Biomedical Engineering and Bioengineering Commons^™

Ex Vivo Electrochemical Measurement Of Glutamate Release During Spinal Cord Injury, James K. Nolan, Tran N. H. Nguyen, Mara Fattah, Jessica C. Page, Riyi Shi, Hyowon Lee

Weldon School of Biomedical Engineering Faculty Publications

Excessive glutamate release following traumatic spinal cord injury (SCI) has been associated with exacerbating the extent of SCI. However, the mechanism behind sustained high levels of extracellular glutamate is unclear. Spinal cord segments mounted in a sucrose double gap recording chamber are an established model for traumatic spinal cord injury. We have developed a method to record, with micro-scale printed glutamate biosensors, glutamate release from ex vivo rat spinal cord segments following injury. This protocol would work equally well for similar glutamate biosensors.

An Automated Workflow For Quantifying Rna Transcripts In Individual Cells In Large Data-Sets, Matthew C. Pharris, Tzu-Ching Wu, Xinping Chen, Xu Wang, David M. Umulis, Vikki M. Weake, Tamara L. Kinzer-Ursem

Weldon School of Biomedical Engineering Faculty Publications

Advanced molecular probing techniques such as single molecule fluorescence in situ hybridization (smFISH) or RNAscope can be used to assess the quantity and spatial location of mRNA transcripts within cells. Quantifying mRNA expression in large image sets usually involves automated counting of fluorescent spots. Though conventional spot counting algorithms may suffice, they often lack high-throughput capacity and accuracy in cases of crowded signal or excessive noise. Automatic identification of cells and processing of many images is still a challenge. We have developed a method to perform automatic cell boundary identification while providing quantitative data about mRNA transcript levels across many …

A Potential New Technique To Estimate The Origins Of Focal Atrial Tachycardias From 12-Lead Electrocardiograms, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Background: This brief report presents a potential new technique for locating the sites of origin of focal atrial tachycardias from standard 12-lead electrocardiograms. Methods: Estimated P wave vector coordinates are derived from leads I, aVF, V1 and V2, and mapped to a three dimensional coordinate system in space. A simple graphical method is used to find the back projection of the P wave vector onto the surface of atrial muscle to estimate the most likely site of origin of the tachycardia. Results: Graphical back projection correctly identified foci of atrial tachycardias in 19 of 19 cases described in the most …

Optimizing Strategies For Population-Based Chlamydia Infection Screening Among Young Women: An Age-Structured System Dynamics Approach Infectious Disease Epidemiology, Yu Teng, Nan Kong, Wanzhu Tu

Weldon School of Biomedical Engineering Faculty Publications

Background

Chlamydia infection (CT) is one of the most commonly reported sexually transmitted diseases. It is often referred to as a “silent” disease with the majority of infected people having no symptoms. Without early detection, it can progress to serious reproductive and other health problems. Economical identification of asymptomatically infected is a key public health challenge. Increasing evidence suggests that CT infection risk varies over the range of adolescence. Hence, age-dependent screening strategies with more frequent testing for certain age groups of higher risk may be cost-saving in controlling the disease.

Methods

We study the optimization of age-dependent screening strategies …

The Origin Of Korotkoff Sounds And The Accuracy Of Auscultatory Blood Pressure Measurements, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

This study explores the hypothesis that the sharper, high frequency Korotkoff sounds come from resonant motion of the arterial wall, which begins after the artery transitions from a buckled state to an expanding state. The motion of one mass, two nonlinear springs, and one damper, driven by transmural pressure under the cuff, are used to model and compute the Korotkoff sounds according to principles of classical Newtonian physics. The natural resonance of this spring-mass-damper system provides a concise, yet rigorous, explanation for the origin of Korotkoff sounds. Fundamentally, wall stretching in expansion requires more force than wall bending in buckling. …

Noninvasive Measurement Of Cardiac Stroke Volume Using Pulse Wave Velocity And Aortic Dimensions: A Simulation Study, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Background: Concerns about the cost-effectiveness of invasive hemodynamic monitoring in critically ill patients using pulmonary artery catheters motivate a renewed search for effective noninvasive methods to measure stroke volume. This paper explores a new approach based on noninvasively measured pulse wave velocity, pulse contour, and ultrasonically determined aortic cross sectional area. Methods: The Bramwell-Hill equation relating pulse wave velocity to aortic compliance is applied. At the time point on the noninvasively measured pulse contour, denoted th, when pulse amplitude has fallen midway between systolic and diastolic values, the portion of stroke volume remaining in the aorta, and in turn the …

A Compact Theory Of Magnetic Nerve Stimulation: Predicting How To Aim, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Background: A compact theory that predicts quantitatively when and where magnetic neurostimulation will occur is needed as a guide to therapy, ideally providing a single equation that defines the target volume of tissue excited by single or dual coils. Methods: A first-principles analysis of magnetic stimulation incorporating a simplified description of electromagnetic fields and a simplified cable theory of the axon yields a mathematical synthesis predicting how to aim. Results: Nerve stimulation produced by a single circular coil having one or more closely packed turns occurs in donut shaped volume of tissue beneath the coil. Axons spanning several millimeters are …

Choosing Inclusion Criteria That Minimize The Time And Cost Of Clinical Trials, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

AIM: To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria. METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure …

We Still Need A Real-Time Hemodynamic Monitor For Cpr, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

No abstract provided.

The Case For Interposed Abdominal Compression Cpr In Hospital Settings, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Interposed abdominal compression (IAC)-CPR includes all steps of standard external CPR with the addition of manual mid-abdominal compressions in counterpoint to the rhythm of chest compressions. IAC-CPR can increase blood flow during CPR about two fold compared to standard CPR without IAC, as shown by multiple studies in computer and animal models. The technique increases the rate return of spontaneous circulation (ROSC) for in-hospital resuscitations from roughly 25% to 50%. Improved survival to discharge is demonstrated in two in-hospital trials. IAC as an adjunct technique is quickly taught and is less complex than most other basic life support maneuvers. A …

Differential Mitochondrial Toxicity Screening And Multi- Parametric Data Analysis, Maria V. Tsiper, Jennifer Sturgis, Larisa V. Avramova, Shilpa Parakh, Raymond Fatig, Ana Juan-García, Nianyu Li, Bartek Rajwa, Padma Narayanan, C. W. Wualls Jr., Joseph P. Robinson, Vincent J. Davisson

Weldon School of Biomedical Engineering Faculty Publications

Early evaluation of new drug entities for their potential to cause mitochondrial dysfunction is becoming an important task for drug development. Multi-parametric high-content screening (mp-HCS) of mitochondrial toxicity holds promise as a lead in-vitro strategy for drug testing and safety evaluations. In this study, we have developed a mp-HCS and multi-parametric data analysis scheme for assessing cell responses to induced mitochondrial perturbation. The mp-HCS measurements are shown to be robust enough to allow for quantitative comparison of biological systems with different metabolic pathways simulated by alteration of growth media. Substitution of medium glucose for galactose sensitized cells to drug action …

Predicting Success Or Failure Of Immunotherapy For Cancer: Insights From A Clinically Applicable Mathematical Model, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

The objective of this study was to create a clinically applicable mathematical model of immunotherapy for cancer and use it to explore differences between successful and unsuccessful treatment scenarios. The simplified predator-prey model includes four lumped parameters: tumor growth rate, g; immune cell killing efficiency, k; immune cell signaling factor, λ; and immune cell half-life decay, μ. The predator-prey equations as functions of time, t, for normalized tumor cell numbers, y, (the prey) and immunocyte numbers, x, (the predators) are: dy/dt = gy – kx and dx/dt = λxy – μx. A parameter estimation procedure that capitalizes on available clinical …

Optimizing Electrode Placement For Hemodynamic Benefit In Cardiac Resynchronization Therapy, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Background: Research is needed to explore the relative benefits of alternative electrode placements in biventricular and left ventricular pacing for heart failure with left bundle branch block (LBBB). Methods: A fast computational model of the left ventricle, running on an ordinary laptop computer, was created to simulate the spread of electrical activation over the myocardial surface, together with the resulting electrocardiogram, segmental wall motion, stroke volume, and ejection fraction in the presence of varying degrees of mitral regurgitation. Arbitrary zones of scar and blocked electrical conduction could be modeled. Results: Simulations showed there are both sweet spots and poor spots …

Quantitative Reappraisal Of The Helmholtz-Guyton Resonance Theory Of Frequency Tuning In The Cochlea, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

To explore the fundamental biomechanics of sound frequency transduction in the cochlea, a two-dimensional analytical model of the basilar membrane was constructed from first principles. Quantitative analysis showed that axial forces along the membrane are negligible, condensing the problem to a set of ordered one-dimensional models in the radial dimension, for which all parameters can be specified from experimental data. Solutions of the radial models for asymmetrical boundary conditions produce realistic deformation patterns. The resulting second-order differential equations, based on the original concepts of Helmholtz and Guyton, and including viscoelastic restoring forces, predict a frequency map and amplitudes of deflections …

Anterior-Posterior Impedance Cardiography: A New Approach To Accurate, Non-Invasive Monitoring Of Cardiac Function, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

The conventional impedance cardiogram is a record of pulsatile changes in the electrical impedance of the chest with each heartbeat. The signal seems intuitively related to cardiac stroke volume. However doubts persist about the validity of stroke volume measurements based on electrical impedance. This paper presents a new electrical axis for impedance cardiography that is perpendicular to the conventional head-to-foot axis in an anterior-posterior direction. Dual chest and back electrodes are concentric, permitting tetrapolar technique. A relatively simple analytical model is developed, and this model is validated in a three-dimensional finite element model of current flow through the human chest. …

Methods For Calculating Coronary Perfusion Pressure During Cpr, Michael P. Otlewski, Leslie A. Geddes, Michael Pargett, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Coronary perfusion pressure (CPP) is a major indicator of the effectiveness of cardiopulmonary resuscitation in human and animal research studies; however methods for calculating CPP differ among research groups. Here we compare the 6 published methods for calculating CPP using the same data set of aortic (Ao) and right atrial (RA) blood pressures. CPP was computed using each of the 6 calculation methods in an anesthetized pig model, instrumented with catheters with Cobe pressure transducers. Aortic and right atrial pressures were recorded continuously during electrically induced ventricular fibrillation and standard CPR. CPP calculated from the same raw data set by …

Neonatal Cpr: Room At The Top—A Mathematical Study Of Optimal Chest Compression Frequency Versus Body Size, Charles F. Babbs, Andrew Meyer, Vinay Nadkarni

Weldon School of Biomedical Engineering Faculty Publications

Objective: To explore in detail the expected magnitude of systemic perfusion pressure during standard CPR as a function of compression frequency for different sized people from neonate to adult. Method: A 7-compartment mathematical model of the human cardiopulmonary system—upgraded to include inertance of blood columns in the aorta and vena cavae—was exercised with parameters scaled to reflect changes in body weight from 1 to 70 kg. Results: Maximal systemic perfusion pressure occurs at chest compression rates near 60, 120, 180, and 250 per minute for subjects weighing 70, 10, 3, and 1 kg, respectively. Such maxima are predicted by analytical …

Quantitative Prediction Of Body Surface Potentials From Myocardial Action Potentials Using A Summed Dipole Model, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

This paper demonstrates quantitatively, using streamlined mathematics, how the transmembrane ionic currents in individual cardiac muscle cells act to produce the body surface potentials of the electrocardiogram (ECG). From fundamental principles of electrostatics, anatomy, and physiology, one can characterize the strength of apparent dipoles along a wavefront of depolarization in a local volume of myocardium. Net transmembrane flow of ionic current in actively depolarizing or repolarizing tissue induces extracellular current flow, which sets up a field of electrical potential that resembles that of a dipole. The local dipole strength depends upon the tissue cross section, the tissue resistivity, the resting …

A New Paradigm For Human Resuscitation Research Using Intelligent Devices, Charles F. Babbs, Andre E. Kemeny, Weilun Quan, Gary Freeman

Weldon School of Biomedical Engineering Faculty Publications

Objectives: To develop new methods for studying correlations between the performance and outcome of resuscitation efforts in real-world clinical settings using data recorded by automatic devices such as automatic external defibrillators (AEDs), and to explore effects of shock timing and chest compression depth in the field. Methods: In 695 records of AED use in the pre-hospital setting, continuous compression data were recorded using AEDs capable of measuring sternal motion during compressions, together with timing of delivered shocks and the electrocardiogram. In patients who received at least one shock, putative return of spontaneous circulation (P-ROSC) was defined as a regular, narrow …

Statistical Analysis Of Joint Short-Term And Long-Term Survival In Resuscitation Research, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Objective: To develop statistical tools that utilize combined initial survival data and post-resuscitation survival data to test the null hypothesis that true, population-wide outcomes following experimental CPR interventions are not different from control. Method: A new test statistic, d2, for evaluating Type 1 error is derived from a bivariate, two-dimensional analysis of categorical initial resuscitation and post-resuscitation survival data, which are statistically independent because they are obtained during non-overlapping periods of time. The d2 test statistic, which is distributed as a chi-squared distribution, is derived from first principles and validated using Monte Carlo methods of computer simulation for thousands of …

A Novel Open Field Activity Detector To Determine Spatial And Temporal Movement Of Laboratory Animals After Injury And Disease, Andrew O. Koob, John Cirillo, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Among the wide range of tests for laboratory animal behavior after neurological injury or disease, each has its benefits and drawbacks. The varied behavior that an animal exhibits makes it difficult to decide which test to use. However, a fundamental instinct for the laboratory animal is to explore when placed in a new environment. A way to test exploratory behavior is in the open field. Here, we introduce a simple activity box without the use of video equipment to determine the exploratory movement of a rat after traumatic brain injury. The activity box is an open field, and the rat …

Design Of Near-Optimal Waveforms For Chest And Abdominal Compression And Decompression In Cpr Using Computer-Simulated Evolution, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Objective: To discover design principles underlying the optimal waveforms for external chest and abdominal compression and decompression during cardiac arrest and CPR. Method: A 14-compartment mathematical model of the human cardiopulmonary system is used to test successive generations of randomly mutated external compression waveforms during cardiac arrest and resuscitation. Mutated waveforms that produced superior mean perfusion pressure became parents for the next generation. Selection was based upon either systemic perfusion pressure (SPP=thoracic aortic minus right atrial pressure) or upon coronary perfusion pressure (CPP=thoracic aortic pressure minus myocardial wall pressure). After simulations of 64,414 individual CPR episodes, 40 highly evolved waveforms …

A New Biomechanical Head Injury Criterion, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

This paper presents a new analysis of the physics of closed head injury caused by intense acceleration of the head. At rest a 1 cm gap filled with cerebrospinal fluid (CSF) separates the human brain from the skull. During impact whole head acceleration induces artificial gravity within the skull. Because its density differs slightly from that of CSF, the brain accelerates, strikes the inner aspect of the rigid skull, and undergoes viscoelastic deformation. Analytical methods for a lumped parameter model of the brain predict internal brain motions that correlate well with published high-speed photographic studies. The same methods predict a …

Optimal Control Theory Applied To A Difference Equation Model Of Cardiopulmonary Resuscitation, Eunok Jung, Charles F. Babbs, Suzanne Lenhart, Vladimir A. Protopoescu

Weldon School of Biomedical Engineering Faculty Publications

Objective: To apply the mathematical techniques of optimal control theory (OCT) to a validated model of the human circulation during cardiopulmonary resuscitation (CPR), so as to discover improved waveforms for chest compression and decompression that maximize the systemic perfusion pressure (SPP). Methods: The human circulatory system is represented by seven difference equations, which describe the pressure changes in systemic vascular compartments caused by chest compression. The forcing term is the intrathoracic pressure generated by the external chest compression, which is taken as the “control” variable for the system. The optimum waveform of this forcing pressure as a function of time, …

A Dose-Response Curve For The Negative Bias Pressure Of An Intrathoracic Pressure Regulator During Cpr, Charles F. Babbs, Demetris Yannopoulos

Weldon School of Biomedical Engineering Faculty Publications

An intrathoracic pressure regulator (ITPR) is a device that can be added to the external end of an endotracheal tube to create controlled negative airway pressure between positive pressure ventilations. The resulting downward bias of the airway pressure baseline promotes increased venous return and enhanced circulation during CPR and also during hypovolemic shock. In the present study we exercised a mathematical model of the human cardiopulmonary system, including airways, lungs, a 4 chambered heart, great vessels, peripheral vascular beds, and the biomechanics of chest compression and recoil, to determine the relationship between systemic perfusion pressure during CPR and the value …

Intravenous Polyethylene Glycol Inhibits The Loss Of Cerebral Cells After Brain Injury, Andrew O. Koob, Bradley S. Duerstock, Charles F. Babbs, Yinlong Sun, Richard B. Borgens

Weldon School of Biomedical Engineering Faculty Publications

We have tested the effectiveness of polyethylene glycol (PEG) to restore the integrity of neuronal membranes after mechanical damage secondary to severe traumatic brain injury (TBI) produced by a standardized head injury model in rats. We provide additional detail on the standardization of this model, particularly the use and storage of foam bedding that serves to both support the animal during the impact procedure and to dampen the acceleration of the brass weight. Further, we employed a dye exclusion technique using ethidium bromide (EB; quantitative evaluation) and horseradish peroxidase (HRP; qualitative evaluation). Both have been successfully used previously to evaluate …

Biophysics Of Cardiopulmonary Resuscitation With Periodic Z-Axis Acceleration Of Abdominal Compression At Aortic Resonant Frequencies, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Periodic z-axis acceleration (pGz)-CPR involves oscillating motion of a whole patient in the head-to-foot dimension on a mechanized table. The method is able to sustain blood flow and long-term survival during and after prolonged cardiac arrest in anesthetized pigs. However, the exact mechanism by which circulation of blood is created has remained unknown. Objectives: To explain the hemodynamic mechanism of pGz-CPR and to suggest theoretically useful improvements. Method: Computer modeling using a hybrid analytical-numerical approach, based upon Newton’s second law of motion for fluid columns in the aorta and vena cavae, Ohm’s law for resistive flow through vascular beds, and …

Effects Of An Impedance Threshold Valve Upon Hemodynamics In Standard Cpr: Studies In A Refined Computational Model, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

An impedance threshold valve (ITV) is a new airway adjunct for resuscitation that permits generation of a small vacuum in the chest during the recoil phase of chest compression. Objectives: To explore in detail the expected magnitude and the hemodynamic mechanisms of circulatory augmentation by an ITV in standard CPR. Method: A 14-compartment mathematical model of the human cardiopulmonary system—upgraded to include applied chest compression force, elastic recoil of the chest wall, anatomic details of the heart and lungs, and the biomechanics of mediastinal compression—is exercised to explore the conditions required for circulatory augmentation by an ITV during various modes …

Relative Effectiveness Of Interposed Abdominal Compression Cpr: Sensitivity Analysis And Recommended Compression Rates, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

Interposed abdominal compression (IAC)-CPR incorporates alternating chest and abdominal compressions to generate enhanced artificial circulation during cardiac arrest. The technique has been generally successful in improving blood flow and survival compared to standard CPR; however some questions remain. Objective: To determine "why does IAC-CPR produce more apparent benefit in some subjects than in others? and "what is the proper compression rate, given that there are actually two compressions (chest and abdomen) in each cycle?" Method: Computer models provide a means to search for subtle effects in complex systems. The present study employs a validated 12-compartment mathematical model of the human …

Brain Motion And Deformation During Closed Head Injury In The Presence Of Cerebrospinal Fluid, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Publications

This paper presents a new analysis of the physics of closed head injury following brief, intense acceleration of the head. It focuses upon the buoyancy of the brain in cerebrospinal fluid, which protects against damage, the propagation of strain waves through the brain substance, which causes damage, and the concentration of strain in critical anatomic regions, which magnifies damage. Numerical methods are used to create animations or "movies" of brain motion and deformation. Initially a 1 cm gap filled with cerebrospinal fluid (CSF) separates the brain from the skull. Whole head acceleration induces artificial gravity within the skull. The brain …