Biomedical Engineering and Bioengineering Commons^™

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Noncontact Speckle Contrast Diffuse Correlation Tomography Of Blood Flow Distributions In Tissues With Arbitrary Geometries, Siavash Mazdeyasna, Chong Huang, Mingjun Zhao, Nneamaka B. Agochukwu, Ahmed A. Bahrani, Lesley Wong, Guoqiang Yu

Biomedical Engineering Faculty Publications

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the …

Comparison Of Left Ventricular Strains And Torsion Derived From Feature Tracking And Dense Cmr, Gregory J. Wehner, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Jing Chen, Sean M. Hamlet, Jared A. Feindt, Walter Dimitri Mojsejenko, Mark A. Fogel, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Cardiovascular magnetic resonance (CMR) feature tracking is increasingly used to quantify cardiac mechanics from cine CMR imaging, although validation against reference standard techniques has been limited. Furthermore, studies have suggested that commonly-derived metrics, such as peak global strain (reported in 63% of feature tracking studies), can be quantified using contours from just two frames – end-diastole (ED) and end-systole (ES) – without requiring tracking software. We hypothesized that mechanics derived from feature tracking would not agree with those derived from a reference standard (displacement-encoding with stimulated echoes (DENSE) imaging), and that peak strain from feature tracking would agree with …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

Artificial Gravity As A Countermeasure To The Cardiovascular Deconditioning Of Spaceflight: Gender Perspectives, Joyce M. Evans, Charles F. Knapp, Nandu Goswami

Biomedical Engineering Faculty Publications

Space flight-induced physiological deconditioning resulting from decreased gravitational input, decreased plasma volume, and disruption of regulatory mechanisms is a significant problem in returning astronauts as well as in normal aging. Here we review effects of a promising countermeasure on cardiovascular systems of healthy men and women undergoing Earth-based models of space-flight. This countermeasure is produced by a centrifuge and called artificial gravity (AG). Numerous studies have determined that AG improves orthostatic tolerance (as assessed by various protocols) of healthy ambulatory men, of men deconditioned by bed rest or by immersion (both wet and dry) and, in one case, following spaceflight. …

Elucidating The Mechanisms Of Two Unique Phenomena Governed By Particle-Particle Interaction Under Dep: Tumbling Motion Of Pearl Chains And Alignment Of Ellipsoidal Particles, Yu Zhao, Jozef Brcka, Jacques Faguet, Guigen Zhang

Biomedical Engineering Faculty Publications

Particle-particle interaction plays a crucial role in determining the movement and alignment of particles under dielectrophoresis (DEP). Previous research efforts focus on studying the mechanism governing the alignment of spherical particles with similar sizes in a static condition. Different approaches have been developed to simulate the alignment process of a given number of particles from several up to thousands depending on the applicability of the approaches. However, restricted by the simplification of electric field distribution and use of identical spherical particles, not much new understanding has been gained apart from the most common phenomenon of pearl chain formation. To enhance …

Cortical Statistical Correlation Tomography Of Eeg Resting State Networks, Chuang Li, Han Yuan, Guofa Shou, Yoon-Hee Cha, Sridhar Sunderam, Walter Besio, Lei Ding

Biomedical Engineering Faculty Publications

Resting state networks (RSNs) have been found in human brains during awake resting states. RSNs are composed of spatially distributed regions in which spontaneous activity fluctuations are temporally and dynamically correlated. A new computational framework for reconstructing RSNs with human EEG data has been developed in the present study. The proposed framework utilizes independent component analysis (ICA) on short-time Fourier transformed inverse source maps imaged from EEG data and statistical correlation analysis to generate cortical tomography of electrophysiological RSNs. The proposed framework was evaluated on three sets of resting-state EEG data obtained in the comparison of two conditions: (1) healthy …

Renal Granulomatosis Post Intravesical Bacillus Calmette-Guerin Therapy For Non-Muscle-Invasive Bladder Cancer, Karen Tran-Harding, Rashmi T. Nair, Halemane S. Ganesh

Radiology Faculty Publications

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in < 5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

Walking Speed Differentially Alters Spinal Loads In Persons With Traumatic Lower Limb Amputation, Brad D. Hendershot, Iman Shojaei, Julian C. Acasio, Christopher L. Dearth, Babak Bazrgari

Biomedical Engineering Faculty Publications

Persons with lower limb amputation (LLA) perceive altered motions of the trunk/pelvis during activities of daily living as contributing factors for low back pain. When walking (at a singular speed), larger trunk motions among persons with vs. without LLA are associated with larger spinal loads; however, modulating walking speed is necessary in daily life and thus understanding the influences of walking speed on spinal loads in persons with LLA is of particular interest here. Three-dimensional trunk-pelvic kinematics, collected during level-ground walking at self-selected (SSW) and two controlled speeds (~1.0 and ~1.4 m/s), were obtained for seventy-eight participants: 26 with transfemoral …

Mechanical Demands On The Lower Back In Patients With Non-Chronic Low Back Pain During A Symmetric Lowering And Lifting Task, Iman Shojaei, Elizabeth G. Salt, Quenten L. Hooker, Babak Bazrgari

Biomedical Engineering Faculty Publications

There is limited information in the literature related to the lower back loading in patients with LBP, particularly those with non-chronic LBP. Toward addressing such a research gap, a case-control study was conducted to explore the differences in lower back mechanical loads between a group of females (n=19) with non-chronic, non-specific LBP and a group of asymptomatic females (n=19). The differences in lower back mechanical loads were determined when participants completed one symmetric lowering and lifting of a 4.5 kg load at their preferred cadence. The axial, shearing, and moment components of task demand at the time of peak moment …

A Model-Based Approach For Estimation Of Changes In Lumbar Segmental Kinematics Associated With Alterations In Trunk Muscle Forces, Iman Shojaei, Navid Arjmand, Judith R. Meakin, Babak Bazrgari

Biomedical Engineering Faculty Publications

The kinematics information from imaging, if combined with optimization-based biomechanical models, may provide a unique platform for personalized assessment of trunk muscle forces (TMFs). Such a method, however, is feasible only if differences in lumbar spine kinematics due to differences in TMFs can be captured by the current imaging techniques. A finite element model of the spine within an optimization procedure was used to estimate segmental kinematics of lumbar spine associated with five different sets of TMFs. Each set of TMFs was associated with a hypothetical trunk neuromuscular strategy that optimized one aspect of lower back biomechanics. For each set …

Bilayered Calcium Sulfate/Calcium Phosphate Space-Making Composites With Multiple Drug Delivery Capabilities, David A. Puleo, Bryan R. Orellana, Mike Mcquinn

Biomedical Engineering Faculty Patents

The present invention provides for bilayered composites that provide for sustained drug delivery and support to recovering tissue(s) and areas surrounding, such as with bone tissue. The two layers degrade at separate rates, thereby providing sustained mechanical support and tailored drug delivery.

Muscle Activity During Maximal Isometric Forearm Rotation Using A Power Grip, Joseph Scott Bader, Michael R. Boland, Desney Greybe, Arthur J. Nitz, Timothy L. Uhl, David A. Pienkowski

Biomedical Engineering Faculty Publications

This study aimed to provide quantitative activation data for muscles of the forearm during pronation and supination while using a power grip. Electromyographic data was collected from 15 forearm muscles in 11 subjects while they performed maximal isometric pronating and supinating efforts in nine positions of forearm rotation. Biceps brachii was the only muscle with substantial activation in only one effort direction. It was significantly more active when supinating (µ = 52.1%, SD = 17.5%) than pronating (µ = 5.1%, SD = 4.8%, p < .001). All other muscles showed considerable muscle activity during both pronation and supination. Brachioradialis, flexor carpi radialis, palmaris longus, pronator quadratus and pronator teres were significantly more active when pronating the forearm. Abductor pollicis longus and biceps brachii were significantly more active when supinating. This data highlights the importance of including muscles additional to the primary forearm rotators in a biomechanical analysis of forearm rotation. Doing so will further our understanding of forearm function and lead to the improved treatment of forearm fractures, trauma-induced muscle dysfunction and joint replacements.

Noncontact Three-Dimensional Diffuse Optical Imaging Of Deep Tissue Blood Flow Distribution, Guoqiang Yu, Yu Lin, Chong Huang

Biomedical Engineering Faculty Patents

The present invention provides for three-dimensional reflectance diffuse optical imaging of deep tissue blood flow distribution that removes the need for probe-tissue contact, thereby allowing for such technology to be applied to sensitive, vulnerable, damaged, or reconstructive tissue. The systems utilize noncontact application and detection of near-infrared light through optical lens and detection through a linear array or two-dimensional array of avalanche photodiodes or a two-dimensional array of detectors provided by charge-coupled-device (CCD). Both further feature a finite-element-method (FEM) based facilitation to provide for three-dimensional flow image reconstruction in deep tissues with arbitrary geometries.

Comparison Of Eosin And Fluorescein Conjugates For The Photoinitiation Of Cell-Compatible Polymer Coatings, Jacob L. Lilly, Anuhya Gottipati, Calvin F. Cahall, Mohamed Agoub, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

Targeted photopolymerization is the basis for multiple diagnostic and cell encapsulation technologies. While eosin is used in conjunction with tertiary amines as a water-soluble photoinitiation system, eosin is not widely sold as a conjugate with antibodies and other targeting biomolecules. Here we evaluate the utility of fluorescein-labeled bioconjugates to photopolymerize targeted coatings on live cells. We show that although fluorescein conjugates absorb approximately 50% less light energy than eosin in matched photopolymerization experiments using a 530 nm LED lamp, appreciable polymer thicknesses can still be formed in cell compatible environments with fluorescein photosensitization. At low photoinitiator density, eosin allows more …

Objectively Measuring Effects Of Electro-Acupuncture In Parkinsonian Rhesus Monkeys, Rui Zhang, Anders H. Andersen, Peter A. Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M. Gash, Richard Grondin, Zhiming Zhang

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson’s disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed …

Adrenergic Stimulation In Acute Hyperglycemia: Effects On Cellular And Tissue Level Murine Cardiac Electrophysiology, Sridevi Thyagarajan

Theses and Dissertations--Biomedical Engineering

Cardiovascular complications associated with elevated levels of glucose in the blood (Hyperglycemia, HG) is a growing health concern. HG is known to be associated with a variety of cardiovascular morbidities including higher incidence of electrical disturbances. Although effects of chronic HG have been widely investigated, electrophysiological effects of acute hyperglycemia are relatively less known. Further, hyperglycemic effects on adrenergic response is not widely investigated. We used excised ventricular tissues from mice to record trans-membrane potentials during a variety of pacing protocols to investigate cellular/tissue level electrophysiological effects of acute hyperglycemia and adrenergic stimulation (1µM Isoproterenol, a β-adrenergic agonist). A custom …

Effects Of Lumbar Spinal Fusion On Lumbopelvic Rhythm During Activities Of Daily Living, Cameron G. Slade

Theses and Dissertations--Biomedical Engineering

Abnormalities in lumbopelvic rhythm (LPR) play a role in occurrence/recurrence of low back pain (LBP). The LPR before spinal fusion surgery and its changes following the surgery are not understood. A repeated measure study was designed to investigate timing and magnitude aspects of LPR in a group of patients (n = 5) with LBP before and after a spinal fusion surgery. Participants completed a forward bending and backward return task at their preferred pace in the sagittal plane. The ranges of thoracic and pelvic rotations and lumbar flexion (as the magnitude aspects of LPR) as well as the mean absolute …

Effects Of Backpack Type On Kinematics Of The Lower Back During Walking And Jogging, Cazmon Suri

Theses and Dissertations--Biomedical Engineering

Heavy backpacks have been suggested to have a pathogenic role in experience of low back pain among children. We have conducted a repeated-measure study to investigate the backpack-induced changes in lumbo-pelvic coordination of forty gender-balanced college age students when they walked and jogged on a treadmill with two different types of backpacks: normal and ergonomically modified. The backpack-induced changes in lumbo-pelvic coordination were larger when carrying an ergonomically modified vs. a normal backpack as well as when jogging versus walking. The larger changes in lumbo-pelvic coordination when carrying an ergonomically modified backpack were likely due to kinematic restraints imposed by …

Interactive Clinical Event Pattern Mining And Visualization Using Insurance Claims Data, Zhenhui Piao

Theses and Dissertations--Computer Science

With exponential growth on a daily basis, there is potentially valuable information hidden in complex electronic medical records (EMR) systems. In this thesis, several efficient data mining algorithms were explored to discover hidden knowledge in insurance claims data. The first aim was to cluster three levels of information overload(IO) groups among chronic rheumatic disease (CRD) patient groups based on their clinical events extracted from insurance claims data. The second aim was to discover hidden patterns using three renowned pattern mining algorithms: Apriori, frequent pattern growth(FP-Growth), and sequential pattern discovery using equivalence classes(SPADE). The SPADE algorithm was found to be the …

Multimodal Noncontact Diffuse Optical Reflectance Imaging Of Blood Flow And Fluorescence Contrasts, Daniel Irwin

Theses and Dissertations--Biomedical Engineering

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle …

Sleep And Thermoregulation: A Study Of The Effect Of Ambient Temperature Manipulation On Mouse Sleep Architecture, Asma'a A. Ajwad

Theses and Dissertations--Biomedical Engineering

Good quality sleep is essential for mental and physical health. Inadequate sleep impacts memory consolidation, learning and cognition, immune function, autonomic regulation, physical performance, and other vital functions. In many neurological disorders that are associated with sleep problems such as epilepsy and Alzheimer’s disease, changes in brain circuitry affect sleep-wake regulation mechanisms; this is reflected in anomalous sleep-wake architecture and usually accompanied by poor sleep depth. Thus, over many years, many approaches have been tried in humans and animal models with the goal of improving sleep quality. Unfortunately, each of those approaches comes with limitations or side effects. Thus, there …

Design And Analysis Of A 3d-Printed, Thermoplastic Elastomer (Tpe) Spring Element For Use In Corrective Hand Orthotics, Kevin Thomas Richardson

Theses and Dissertations--Mechanical Engineering

This thesis proposes an algorithm that determine the geometry of 3D-printed, custom-designed spring element bands made of thermoplastic elastomer (TPE) for use in a wearable orthotic device to aid in the physical therapy of a human hand exhibiting spasticity after stroke. Each finger of the hand is modeled as a mechanical system consisting of a triple-rod pendulum with nonlinear stiffness at each joint and forces applied at the attachment point of each flexor muscle. The system is assumed quasi-static, which leads to a torque balance between the flexor tendons in the hand, joint stiffness and the design force applied to …

Lower Back Biomechanics At Non-Chronic Stage Of Low Back Pain, Iman Shojaei

Theses and Dissertations--Biomedical Engineering

Prior studies have reported differences in lower back biomechanics during activities of daily living between individuals with and without chronic low back pain (LBP). Nevertheless, the literature on lower back biomechanics of patients with non-chronic LBP is scant. Therefore, the objective of this study, as the first step towards future prospective studies, was to investigate the lower back biomechanics in patients with non-chronic LBP. Case-control studies were conducted wherein measures of lumbo-pelvic coordination during bending and return tasks as well as measures of mechanical demand on the lower back during lifting tasks in the sagittal plane were investigated between patients …

Synthesis And Characterization Of Blue Light Poly(Β-Amino Ester)S, Nicholas John Kohrs

Theses and Dissertations--Biomedical Engineering

Volumetric muscle loss (VML) is a debilitating injury which results in full or partial loss of function. Current clinical options utilize tissue grafts and bracing to restore function. Tissue graft implantation oftentimes leads to serious complications, some of which end in graft rejection and thereby necessitate further surgeries and procedures. Polymeric scaffolds show promise as scaffolding systems due to their mechanical properties and overall degradation profiles. Scaffolds need appropriate mechanical properties, 10-60 kPa modulus, and overall degradation times, five days to two weeks, to initiate tissue regeneration. Poly(β-amino ester)s (PBAE), a class of synthetic polymers, act as a safe biocompatible …

Characterization And Engineering Of Human Proteins As Therapeutic Candidates, Kyungbo Kim

Theses and Dissertations--Pharmacy

Protein engineering has been a useful tool in the fight against human diseases. Human insulin was the first recombinant DNA-derived therapeutic protein (Humulin^®) approved by the US FDA in 1982. However, many of the early protein drugs were only recombinant versions of natural proteins with no modification of their primary amino acid sequence and most of them did not make optimal drug products mainly due to their short half-life or suboptimal affinity, leading to poor therapeutic efficacy. The difficulty in the large-scale production of some therapeutic proteins was another important issue. In the past three decades, different protein …

Surface Functionalization Via Photoinitiated Radical Polymerization For Rare Cell Isolation And Mechanical Protection, Calvin Frank Cahall

Theses and Dissertations--Chemical and Materials Engineering

Surface functionalization of living cells for cell therapeutics has gained substantial momentum in the last two decades. From encapsulating islets of Langerhans, to cell laden gels for tissue scaffolds, to individual cell encapsulation in thin hydrogels, to surface adhesives and inert surface camouflage, modification of living cell surfaces has a wide array of important applications. Here we use hydrogel encapsulation of individual cells as a mode of protection from mechanical forces for high throughput cell printing, and chemical stimuli for the isolation of rare cells in blood.

In the first study, we review methods of surface functionalization and establish a …