Biomedical Engineering and Bioengineering Commons^™

Finite Element Simulation And Additive Manufacturing Of Stiffness-Matched Niti Fixation Hardware For Mandibular Reconstruction Surgery, Ahmadreza Jahadakbar, Narges Shayesteh Moghaddam, Amirhesam Amerinatanzi, David Dean, Haluk E. Karaca, Mohammad Elahinia

Mechanical Engineering Faculty Publications

Process parameters and post-processing heat treatment techniques have been developed to produce both shape memory and superelastic NiTi using Additive Manufacturing. By introducing engineered porosity, the stiffness of NiTi can be tuned to the level closely matching cortical bone. Using additively manufactured porous superelastic NiTi, we have proposed the use of patient-specific, stiffness-matched fixation hardware, for mandible skeletal reconstructive surgery. Currently, Ti-6Al-4V is the most commonly used material for skeletal fixation devices. Although this material offers more than sufficient strength for immobilization during the bone healing process, the high stiffness of Ti-6Al-4V implants can cause stress shielding. In this paper, …

Polymeric Prodrug, David A. Puleo, Thomas D. Dziubla, Theodora Asafo-Adjei

Biomedical Engineering Faculty Patents

The presently-disclosed subject matter includes compounds that comprise an initiator and an active agent that is covalently bonded to the initiator through a ring-opening polymerization process, an atom-transfer radical polymerization process, a Michael addition reaction, or a ring-opening metathesis polymerization process. In some embodiments the active agent includes simvastatin. The presently-disclosed subject matter also includes methods for making the compositions and methods for using the compositions to treat tissue wounds.

An Interactive Videogame Designed To Improve Respiratory Navigator Efficiency In Children Undergoing Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Jonathan D. Grabau, Kristin N. Andres, Moriel H. Vandsburger, David K. Powell, Vincent L. Sorrell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Advanced cardiovascular magnetic resonance (CMR) acquisitions often require long scan durations that necessitate respiratory navigator gating. The tradeoff of navigator gating is reduced scan efficiency, particularly when the patient’s breathing patterns are inconsistent, as is commonly seen in children. We hypothesized that engaging pediatric participants with a navigator-controlled videogame to help control breathing patterns would improve navigator efficiency and maintain image quality.

Methods: We developed custom software that processed the Siemens respiratory navigator image in real-time during CMR and represented diaphragm position using a cartoon avatar, which was projected to the participant in the scanner as visual feedback. The …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Low-Cost Compact Diffuse Speckle Contrast Flowmeter Using Small Laser Diode And Bare Charge-Coupled-Device, Chong Huang, Myeongsu Seong, Joshua Paul Morgan, Siavash Mazdeyasna, Jae Gwan Kim, Jeffrey Todd Hastings, Guoqiang Yu

Biomedical Engineering Faculty Publications

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼8  mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland–Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5% ± 2.2% (94.4% to 100.0%) in phantom experiments and 92.8% …

Cardiac Remodeling And Dysfunction In Childhood Obesity: A Cardiovascular Magnetic Resonance Study, Linyuan Jing, Cassi M. Binkley, Jonathan D. Suever, Nivedita Umasankar, Christopher M. Haggerty, Jennifer Rich, Christopher D. Nevius, Gregory J. Wehner, Sean M. Hamlet, David K. Powell, Aurelia Radulescu, H. Lester Kirchner, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

Background: Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.

Methods and results: Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index …

Mri Signal Intensity Differentiation Of Brainstem Encephalitis Induced By Enterovirus 71: A Classification Approach For Acute And Convalescence Stages, Hongwu Zeng, Wenxian Huang, Feiqiu Wen, Yonker Wang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background: The objective of this study is to assess standardized histograms of signal intensities of T1 signal and T2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with Enterovirus 71 related brainstem encephalitis (BE), and with respect to (3) healthy normal.

Methods: Our subjects were hospitalized between March 2010 and October 2012, and underwent pre- and post-contrast MRI studies. The research question to be answered is whether the comparison of the MRI image intensity histograms and relevant statistical quantification can add new knowledge to the diagnosis of BE patients. So, both …

Segway: A Simple Framework For Unsupervised Sleep Segmentation In Experimental Eeg Recordings, Farid Yaghouby, Sridhar Sunderam

Biomedical Engineering Faculty Publications

Sleep analysis in animal models typically involves recording an electroencephalogram (EEG) and electromyogram (EMG) and scoring vigilance state in brief epochs of data as Wake, REM (rapid eye movement sleep) or NREM (non-REM) either manually or using a computer algorithm. Computerized methods usually estimate features from each epoch like the spectral power associated with distinctive cortical rhythms and dissect the feature space into regions associated with different states by applying thresholds, or by using supervised/unsupervised statistical classifiers; but there are some factors to consider when using them:

• Most classifiers require scored sample data, elaborate heuristics or computational steps not easily …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Supernormal Conduction And Suppression Of Spatially Discordant Alternans Of Cardiac Action Potentials, Linyuan Jing, Anuj Agarwal, Abhijit R. Patwardhan

Biomedical Engineering Faculty Publications

Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate …

Biventricular Finite Element Modeling And Quantification Of 3d Langragian Strains And Torsion Using Dense Mri, Zhanqiu Liu

Theses and Dissertations--Mechanical Engineering

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in …

Analysis Of Vocal Fold Kinematics Using High Speed Video, Harikrishnan Unnikrishnan

Theses and Dissertations--Electrical and Computer Engineering

Vocal folds are the twin in-folding of the mucous membrane stretched horizontally across the larynx. They vibrate modulating the constant air flow initiated from the lungs. The pulsating pressure wave blowing through the glottis is thus the source for voiced speech production. Study of vocal fold dynamics during voicing are critical for the treatment of voice pathologies. Since the vocal folds move at 100 - 350 cycles per second, their visual inspection is currently done by strobosocopy which merges information from multiple cycles to present an apparent motion. High Speed Digital Laryngeal Imaging(HSDLI) with a temporal resolution of up to …

Reference Point Indentation Of Human Trabecular Bone Treated With Bisphosphonates For Varying Durations, Drew Jones

Theses and Dissertations--Biomedical Engineering

Reference point indentation (RPI), a novel form of micro-indentation, quantifies RPI material parameters which correlate with modulus, yield stress, strength, or toughness. Information linking bisphosphonate treatment length with the material properties of osteoporotic trabecular bone is needed to improve patient treatment. The objectives of this study were to: 1) determine if RPI can be used to successfully evaluate human trabecular bone and if so, determine an optimized test method for using RPI on trabecular bone, and 2) use this method to determine if any RPI parameters are related to the duration of bisphosphonate treatment.

Indentation using a 4 N applied …

Closed-Loop Afferent Nerve Electrical Stimulation For Rehabilitation Of Hand Function In Subjects With Incomplete Spinal Cord Injury, Christopher J. Schildt

Theses and Dissertations--Biomedical Engineering

Peripheral nerve stimulation (PNS) is commonly used to promote use-dependent cortical plasticity for rehabilitation of motor function in spinal cord injury. Pairing transcranial magnetic stimulation (TMS) with PNS has been shown to increase motor evoked potentials most when the two stimuli are timed to arrive in the cortex simultaneously. This suggests that a mechanism of timing-dependent plasticity (TDP) may be a more effective method of promoting motor rehabilitation. The following thesis is the result of applying a brain-computer interface to apply PNS in closed-loop simultaneously to movement intention onset as measured by EEG of the sensorimotor cortex to test whether …

Recent Advances In Optical Spectroscopic And Imaging Methods For Medicine And Biology, Yu Shang, Zhiyu Qian, Rickson C. Mesquita, Mathieu Dehaes

Biomedical Engineering Faculty Publications

No abstract provided.

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Synthesis And Characterization Of Curcumin Polymer For Application In Radiation Induced Lung Damage, Mark C. Bailey

Theses and Dissertations--Chemical and Materials Engineering

Radiotherapy is used as a primary treatment for many cancers, including lung cancer. Although radiotherapy has proven to be an effective cancer treatment, its use is heavily limited due to the peripheral toxicity to healthy tissue. In this work, the antioxidant, curcumin, was tested as a radioprotectant to reduce radiation damage to healthy cells. Curcumin has been limited in use due to its poor bioavailability. In order to avoid problems associated with free curcumin delivery, curcumin poly(beta-amino ester) (CPBAE) was synthesized.

The first study investigated the in vitro radioprotection effect of curcumin in HUVEC dosed with gamma radiation. Cells treated …

Alterations In Active And Passive Behavior Of Lower Back Tissues Following Six Sessions Of High Velocity Low Amplitude Spinal Manipulative Therapy For Healthy Participants, Emily C. Croft

Theses and Dissertations--Biomedical Engineering

Non-specific low back pain (LBP) is a major health problem affecting a substantial portion of the population. The current treatments offered for non-specific LBP are oftentimes unsuccessful because the acting mechanism(s) of most treatment options are unknown. Obtaining a better understanding about the acting mechanism behind existing treatment options is, therefore, essential for the improvement of non-specific LBP treatment and management. The objective of this study was to gain a more comprehensive understanding about the acting mechanism of high velocity low amplitude spinal manipulative therapy, specifically the impact that high velocity low amplitude spinal manipulative therapy may have on the …

Detection Of Electrical Alternans In Ventricular Depolarization Phase Of Human Electrocardiogram, David R. Wasemiller

Theses and Dissertations--Biomedical Engineering

T-wave Alternans (TWA) in an electrocardiogram (ECG) has received considerable interest as a potential predictor of sudden cardiac death (SCD). However, large clinical trials have shown that while TWA has a very high negative predictive value, its positive predictive value is poor. Results of previous studies suggest that arrhythmia onset can be affected by the phase relationship of alternans of the depolarization and repolarization phase of the action potentials of the ventricles. To assess this relationship, one would first need to establish that depolarization alternans can be detected and then develop methods to determine its relationship with repolarization alternans, which …

The Rheological Impact Of Cell Activation On The Flow Behavior Of Neutrophils, Nolan M. Horrall

Theses and Dissertations--Biomedical Engineering

Previously, it was reported that the morphological changes (pseudopod projection) that circulating neutrophils adopt due to cell activation raises peripheral vascular resistance by disrupting microvascular rheology. Studies utilized murine muscle preparations to link neutrophil pseudopod formation to cell activation and a viscous impact on hemodynamic resistance. But because of the complexity associated with the organization of the vasculature and microvasculature in tissues, it was unclear whether the effects of neutrophil activation on hemodynamic resistance were associated with the macro-/micro- circulation. This research describes an in vitro analysis using viscometry and microvascular network mimics (microporous membranes) to assess the rheological impact …

The Influence Of Cholesterol-Related Membrane Fluidity On The Shear Stress Control Of Neutrophil Adhesion And Its Implications In Hypercholesterolemia, Michael L. Akenhead

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a significant risk factor in the development of cardiovascular disease and is associated with chronic leukocyte adhesion in the microvasculature. While the underlying mechanisms behind this have yet to be determined, it may be possible that hypercholesterolemia impairs the fluid shear stress (FSS) inactivation of neutrophils through the rigidifying effect of cholesterol on membrane fluidity. FSS restricts surface expression of CD18 integrins through cathepsin B (ctsB) proteolysis, which minimizes neutrophil adhesivity. If hypercholesterolemia blocks FSS mechanotransduction, then the inhibition of CD18 cleavage may link pathologic blood cholesterol elevations with dysregulated neutrophil adhesion. We hypothesized that elevated cholesterol contributes …

Three-Dimensional Endothelial Spheroid-Based Investigation Of Pressure-Sensitive Sprout Formation, Min Song

Theses and Dissertations--Biomedical Engineering

This study explored hydrostatic pressure as a mechanobiological parameter to control in vitro endothelial cell tubulogenesis in 3-D hydrogels as a model microvascular tissue engineering approach. For this purpose, the present investigation used an endothelial spheroid model, which we believe is an adaptable microvascularization strategy for many tissue engineering construct designs. We also aimed to identify the operating magnitudes and exposure times for hydrostatic pressure-sensitive sprout formation as well as verify the involvement of VEGFR-3 signaling. For this purpose, we used a custom-designed pressure system and a 3-D endothelial cell spheroid model of sprouting tubulogenesis. We report that an exposure …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Synthesis And Characterization Of Antioxidant Conjugated Poly(Βeta-Amino Ester) Micro/Nanogels For The Suppression Of Oxidative Stress, Prachi Gupta

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS), which can result in the growth arrest of cells followed by cell disintegration or necrosis. A number of small molecule antioxidants (e.g. curcumin, quercetin and resveratrol) are capable of directly scavenging ROS, thereby short-circuiting the self-propagating oxidative stress state. However, poor solubility and rapid 1^st pass metabolism results in overall low bioavailability and acts as a barrier for its use as a drug to suppress oxidative stress efficiently.

To overcome this limitation, these small molecule antioxidants were covalently conjugated into poly(β-amino ester) (PβAE) …

Diffusion-Mediated Deposition Of Proteins, Ruiqian Zhan

Theses and Dissertations--Mechanical Engineering

Gradients of proteins play a prominent role in many biological processes, from development of multicellular organisms to chemical signaling in the immune system. Deposition of surface gradients is a way to permanently modifying a surface’s properties, resulting in the creation of novel materials which have widespread applications in biologically relevant fields, such as directed cell growth, production of biocompatible implantable materials, and creation of functional biosensors. These types of surfaces can also be used as an ex vivo tool to help understand many biological processes by mimicking the environment in gradient-related phenomena in a controllable way. However, despite the large …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Automated Solid-Substrate Cultivation Of The Anaerobic Bacterium Clostridium Thermocellum, Mathew J. Ruwaya

Theses and Dissertations--Biosystems and Agricultural Engineering

The organism Clostridium thermocellum grows on cellulosic substrates and produces ethanol, acetate, lactate, formic acid, and CO₂. The organic acids produced alter the growth environment in which the bacteria grows and ultimately inhibit bacterial growth. One method which has been used successfully to maintain the system at acceptable growth conditions is to intermittently flush out the spent media and metabolic products and replace with new fermentation media. Our goal was to design and build an automated system that will automatically flush the spent media from the growing culture and resupply new media without manual intervention. An automated control …