Biomedical Engineering and Bioengineering Commons^™

Quantification Of Thoracic Aorta Blood Flow By Magnetic Resonance Imaging During Supine Cycling Exercise Of Increasing Intensity, Laura M. Ellwein, John F. Ladisa, Stacy Leibham, Sheila M. Schindler-Ivens, Margaret M. Samyn

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Theranostic Oxygen Delivery Using Ultrasound And Microbubbles, James J. Kwan, Mehmet Kaya, Mark A. Borden, Paul A. Dayton

Biomedical Engineering and Sciences Faculty Publications

Means to overcome tumor hypoxia have been the subject of clinical investigations since the 1960’s; however these studies have yet to find a treatment which is widely accepted. It has been known for nearly a century that hypoxic cells are more resistant to radiotherapy than aerobic cells, and tumor hypoxia is a major factor leading to the resistance of tumors to radiation treatment as well as several cytotoxic agents. In this manuscript, the application of ultrasound combined with oxygen-carrier microbubbles is demonstrated as a method to locally increase dissolved oxygen. Microbubbles can also be imaged by ultrasound, thus providing the …

Mechanical Properties And Tensile Failure Analysis Of Novel Bio-Absorbable Mg-Zn-Cu And Mg-Zn-Se Alloys For Endovascular Applications, Dharam Persaud, Noah Budiansky, Anthony J. Mcgoron

Department of Biomedical Engineering Faculty Publications

In this paper, the mechanical properties and tensile failure mechanism of two novel bio-absorbable as-cast Mg-Zn-Se and Mg-Zn-Cu alloys for endovascular medical applications are characterized. Alloys were manufactured using an ARC melting process and tested as-cast with compositions of Mg-Zn-Se and Mg-Zn-Cu, being 98/1/1 wt.% respectively. Nanoindentation testing conducted at room temperature was used to characterize the elastic modulus (E) and surface hardness (H) for both the bare alloys and the air formed oxide layer. As compared to currently available shape memory alloys and degradable as-cast alloys, these experimental alloys possess superior as-cast mechanical properties that can increase their biocompatibility, …

Comparison Of 4d Phase-Contrast Mri Flow Measurements To Computational Fluid Dynamics Simulations Of Cerebrospinal Fluid Motion In The Cervical Spine, Theresia Yiallourou, Jan Robert Kroger, Nikolaos Stergiopulos, David Maintz, Bryn A. Martin, Alexander C. Bunck

Mechanical Engineering Faculty Research

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes …

Role Of Epidermal Growth Factor-Triggered Pi3k/Akt Signaling In The Migration Of Medulloblastoma-Derived Cells, Veronica Dudu, Richard A. Able, Jr., Veronica Rotari, Qingjun Kong, Maribel Vazquez

Publications and Research

Medulloblastoma (MB) is the most common brain cancer diagnosed among children. The cellular pathways that regulate MB invasion in response to environmental cues remain incompletely understood. Herein, we examine the migratory response of human MB-derived Daoy cells to different concentration profiles of Epidermal Growth Factor (EGF) using a microfluidic system. Our findings provide the first quantitative evidence that EGF concentration gradients modulate the chemotaxis of MB-derived cells in a dose-dependent manner via the EGF receptor (EGF-R). Data illustrates that higher concentration gradients caused increased number of cells to migrate. In addition, our results show that EGF-induced receptor phosphorylation triggered the …

On The Importance Of Modeling Stent Procedure For Predicting Arterial Mechanics, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

The stent-artery interactions have been increasingly studied using the finite element method for better understanding of the biomechanical environment changes on the artery and its implications. However, the deployment of balloon-expandable stents was generally simplified without considering the balloon-stent interactions, the initial crimping process of the stent, its overexpansion routinely used in the clinical practice, or its recoil process. In this work, the stenting procedure was mimicked by incorporating all the above-mentioned simplifications. The impact of various simplifications on the stent-induced arterial stresses was systematically investigated. The plastic strain history of stent and its resulted geometrical variations, as well as …

Altered Hemodynamics, Endothelial Function, And Protein Expression Occur With Aortic Coarctation And Persist After Repair, Arjun Menon, Thomas J. Eddinger, Hongfeng Wang, David C. Wendell, Jeffrey M. Toth, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both …

Functional Classification Of Skeletal Muscle Networks. I. Normal Physiology, Yu Wang, John Winters, Shankar Subramaniam

Biomedical Engineering Faculty Research and Publications

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca …

The Effect Of Cone Opsin Mutations On Retinal Structure And The Integrity Of The Photoreceptor Mosaic, Joseph Carroll, Alfredo Dubra, Jessica C. Gardner, Liliana Mizrahi-Meissonnier, Robert F. Cooper, Adam M. Dubis, Rick Nordgren, Mohamed Genead, Thomas B. Connor Jr., Kimberly E. Stepien, Dror Sharon, David M. Hunt, Eyal Banin, Alison J. Hardcastle, Anthony T. Moore, David R. Williams, Gerald Fishman, Jay Neitz, Maureen Neitz, Michel Michaelides

Biomedical Engineering Faculty Research and Publications

Purpose.

To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations.

Methods.

Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array.

Results.

While disruptions in retinal lamination and cone mosaic structure were observed …

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness And Oguchi Disease, Pooja Godara, Robert F. Cooper, Panagiotis I. Sergouniotis, Melissa A. Diederichs, Megan R. Streb, Mohamed Genead, J. Jason Mcanany, Andrew R. Webster, Anthony T. Moore, Adam M. Dubis, Maureen Neitz, Alfredo Dubra, Edwin M. Stone, Gerald A. Fishman, Dennis P. Han, Michel Michaelides, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

Purpose

To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease.

Design

Prospective, observational case series.

Methods

We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer …

Preliminary Investigation Of Residual Limb Plantarflexion And Dorsiflexion Muscle Activity During Treadmill Walking For Trans-Tibial Amputees, M. Barbara Silver-Thorn, Thomas Current, Benjamin Kuhse

Biomedical Engineering Faculty Research and Publications

Background: Novel powered prosthetic ankles currently incorporate finite state control, using kinematic and kinetic sensors to differentiate stance and swing phases/sub-phases and control joint impedance and position or torque. For more intuitive control, myoelectric control of the ankle using the remnant residual limb dorsiflexors and plantarflexors, perhaps in concert with kinetic and kinematic sensors, may be possible.

Objective: The specific research objective was to assess the feasibility of using myoelectric control of future active or powered prosthetic ankle joints for trans-tibial amputees.

Study Design: The project involved human subject trials to determine whether current techniques of myoelectric control of upper …

Diffusion Tensor Imaging And Tractography In Brown-Sequard Syndrome, A. Vendatam, Michael B. Jirjis, Brian D. Schmit, M. D. Budde, J. L. Ulmer, Mei Wang, S. N. Kurpad

Biomedical Engineering Faculty Research and Publications

This report illustrates the utility of DTI and DTT in delineating regions of cord injury in two patients with traumatic Brown-Sequard syndrome. Our results indicate that DTI provides clinically relevant information that supplements conventional MR imaging for patients with acute SCI.

Differential Lung Uptake Of 99mtc-Hexamethylpropyleneamine Oxime And 99mtc-Duramycin In The Chronic Hyperoxia Rat Model, Anne V. Clough, Said H. Audi, Steven Thomas Haworth, David L. Roerig

Biomedical Engineering Faculty Research and Publications

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of ^99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas ^99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods: Male Sprague–Dawley rats were preexposed to either normoxia (21% O …

Implementation Of Magnetic Resonance Elastography For The Investigation Of Traumatic Brain Injuries, Thomas Boulet

Department of Engineering Mechanics: Dissertations, Theses, and Student Research

Magnetic resonance elastography (MRE) is a potentially transformative imaging modality allowing local and non-invasive measurement of biological tissue mechanical properties. It uses a specific phase contrast MR pulse sequence to measure induced vibratory motion in soft material, from which material properties can be estimated. Compared to other imaging techniques, MRE is able to detect tissue pathology at early stages by quantifying the changes in tissue stiffness associated with diseases. In an effort to develop the technique and improve its capabilities, two inversion algorithms were written to evaluate viscoelastic properties from the measured displacements fields. The first one was based on …

Reducing In-Stent Restenosis Through Novel Stent Flow Field Augmentation, Eoin Murphy, Fergal Boyle

Articles

In-stent restenosis (ISR), manifested as a re-narrowing of the arterial lumen post-implantation of a stent, is a detrimental limitation of stent technology. Understanding and consequently devising ways of reducing the frequency of ISR has been a continuing goal of research into improved stent designs. The biological processes that can lead to ISR have been found to be partially flow dependent with the local hemodynamics at the arterial wall of crucial importance. This paper investigates these biological processes and their instigating factors. Furthermore, the history and theory behind three stent technologies which endeavour to reduce ISR rates through stent flow field …

Fabrication Of Cao-Nao-Sio2/Tio2 Scaffolds For Surgical Applications, A. W. Wren, A. Coughlan, K. E. Smale, S. T. Misture, B. P. Mahon, O. M. Clarkin, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

A series of titanium (Ti) based glasses were formulated (0.62 SiO₂-0.14 Na₂O-0.24 CaO, with 0.05 mol% TiO₂ substitutions for SiO₂) to develop glass/ceramic scaffolds for bone augmentation. Glasses were initially characterised using X-ray diffraction (XRD) and particle size analysis, where the starting materials were amorphous with 4.5 μm particles. Hot stage microscopy and high temperature XRD were used to determine the sintering temperature (̃700 °C) and any crystalline phases present in this region (Na₂Ca₃Si₆O₁₆, combeite and quartz). Hardness testing revealed that the Ti-free control (ScC- …

Morphometric, Biochemical, And Raman Spectral Analyses Of Muscle Damage In Patients With Peripheral Arterial Disease: Providing Objective Criteria For Diagnosis And Treatment Monitoring, Kim Cluff

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Peripheral arterial disease (PAD), which affects approximately 10 million Americans, is characterized by atherosclerosis of the non-coronary arteries. PAD produces a progressive accumulation of ischemic injury to the limbs that is reflected in a gradual worsening in the myofiber morphology and oxidative damage in the gastrocnemius muscle. In this study, we evaluated the hypothesis that quantitative morphological and biochemical parameters of gastrocnemius myofibers change in a consistent manner during the progression of PAD, provide an objective grading of muscle degeneration in the ischemic limb, and correlate to clinical stage of PAD. Myofiber morphometrics were determined precisely with mathematical equations that …

Application Of Response Surface Methodology And Central Composite Design For 5p12-Rantes Expression In The Pichia Pastoris System, Frank M. Fabian

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Pichia pastoris has demonstrated the ability to express high levels of recombinant heterologous proteins. Protein expression is enhanced during fermentation at high cell density. However, the level of expression is mainly regulated by fermentation operation factors. This research is directed to investigate the effect of methanol growth rate, temperature and pH in the expression of the total 5P12-Rantes concentration, expression of active 5P12-Rantes and Specific yield using the response surface methodology and central composite design.

The response surface methodology, RSM, has been used successfully used by Zhang, W. and Ian, M. to optimize the cell density and fermentation process. The …

Compression Transmission Collar For Fastening, Patrick Atkinson

Mechanical Engineering Patents

A compression transmission collar apparatus (20) for implantation into a bone (22) with a hole (28) having a hole wall (32) comprising an intramedullary nail (34) defining a bore (40) and a threaded fastener (42) and a compression transmission collar (58) including an exterior face (64) and a top edge (60) and a bottom edge (62) and a first end (70) intersecting the top edge (60) at an acute angle (α₁) and …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …

Reviewing The American University Law Review On Extraterritoriality: A Critical Response To Viki Economides, Note, Tianrui Group Co. V. Itc: The Dubious Status Of Extraterritoriality And The Domestic Industry Requirement Requirement Of Section 337(Link), Jonathan Stroud

Articles in Law Reviews & Other Academic Journals

Recently, the Federal Circuit upheld the Commission’s decision to exclude goods based on a trade secret violation that largely happened abroad. The American University Law Review critiqued that decision on two grounds: First, that a presumption against extraterritorial application of U.S. law applied; and second, that licensing alone could not establish a domestic industry. The American University Law Review's critique remains incomplete, however, as the Federal Circuit correctly decided the case for at least two reasons. first, the Federal Circuit correctly applied the “extraterritorial presumption” canon of construction; and second, the recent Federal Circuit decision in InterDigital Communications LLC v. …

Load-Relaxation Properties Of The Human Trunk In Response To Prolonged Flexion: Measuring And Modeling The Effect Of Flexion Angle, Nima Toosizadeh, Maury A. Nussbaum, Babak Bazrgari, Michael L. Madigan

Biomedical Engineering Faculty Publications

Experimental studies suggest that prolonged trunk flexion reduces passive support of the spine. To understand alterations of the synergy between active and passive tissues following such loadings, several studies have assessed the time-dependent behavior of passive tissues including those within spinal motion segments and muscles. Yet, there remain limitations regarding load-relaxation of the lumbar spine in response to flexion exposures and the influence of different flexion angles. Ten healthy participants were exposed for 16 min to each of five magnitudes of lumbar flexion specified relative to individual flexion-relaxation angles (i.e., 30, 40, 60, 80, and 100%), during which lumbar flexion …

Noninvasive Optical Characterization Of Muscle Blood Flow, Oxygenation, And Metabolism In Women With Fibromyalgia, Yu Shang, Katelyn Gurley, Brock Symons, Douglas Long, Ratchakrit Srikuea, Leslie J. Crofford, Charlotte A. Peterson, Guoqiang Yu

Biomedical Engineering Faculty Publications

INTRODUCTION: Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.

METHODS: Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily …

First-Order Design Of A Reflective Viewfinder For Adaptive Optics Ophthalmoscopy, Alfredo Dubra, Yusufu N. Sulai

Biomedical Engineering Faculty Research and Publications

Adaptive optics (AO) ophthalmoscopes with small fields of view have limited clinical utility. We propose to address this problem in reflective instruments by incorporating a viewfinder pupil relay designed by considering pupil and image centering and conjugation. Diverting light from an existing pupil optical relay to the viewfinder relay allows switching field of view size. Design methods that meet all four centering and conjugation conditions using either a single concave mirror or with two concave mirrors forming an off-axis afocal telescope are presented. Two different methods for calculating the focal length and orientation of the concave mirrors in the afocal …

Tyrosine Nitration Of Voltage-Dependent Anion Channels In Cardiac Ischemia-Reperfusion: Reduction By Peroxynitrite Scavenging, Meiying Yang, Amadou K.S. Camara, Bassam T. Wakim, Yifan Zhou, Ashish K. Gadicherla, Wai-Meng Kwok, David F. Stowe

Biomedical Engineering Faculty Research and Publications

Excess superoxide (O₂⁻) and nitric oxide (NO) forms peroxynitrite (ONOO⁻) during cardiac ischemia reperfusion (IR) injury, which in turn induces protein tyrosine nitration (tyr-N). Mitochondria are both a source of and target for ONOO⁻. Our aim was to identify specific mitochondrial proteins that display enhanced tyr-N after cardiac IR injury, and to explore whether inhibiting O₂⁻/ONOO⁻ during IR decreases mitochondrial protein tyr-N and consequently improves cardiac function. We show here that IR increased tyr-N of 35 and 15 kDa mitochondrial proteins using Western blot analysis with 3-nitrotyrosine antibody. Immunoprecipitation …

Mitigation Of Radiation Induced Pulmonary Vascular Injury By Delayed Treatment With Captopril, Robert C. Molthen, Qingping Wu, Brian L. Fish, John E. Moulder, Elizabeth R. Jacobs, Meetha M. Medhora

Biomedical Engineering Faculty Research and Publications

Background and Objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage.

Methods: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2 months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2 weeks after radiation exposure, with …

Exp-Sa: Explosives Tracking: A Microsystem For Detection Of Bacterial Endospores As Self-Replicating Nucleic Acid Taggants, Paul J. Millard, Mauricio Pereira Da Cunha, John T. Singer

University of Maine Office of Research Administration: Grant Reports

This proposal presents an integrated research and educational plan directed toward the production, detection, and identification of bacterial endospore taggants for explosive tracking. While the most immediate application of the research is related to stemming the activities of bioterrorists, the anticipated fundamental advances in bioengineering and sensor science and engineering will have significant societal relevance to other applications, including first-responder activities, healthcare, food safety, and pollution avoidance and mitigation.

Intellectual Merit
The investigators propose to combine bioengineering of Bacillus stearothermophilus endospores with microdevices for sample processing and taggant identification. A surface acoustic wave (SAW) microdroplet mixing/transport/incubator system will be coupled …

Functional Classification Of Skeletal Muscle Networks. Ii. Applications To Pathophysiology, Yu Wang, Jack Winters, Shankar Subramaniam

Biomedical Engineering Faculty Research and Publications

In our preceding companion paper (Wang Y, Winters J, Subramaniam S. J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms …

Easily Implantable And Stable Nail-Fastener For Skeletal Fixation And Method, Patrick Atkinson, David Lecronier

Mechanical Engineering Patents

An intramedullary nail (20) for insertion into the medullary canal (26) in a bone (24) surrounded by the cortex (28) and defines a bore (34) extending transverse to the intramedullary nail (20). A threaded fastener (22) extends along a fastener axis (A) and has a compression portion (48) having a compression portion diameter (DCP), and a threaded portion (50) having a threaded portion diameter (DTP) extending through a near cortex hole (40) and a far cortex hole (42), both holes (40, 42) radially overlapping the bore (34) and the threaded portion diameter (DTP) threadedly engaging the bore (34). A compression …

Impairments In Sensorimotor Control During Pursuit And Compensatory Tracking In Individuals With Multiple Sclerosis, Scott A. Beardsley, Heenan M., Robert A. Scheidt, D. Woo, J. Bobholz

Biomedical Engineering Faculty Research and Publications

No abstract provided.