Biomedical Engineering and Bioengineering Commons^™

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction In Tauopathy, Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David K. Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren Iii, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging …

Electrical Double Layer In Nanopores For Detection And Identification Of Molecules And Submolecular Units, Guigen Zhang, Samuel Bearden

Biomedical Engineering Faculty Patents

Systems for detecting analytes in electrical double layer nanopore devices and methods of use are provided.

In Vivo Optical Metabolic Imaging Of Long-Chain Fatty Acid Uptake In Orthotopic Models Of Triple-Negative Breast Cancer, Megan C. Madonna, Joy E. Duer, Joyce V. Lee, Jeremy Williams, Baris Avsaroglu, Caigang Zhu, Riley Deutsch, Roujia Wang, Brian T. Crouch, Matthew D. Hirschey, Andrei Goga, Nirmala Ramanujam

Biomedical Engineering Faculty Publications

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, …

Analysis Of Graded Sensorimotor Rhythms For Brain-Computer Interface Applications, Chase Allen Haddix

Theses and Dissertations--Biomedical Engineering

The emerging field of neural engineering is tasked with applying engineering principles towards understanding neuroscience. A by-product of such a venture has been the development of a class of assistive devices known as brain-computer interfaces (BCIs) which link brain activity to actions performed by external devices. One application of this technology is in the rehabilitative sector for individuals with neuromuscular diseases and disorders. Despite tremendous efforts in the last few decades, a reliable signal that reflects fine motor control has yet to be adequately investigated. This gap in knowledge has limited the potential of BCIs to restore movement and communication. …

Scalable Approaches For Auditing The Completeness Of Biomedical Ontologies, Fengbo Zheng

Theses and Dissertations--Computer Science

An ontology provides a formalized representation of knowledge within a domain. In biomedicine, ontologies have been widely used in modern biomedical applications to enable semantic interoperability and facilitate data exchange. Given the important roles that biomedical ontologies play, quality issues such as incompleteness, if not addressed, can affect the quality of downstream ontology-driven applications. However, biomedical ontologies often have large sizes and complex structures. Thus, it is infeasible to uncover potential quality issues through manual effort. In this dissertation, we introduce automated and scalable approaches for auditing the completeness of biomedical ontologies. We mainly focus on two incompleteness issues -- …

Characterization Of Modulation And Coherence In Sensorimotor Rhythms Using Different Electroencephalographic Signal Derivations, Stephen Dundon

Theses and Dissertations--Biomedical Engineering

Electroencephalography (EEG) is a widely used technique for monitoring and analyzing brain activity in experimental, diagnostic, and therapeutic applications. Since EEG is sensitive to noise and artefact sources, referential signals at different locations can be combined in different ways to improve signal quality and better localize cortical activity. Four signal derivations were compared against referential EEG in terms of their ability to measure the alpha rhythm modulation (or reactivity) and spatial coherence associated with an eye closure task: a common average reference (CAR), a local average reference (LAR), a large Laplacian (LL), and a focal Laplacian (FL) estimated using a …

Work-Related Changes In The Trunk Stiffness Of Nursing Personnel, Clare Tyler

Theses and Dissertations--Biomedical Engineering

Low back pain (LBP) is a significant issue related to spinal stability and, therefore, to trunk stiffness. Due to the nature of their work, nursing personnel are exposed to potential risk factors for LBP, such as lifting and trunk flexion, which have been reported in the literature to lead to decreases in trunk stiffness. Consequently, the purpose of this study was to investigate potential occupational effects on the trunk stiffness in nursing personnel. Twenty-four nursing personnel participated in this study and completed two sessions (pre-shift and post-shift) during which two passive flexion tests (with and without an ~7.5-lb load) were …

Novel Tools For Analysis Of Disordered Sleep And Motor Behavior In Preclinical Models Of Disease, Dillon M. Huffman

Theses and Dissertations--Biomedical Engineering

Subtle changes in sleep architecture can accompany and be symptomatic of various diseases or disorders. Understanding the complex interactions between sleep and health requires the ability to characterize sleep, probe its underlying mechanisms through perturbation, and quantify dependent physiological outcomes. Rodent models have come to be accepted as a valuable tool for preclinical investigations. However, experimental tools to accomplish such research typically rely on laborious methods that limit throughput and flexibility. Thus, research tools that minimize workload could be of great value to the research community and expedite investigation of the underlying mechanisms of sleep and further the development of …

Changes In Cardiovascular, Respiratory, And Neural Activity By Music: Effects Of Breathing Pathway On Feeling Emotions, Mohammad Javad Mollakazemi

Theses and Dissertations--Biomedical Engineering

Listening to music can induce emotional and physiological changes. Increasing recognition of the palliative effects of music has led to its use as an adjuvant therapeutic tool in the treatment of various diseases. It is also well known that autonomic nervous activities and some cardiorespiratory rhythms change in correspondence with music. However, less is known about how these effects triggered by music come about. Listening to music affects synchronization between electroencephalograms (EEGs) and cardiac rhythmic activity. This interaction between cardiac and electrical responses led us to investigate whether EEG segments synchronized to different portions of the cardiac cycle can better …

Facilitating Analysis Of Toxoplasma Gondii Bradyzoite Metabolic Activity Via Image Processing And Multivariate Logistic Regression For High Throughput Classification Of Mitochondrial Morphologies, Brooke Place

Theses and Dissertations--Biomedical Engineering

Approximately a third of the population worldwide is chronically infected by the parasite Toxoplasma gondii. During chronic infection the parasite resides within tissue cysts as the poorly understood bradyzoite form. Observation of these bradyzoites via microscopic imaging within tissue cyst purified from infected mouse brains has shown metabolic activity with heterogeneous replication potential. With fluorescence microscopy imaging targeting the parasite’s actively respiring mitochondria, the parasite’s metabolic state can be further investigated as the morphology of mitochondria can be associated with specific physiologic states. However, manually classifying mitochondrial morphologies from these images can be tedious and prone to error as …

Tailoring Texture, Microstructure, And Shape Memory Behavior Of Niti Alloys Fabricated By L-Pbf-Am, Sayed Ehsan Saghaian N.E.

Theses and Dissertations--Mechanical and Aerospace Engineering

Laser Powder Bed Fusion (L-PBF) is one of the most promising Additive Manufacturing (AM) methods to fabricate near net-shape metallic materials for a wide range of applications such as patient-specific medical devices, functionally graded materials, and complex structures. NiTi shape memory alloys (SMAs) are of great interest due to a combination of unique features, such as superelasticity, shape memory effect, high ductility, work output, corrosion resistance, and biocompatibility that could be employed in many applications in automotive, aerospace, and biomedical industries. Due to the difficulties with traditional machining and forming of NiTi components, the ability to fabricate complex parts, tailor …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Machine Learning Approach For Vigilance State Classification In Mice, Anik Muhury

Theses and Dissertations--Electrical and Computer Engineering

Sleep has a significant impact on cognitive abilities such as memory, reaction time, productivity, and creative thinking; however, there are many aspects of this important activity that are not clearly understood. Over the last century, researchers have developed technology and animal models to assist in the study of sleep. Manual sleep scoring is time consuming, reduces productivity, and is impacted by human scorer subjectivity. On the other hand, automatic sleep stage categorization can enhance consistency and reliability, aiding professionals in identifying sleep related health problems.

In recent times various studies reported significant achievements for automatic vigilance detection and overcome the …

Optimization Of Gelatin-Based Cellular Coating Of Msc For Myocardial Infarction Therapy, Kara Amelle Davis

Theses and Dissertations--Chemical and Materials Engineering

Cardiovascular disease remains the number one threat to American lives. During an acute myocardial infarction (AMI), blood flow is blocked and results in the formation of scar tissue. As the body’s immune system responds, inflammatory signaling causes an increase in both scar tissue size and the patient’s risk for further chronic heart failure. In order to reduce the risk of continued heart disease inflammatory signaling must be reduced. Stem cell therapies have the ability to alter the immune system’s pro-inflammatory signal. However, stem cell retention is limited due to blood flow shear. Gelatin methacrylate (GelMA) based coatings have been shown …

Compact Low-Cost Fiberless Diffuse Speckle Contrast Flow-Oximeter, Guoqiang Yu, Chong Huang, J. Todd Hastings

Biomedical Engineering Faculty Patents

A low-cost compact fiberless diffuse speckle contrast flow-meter includes a small laser diode and a 2-dimensional imaging device such as a charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS) for directly contacting the tissue and measuring a parameter such as blood flow in a deep/thick volume of tissue (up to 10 mm depth). The small laser diode is fixed at a certain distance (0 to 20 mm) from the imaging device and directly contacts the tissue. Light emitted from the laser diode penetrates through the tissue and reflects back to the imaging device without passing through any lenses …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady

Physiology Faculty Publications

Techniques available for micro- and nano-scale mechanical characterization have exploded in the last few decades. From further development of the scanning and transmission electron microscope, to the invention of atomic force microscopy, and advances in fluorescent imaging, there have been substantial gains in technologies that enable the study of small materials. Conpokal is a portmanteau that combines confocal microscopy with atomic force microscopy (AFM), where a probe "pokes" the surface. Although each technique is extremely effective for the qualitative and/or quantitative image collection on their own, Conpokal provides the capability to test with blended fluorescence imaging and mechanical characterization. Designed …

Changes In Lumbo-Pelvic Coordination Of Individuals With And Without Low Back Pain When Wearing A Hip Orthosis, Matthew T. Ballard, Colin Drury, Babak Bazrgari

Biomedical Engineering Faculty Publications

Individuals with low back pain demonstrate an abnormal lumbo-pelvic coordination compared to back-healthy individuals. This abnormal coordination presents itself as a reduction in lumbar contributions and an increase in pelvic rotations during a trunk forward bending and backward return task. This study investigated the ability of a hip orthosis in correcting such an abnormal lumbo-pelvic coordination by restricting pelvic rotation and, hence increasing lumbar contributions. The effects of the hip orthosis on the lumbo-pelvic coordination were investigated in 20 low back pain patients and 20 asymptomatic controls. The orthosis reduced pelvic rotation by 12.7° and increased lumbar contributions by 11%. …

Β-Amyloid And Tau Drive Early Alzheimer's Disease Decline While Glucose Hypometabolism Drives Late Decline, Tyler C. Hammond, Xin Xing, Chris Wang, David Ma, Kwangsik Nho, Paul K. Crane, Fanny Elahi, David A. Ziegler, Gongbo Liang, Qiang Cheng, Lucille M. Yanckello, Nathan Jacobs, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer’s disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer’s Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of Aβ …

A Comparative Study Of Sleep And Diurnal Patterns In House Mouse (Mus Musculus) And Spiny Mouse (Acomys Cahirinus), Chanung Wang, Lauren E. Guerriero, Dillon M. Huffman, Asma'a A. Ajwad, Trae C. Brooks, Sridhar Sunderam, Ashley W. Seifert, Bruce F. O'Hara

Biomedical Engineering Faculty Publications

Most published sleep studies use three species: human, house mouse, or Norway rat. The degree to which data from these species captures variability in mammalian sleep remains unclear. To gain insight into mammalian sleep diversity, we examined sleep architecture in the spiny basal murid rodent Acomys cahirinus. First, we used a piezoelectric system validated for Mus musculus to monitor sleep in both species. We also included wild M. musculus to control for alterations generated by laboratory-reared conditions for M. musculus. Using this comparative framework, we found that A. cahirinus, lab M. musculus, and wild M. musculus were …

Small Molecule Drug Release Form In Situ Forming Degradable Scaffolds Incorporating Hydrogels And Bioceramic Microparticles, David A. Puleo, Todd A. Milbrandt, J. Zach Hilt, Paul Fisher, Vishwas Talwalkar

Biomedical Engineering Faculty Patents

The present invention relates to an injectable system combining a hydrogel, a bioceramic and a degradable matrix that provides for sustained drug delivery and structural support to recovering tissue, such as bone and the periodontium.

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Barn-Raising On The Digital Frontier: The L.A.U.N.C.H. Collaborative, Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie Mccomsey, Alexandra Hubenko, Bin Huang, Corey Baker, Don Norman

Journal of Appalachian Health

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches—or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic—are becoming an indispensable tool in medicine to overcome the obstacle of distance.

Early Acid/Base And Electrolyte Changes In Permanent Middle Cerebral Artery Occlusion: Aged Male And Female Rats, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Sarah J. Goodwin, David Powell, Doug Lukins, Justin F. Fraser, Keith R. Pennypacker

Neurosurgery Faculty Publications

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model.

METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and …

Atv Dynamics And Pediatric Rider Safety, James T. Auxier Ii

Theses and Dissertations--Biomedical Engineering

It has been observed through numerous academic and governmental agency studies that pediatric all-terrain vehicle ridership carries significant risk of injury and death. While no doubt valuable to safety, the post-hoc approach employed in these studies does little to explain the why and how behind the risk factors. Furthermore, there has been no prolonged, widespread, organized, and concerted effort to reconstruct and catalog the details and causes of the large (20,000+) number of ATV-related injuries that occur each year as has been done for road-based motor vehicle accidents. This dissertation takes the opposite approach from a meta-analysis and instead examines …

Assessment Of White Matter Hyperintensity, Cerebral Blood Flow, And Cerebral Oxygenation In Older Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani

Theses and Dissertations--Biomedical Engineering

Objective: Cerebrovascular disease (CVD) is the fifth most common cause of mortality in the United States. Diagnosis of CVD at an early stage is critical for optimal intervention designed to prevent ongoing and future brain injury. CVD is commonly associated with abnormalities of the cerebral microvasculature leading to tissue dysfunction, neuronal injury and death, and resultant clinical symptoms, which in turn, further impacts cerebral autoregulation (CA). This series of studies aims to test the hypothesis that white matter hyperintensities (WMH) and cerebral hemodynamics (quantified by magnetic resonance imaging (MRI) and an by innovative hybrid near-infrared diffuse optical instrument) can be …

Effects Of A Hip Orthosis On Lumbopelvic Coordination In Individuals With And Without Low Back Pain, Colin Drury

Theses and Dissertations--Biomedical Engineering

Individuals with low back pain (LBP) demonstrate an abnormal lumbopelvic coordination compared to back-healthy individuals. This abnormal coordination presents itself as a reduction in lumbar contribution and an increase in pelvic contribution to trunk motion. This study investigated the ability of a hip orthosis to correct such an abnormal lumbo-pelvic coordination by restricting pelvic rotation and, as a result, increasing lumbar contributions. The effects of the hip orthosis on the magnitude and timing characteristics of lumbopelvic coordination were investigated in 20 patients with LBP and 20 asymptomatic controls. The orthosis significantly increased lumbar contributions by 11%, 5.42%, 4.84%, and 4.89% …

High Frequency Oscillations In The Epileptic Brain: Accurate Detection, Effect Of Vigilance State, And Sample Size Considerations, Amir Fared Partu Al-Bakri

Theses and Dissertations--Biomedical Engineering

About a third of all epilepsy patients may experience seizures that are resistant to medication. Surgical resection may be an option for some of these patients, but localization of the epileptogenic zone is difficult and expensive. For this process, the seizures must be observed and recorded in a clinical setting over several days. High-frequency oscillations (HFOs) have emerged as a possible biomarker for predicting the epileptogenic zone from a brief interictal recording of brain electrical activity without having to wait for seizures. The broad objective of this dissertation is to devise methods and criteria for accurate detection, sampling and localization …

Work Related Diurnal Changes In Trunk Mechanical Behavior, Maeve Mcdonald

Theses and Dissertations--Biomedical Engineering

The objectives of this study were to analyze effects of day-long exposure to LBP risk factors on lumbo-pelvic coordination (LPC) in nursing occupations and to verify if physical activity level affects diurnal work-related changes in LPC. Thirty-three nurses were recruited into three groups based on workplace physical demands and each completed two data collection sessions, one before and one after their 8-12 hour work shift. Participants completed several stationary trunk forward-bending/backward-return exercises at self-selected “fast” and “slow” rotational speeds, and while holding a 15 lbs. load. Kinematic data collected during these exercises were then used to characterize the timing and …

Noncontact Multiscale Diffuse Optical Imaging Of Deep Tissue Hemodynamics In Animals And Humans, Siavash Mazdeyasna

Theses and Dissertations--Biomedical Engineering

Blood flow (BF) impacts the delivery of oxygen and nutrients to tissues and the removal of metabolic byproducts from tissues. Imaging of BF distributions helps characterize many diseases associated with tissue hypoxia/ischemia. The purpose of this study was to develop and validate a novel, noninvasive, noncontact, high-density camera-based speckle contrast diffuse correlation tomography (scDCT) device for use in both animal and human studies. The scDCT uses a galvo-mirror to remotely deliver the focused point near-infrared light to source positions and a sensitive 2D camera to quantify spatial diffuse speckle fluctuations, resulting from the movement of red blood cells in deep …