inability to completely lift their foot during swing. An ankle-foot orthosis (AFO) is commonly prescribed for individuals post stroke with this mobility impairment.

Study design: Randomized controlled trial.

Objectives: To determine whether significant differences could be observed in post-stroke individuals ambulating with an experimental AFO set at three different ankle orientations.

Methods: Gait analysis was conducted for eight post-stroke individuals ambulating with an experimental AFO set in three different randomly selected ankle orientations: 5° dorsiflexion, 5° plantarflexion, and neutral alignment. Temporospatial …

Salen Mn Complexes Mitigate Radiation Injury In Normal Tissues, Rosalind A. Rosenthal, Brian Fish, Richard P. Hill, Karl D. Huffman, Zelmira Lazarova, Javed Mahmood, Meetha Medhora, Robert C. Molthen, John E. Moulder, Stephen T. Sonis, Philip J. Tofilon, Susan R. Doctrow

Biomedical Engineering Faculty Research and Publications

Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it …

A Rapid And Computationally Inexpensive Method To Virtually Implant Current And Next-Generation Stents Into Subject-Specific Computational Fluid Dynamics Models, Timothy J. Gundert, Shawn C. Shadden, Andrew R. Williams, Bon-Kwon Koo, Jeffrey A. Feinstein, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Computational modeling is often used to quantify hemodynamic alterations induced by stenting, but frequently uses simplified device or vascular representations. Based on a series of Boolean operations, we developed an efficient and robust method for assessing the influence of current and next-generation stents on local hemodynamics and vascular biomechanics quantified by computational fluid dynamics. Stent designs were parameterized to allow easy control over design features including the number, width and circumferential or longitudinal spacing of struts, as well as the implantation diameter and overall length. The approach allowed stents to be automatically regenerated for rapid analysis of the contribution of …

What Is Inverse-Geometry Ct?, Taly Gilat Schmidt

Biomedical Engineering Faculty Research and Publications

Inverse-geometry computed tomography (IGCT) systems are being developed to provide improved volumetric imaging. In conventional multislice CT systems, x-rays are emitted from a small area and irradiate a large-area detector. In an IGCT system, x-ray sources are distributed over a large area, with each beam irradiating a small-area detector. Therefore, in the inverse geometry, a series of narrow x-ray beams are switched on and off while the gantry rotates. In conventional CT geometry, cone-beam and scatter artifacts increase with the imaged volume thickness. An inverse geometry may be less susceptible to scatter effects, because only a fraction of the field …

Mitochondrial Approaches To Protect Against Cardiac Ischemia And Reperfusion Injury, Amadou K.S. Camara, Martin Bienengraeber, David F. Stowe

Biomedical Engineering Faculty Research and Publications

The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances …

Micro-Ct Characterization Of Human Trabecular Bone In Osteogenesis Imperfecta, John Jameson, Carolyne Albert, Peter Smith, Robert C. Molthen, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of …

Race- And Sex-Related Differences In Retinal Thickness And Foveal Pit Morphology, Melissa Wagner-Schuman, Adam M. Dubis, Rick Nordgren, Yuming Lei, Daniel Odell, Hellen Chiao, Eric Weh, William Fischer, Yusufu N. Sulai, Alfredo Dubra, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

Purpose.

To examine sex- and race-associated differences in macular thickness and foveal pit morphology by using spectral-domain optical coherence tomography (SD-OCT).

Methods.

One hundred eighty eyes of 90 healthy patients (43 women, 47 men) underwent retinal imaging with spectral-domain OCT. The lateral scale of each macular volume scan was corrected for individual differences in axial length by ocular biometry. From these corrected volumes, Early Treatment Diabetic Retinopathy Study (ETDRS) grids of retinal thickness were generated and compared between the groups. Foveal morphology was measured with previously described algorithms.

Results.

Compared with the Caucasians, the Africans and African Americans had reduced …

Energy Deposition In The Breast During Ct Scanning: Quantification And Implications For Dose Reduction, Franco Rupcich, Iacovos Kyprianou, Andreu Badal, Taly Gilat Schmidt

Biomedical Engineering Faculty Research and Publications

Studies suggest that dose to the breast leads to a higher lifetime attributable cancer incidence risk from a chest CT scan for women compared to men. Numerous methods have been proposed for reducing dose to the breast during CT scanning, including bismuth shielding, tube current modulation, partial-angular scanning, and reduced kVp. These methods differ in how they alter the spectrum and fluence across projection angle. This study used Monte Carlo CT simulations of a voxelized female phantom to investigate the energy (dose) deposition in the breast as a function of both photon energy and projection angle. The resulting dose deposition …

Effects Of Acute Rho Kinase Inhibition On Chronic Hypoxia-Induced Changes In Proximal And Distal Pulmonary Arterial Structure And Function, Rebecca R. Vanderpool, Ah Ram Kim, Robert C. Molthen, Naomi Chesler

Biomedical Engineering Faculty Research and Publications

Hypoxic pulmonary hypertension (HPH) is initially a disease of the small pulmonary arteries. Its severity is usually quantified by pulmonary vascular resistance (PVR). Acute Rho kinase inhibition has been found to reduce PVR toward control values in animal models, suggesting that persistent pulmonary vasoconstriction is the dominant mechanism for increased PVR. However, HPH may also cause proximal arterial changes, which are relevant to right ventricular (RV) afterload. RV afterload can be quantified by pulmonary vascular impedance, which is obtained via spectral analysis of pulsatile pressure-flow relationships. To determine the effects of HPH independent of persistent pulmonary vasoconstriction in proximal and …

Multimodality Imaging Of Abnormal Vascular Perfusion And Morphology In Preclinical 9l Gliosarcoma Model, Moses M. Darpolor, Robert C. Molthen, Kathleen M. Schmainda

Biomedical Engineering Faculty Research and Publications

This study demonstrates that a dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) perfusion parameter may indicate vascular abnormality in a brain tumor model and reflects an effect of dexamethasone treatment. In addition, X-ray computed tomography (CT) measurements of vascular tortuosity and tissue markers of vascular morphology were performed to investigate the underpinnings of tumor response to dexamethasone.

Reorganization Of Finger Coordination Patterns During Adaptation To Rotation And Scaling Of A Newly Learned Sensorimotor Transformation, Xiaolin Liu, Kristine M. Mosier, Ferdinando A. Mussa-Ivaldi, Maura Casadio, Robert A. Scheidt

Biomedical Engineering Faculty Research and Publications

We examined how people organize redundant kinematic control variables (finger joint configurations) while learning to make goal-directed movements of a virtual object (a cursor) within a low-dimensional task space (a computer screen). Subjects participated in three experiments performed on separate days. Learning progressed rapidly on day 1, resulting in reduced target capture error and increased cursor trajectory linearity. On days 2 and 3, one group of subjects adapted to a rotation of the nominal map, imposed either stepwise or randomly over trials. Another group experienced a scaling distortion. We report two findings. First, adaptation rates and memory-dependent motor command updating …

Visual And Proprioceptive Contributions To Compensatory And Pursuit Tracking Movements In Humans, Megan L. Heenan, Robert A. Scheidt, Scott A. Beardsley

Biomedical Engineering Faculty Research and Publications

An ongoing debate in the field of motor control considers how the brain uses sensory information to guide the formation of motor commands to regulate movement accuracy. Recent research has shown that the brain may use visual and proprioceptive information differently for stabilization of limb posture (compensatory movements) and for controlling goal-directed limb trajectory (pursuit movements). Using a series of five experiments and linear systems identification techniques, we modeled and estimated the sensorimotor control parameters that characterize the human motor response to kinematic performance errors during continuous compensatory and pursuit tracking tasks. Our findings further support the idea that pursuit …

Quantifying Mitochondrial And Plasma Membrane Potentials In Intact Pulmonary Arterial Endothelial Cells Based On Extracellular Disposition Of Rhodamine Dyes, Zhuohui Gan, Said H. Audi, Robert D. Bongard, Kathryn M. Gauthier, Marilyn P. Merker

Biomedical Engineering Faculty Research and Publications

Our goal was to quantify mitochondrial and plasma potential (Δψ_m and Δψ_p) based on the disposition of rhodamine 123 (R123) or tetramethylrhodamine ethyl ester (TMRE) in the medium surrounding pulmonary endothelial cells. Dyes were added to the medium, and their concentrations in extracellular medium ([R_e]) were measured over time. R123 [R_e] fell from 10 nM to 6.6 ± 0.1 (SE) nM over 120 min. TMRE [R_e] fell from 20 nM to a steady state of 4.9 ± 0.4 nM after ∼30 min. Protonophore or high K⁺ concentration ([K⁺]), …

Instrument Independent Diffuse Reflectance Spectroscopy, Bing Yu, Henry L. Fu, Nirmala Ramanujam

Biomedical Engineering Faculty Research and Publications

Diffuse reflectance spectroscopy with a fiber optic probe is a powerful tool for quantitative tissue characterization and disease diagnosis. Significant systematic errors can arise in the measured reflectance spectra and thus in the derived tissue physiological and morphological parameters due to real-time instrument fluctuations. We demonstrate a novel fiber optic probe with real-time, self-calibration capability that can be used for UV-visible diffuse reflectance spectroscopy in biological tissue in clinical settings. The probe is tested in a number of synthetic liquid phantoms over a wide range of tissue optical properties for significant variations in source intensity fluctuations caused by instrument warm …

Cardiac Magnetic Resonance Imaging Can Detect Early Vascular Changes In Children With Type 1 Diabetes (T1dm), Margaret M. Samyn, Pippa Simpson, Michael E. Widlansky, Mary M. Krolikowski, Jennifer Co-Vu, Ronak Jashwant Dholakia, John F. Ladisa, Ramin Alemzadeh

Biomedical Engineering Faculty Research and Publications

No abstract provided.

A Quantitative And Standardized Robotic Method For The Evaluation Of Arm Proprioception After Stroke, Lucia Simo, Claude Ghez, Lior Botzer, Robert A. Scheidt

Biomedical Engineering Faculty Research and Publications

Stroke often results in both motor and sensory deficits, which may interact in the manifested functional impairment. Proprioception is known to play important roles in the planning and control of limb posture and movement; however, the impact of proprioceptive deficits on motor function has been difficult to elucidate due in part to the qualitative nature of available clinical tests. We present a quantitative and standardized method for evaluating proprioception in tasks directly relevant to those used to assess motor function. Using a robotic manipulandum that exerted controlled displacements of the hand, stroke participants were evaluated, and compared with a control …

A Novel Cable-Driven Robotic Training Improves Locomotor Function In Individuals Post-Stroke, Ming Wu, Jill M. Landry, Sheng-Che Yen, Brian D. Schmit, T. George Hornby, Miriam Rafferty

Biomedical Engineering Faculty Research and Publications

A novel cable-driven robotic gait training system has been tested to improve the locomotor function in individuals post stroke. Seven subjects with chronic stroke were recruited to participate in this 6 weeks robot-assisted treadmill training paradigm. A controlled assistance force was applied to the paretic leg at the ankle through a cable-driven robotic system. The force was applied from late stance to mid-swing during treadmill training. Body weight support was provided as necessary to prevent knee buckling or toe drag. Subjects were trained 3 times a week for 6 weeks. Overground gait speed, 6 minute walking distance, and balance were …

Effects Of Wrist Tendon Vibration On Targeted Upper-Arm Movements In Poststroke Hemiparesis, Megan O. Conrad, Robert A. Scheidt, Brian D. Schmit

Biomedical Engineering Faculty Research and Publications

Background. Impaired motor control of the upper extremity after stroke may be related to lost sensory, motor, and integrative functions of the brain. Artificial activation of sensory afferents might improve control of movement by adding excitatory drive to sensorimotor control structures. The authors evaluated the effect of wrist tendon vibration (TV) on paretic upper-arm stability during point-to-point planar movements. Methods. TV (70 Hz) was applied to the forearm wrist musculature of 10 hemiparetic stroke patients as they made center-out planar arm movements. End-point stability, muscle activity, and grip pressure were compared as patients stabilized at the target position …

A Database For Estimating Scanner-Specific Ct Dose, Taly Gilat-Schmidt

Biomedical Engineering Faculty Research and Publications

Purpose: To develop a database for estimating scanner-specific organ dose in a voxelized patient model for any spectral shape and angular tube current modulation setting. The database enables the estimation of organ dose for both existing and novel acquisition techniques without requiring Monte Carlo simulations.

Methods: The transport of monoenergetic photons through three phantoms was simulated with the PENELOPE Monte Carlo radiation transport routines at 5 – 150 keV in 1 keV increments at 1000 projections in 0.36 degree increments. The source-to-detector distance for each simulation was 100 cm, with a source-to-isocenter distance of 50 cm. The lateral and axial …

Biophysical Properties Of The Aorta In Patients With Marfan Syndrome And Related Connective Tissue Disorders: Evaluation With Mri And Computational Fluid Dynamics Modeling, Joseph A. Camarda, Michael G. Earing, Ronak Jashwant Dholakia, Hongfeng Wang, Sung Kwon, John F. Ladisa Jr., Margaret M. Samyn

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Sensory Motor Remapping Of Space In Human-Machine Interfaces, Ferdinando A. Mussa-Ivaldi, Maura Casadio, Zachary C. Danziger, Kristine M. Mosier, Robert A. Scheidt

Biomedical Engineering Faculty Research and Publications

Studies of adaptation to patterns of deterministic forces have revealed the ability of the motor control system to form and use predictive representations of the environment. These studies have also pointed out that adaptation to novel dynamics is aimed at preserving the trajectories of a controlled endpoint, either the hand of a subject or a transported object. We review some of these experiments and present more recent studies aimed at understanding how the motor system forms representations of the physical space in which actions take place. An extensive line of investigations in visual information processing has dealt with the issue …

Incorporating Feedback From Multiple Sensory Modalities Enhances Brain–Machine Interface Control, Aaron J. Suminski, Dennis C. Tkach, Andrew H. Fagg, Nicholas G. Hatsopoulos

Biomedical Engineering Faculty Research and Publications

The brain typically uses a rich supply of feedback from multiple sensory modalities to control movement in healthy individuals. In many individuals, these afferent pathways, as well as their efferent counterparts, are compromised by disease or injury resulting in significant impairments and reduced quality of life. Brain–machine interfaces (BMIs) offer the promise of recovered functionality to these individuals by allowing them to control a device using their thoughts. Most current BMI implementations use visual feedback for closed-loop control; however, it has been suggested that the inclusion of additional feedback modalities may lead to improvements in control. We demonstrate for the …

Aortic Coarctation: Recent Developments In Experimental And Computational Methods To Assess Treatments For This Simple Condition, John F. Ladisa, Charles A. Taylor, Jeffrey A. Feinstein

Biomedical Engineering Faculty Research and Publications

Coarctation of the aorta (CoA) is often considered a relatively simple disease, but long-term outcomes suggest otherwise as life expectancies are decades less than in the average population and substantial morbidity often exists. What follows is an expanded version of collective work conducted by the authors' and numerous collaborators that was presented at the 1st International Conference on Computational Simulation in Congenital Heart Disease pertaining to recent advances for CoA. The work begins by focusing on what is known about blood flow, pressure and indices of wall shear stress (WSS) in patients with normal vascular anatomy from both clinical imaging …