Doctor of Philosophy

dissertationMilitary personnel with amputations face unique challenges due to their short residual limbs and high incidences of multiple limb loss sustained after blast injuries. However, transcutaneous osseointegrated implant (TOI) technology may provide an alternative for individuals with poor socket tolerance by allowing a structural and functional connection between living bone and the surface of a load bearing implant. While TOI has improved activity levels in European patients with limb loss, a lengthy rehabilitation period has limited the expansion of this technology, and may be accelerated with electrical stimulation. The unique advantage of electrically induced TOI is that the exposed exoprosthetic attachment may function as a cathode for regulating electrical current while also serving as the means of prosthetic limb attachment to the host bone. Using this design principle, the goal of this dissertation was to investigate the potential of electrical stimulation for enhancing the rate and magnitude of skeletal fixation at the periprosthetic interface using the implant as a cathode. Although previous studies have examined electrical stimulation for healing atrophic nonunions, inconsistent results have required new predictive measures. Therefore, finite element analysis (FEA) was used as a prerequisite for estimating electric field and current density magnitudes prior to in vivo experimentation. Retrospective computed tomography scans from 11 service members (28.3 ± 5.0 years) demonstrated the feasibility of electrically induced TOI, but variability in residual limb anatomy and the presence of heterotopic ossification confirmed the necessity for patient-specific modeling. Electrically induced osseointegration was also evaluated in vivo in skeletally mature rabbits after establishing design principles based on in vitro cell culturing and FEA. Data from the animal experiment indicated that there were no statistical differences for the appositional bone index (ABI), mineral apposition rate and porosity between the electrically stimulated implants and the unstimulated control implants (UCI). Higher mechanical push-out forces were observed for the UCI group at 6 weeks (p=0.034). In some cases, qualitative backscattered electron images and ABI did indicate that direct current may hold promise for improving suboptimal implant "fit and fill," as bone ongrowth around the cathode was observed despite not having direct contact with the endosteum

Transient bioimpedance monitoring of mechanotransduction in artificial tissue during indentation

Mechanotransduction is of fundamental importance in cell physiology, facilitating sensing in touch and hearing as well as tissue development and wound healing. This study used an impedance sensor to monitor the effective resistance and permittivity of artificial tissues, alginate hydrogel with encapsulated fibroblasts, which were kept viable through the use of a bespoke microfluidic system. The observed transient impedance responses upon the application of identical compressive normal loads differed between acellular hydrogels and hydrogels in which fibroblasts were encapsulated. These differences resulted from changes in the conductivity and permeability of the hydrogel due to the presence of the encapsulated fibroblasts, and transient changes in ion concentrations due to mechanotransduction effects

Tissue Ischemia Monitoring Using Impedance Spectroscopy: Clinical Evaluation

Ischemia is a condition of decreased tissue viability caused by a lack of perfusion, which prevents the delivery of oxygen and nutrients to biological tissue. Ischemia plays a major role in many clinical disorders, yet there are limited means by which tissue viability can be assessed. The long-term objective of this research is to develop a non-invasive or non-contact instrument for quantifying human tissue ischemia. Skeletal muscle ischemia is evaluated at this stage because skeletal muscle is easily accessible, its ischemia represents a clinical problem, and it can endure short periods of ischemia without suffering permanent injury. The ischemia monitor designed for this study is based on impedance spectroscopy, the measurement of tissue impedance at various frequencies. This study had three major goals. The first goal was to improve upon the design of the ischemia monitor to achieve optimal system performance in a clinical environment. Major considerations included electrode sterility, instrument mobility, and electrosurgical unit interference. The second goal was to collect both impedance and pH data from human subjects undergoing tourniquet surgeries, which induce skeletal muscle ischemia and result in changes of the tissue\u27s pH and impedance. The average in recorded pH during ischemia was 0.0053 pH units/minute and the average change in Ro was -0.1481 Ohms/minute. The third goal was to develop a relationship between parameters of tissue impedance and pH utilizing neural networks. This goal was accomplished in three stages. First, the optimal neural network type for classifying impedance data and pH values was determined. Based on these results, the backpropagation neural network was utilized for all subsequent work. Then, the input parameters of the neural network were optimized using previously collected data. The number of inputs to the previously developed neural network were reduced by 35% (13/20) with a maximum of a 3% reduction in neural network performance. Finally, the neural network was trained and tested using human impedance and pH data. The network was able to correctly estimate tissue pH values with an average error of 0.0440 pH units. Through the course of this research the ischemia monitor based on impedance spectroscopy was improved, a methodology for the use of the instrument in the operating room was developed, and a preliminary relationship between parameters of impedance spectra and pH was established. The results of this research indicate the feasibility of the instrument to monitor both pH and impedance in a clinical setting. Additionally, it was demonstrated that impedance data collected non-invasively could be used to estimate the pH and level of ischemia in human skeletal muscle

Restoring Upper Extremity Mobility through Functional Neuromuscular Stimulation using Macro Sieve Electrodes

The last decade has seen the advent of brain computer interfaces able to extract precise motor intentions from cortical activity of human subjects. It is possible to convert captured motor intentions into movement through coordinated, artificially induced, neuromuscular stimulation using peripheral nerve interfaces. Our lab has developed and tested a new type of peripheral nerve electrode called the Macro-Sieve electrode which exhibits excellent chronic stability and recruitment selectivity. Work presented in this thesis uses computational modeling to study the interaction between Macro-Sieve electrodes and regenerated peripheral nerves. It provides a detailed understanding of how regenerated fibers, both on an individual level and on a population level respond differently to functional electrical stimulation compared to non-disrupted axons. Despite significant efforts devoted to developing novel regenerative peripheral interfaces, the degree of spatial clustering between functionally related fibers in regenerated nerves is poorly understood. In this thesis, bioelectrical modeling is also used to predict the degree of topographical organization in regenerated nerve trunks. In addition, theoretical limits of the recruitment selectivity of the device is explored and a set of optimal stimulation paradigms used to selectively activate fibers in different regions of the nerve are determined. Finally, the bioelectrical model of the interface/nerve is integrated with a biomechanical model of the macaque upper limb to study the feasibility of using macro-sieve electrodes to achieve upper limb mobilization

Impedance Analysis of Tissues in nsPEF Treatment for Cancer Therapy

Nanosecond pulsed electric field (nsPEF) for cancer therapy is characterized by applications of high voltage pulses with low pulsed energy to induce non-thermal effects on tissues such as tumor ablation. It nonthermally treats tissues via electroporation. Electroporation is the increase in permeabilization of a cell membrane due to the application of high pulsed electric field. The objective of this study was to investigate the effect of nsPEF on tissue by monitoring the tissue’s impedance in real-time. Potato slices (both untreated and electroporated), and tumors extracted from female BALBc mice were studied. 100ns, 1-10kV pulses were applied to the tissues using a four-pin electrode at a pulse repetition frequency of 3Hz. The impedance change during the treatment was recorded by a custom made V-I monitor, and a network analyzer measured the impedance before and after treatment over a frequency range of 100kHz to 30MHz. In addition, system calibration was conducted to ensure the accuracy of the measurements. This includes determination of the attenuation offered by the V-I monitor measured to be 60dB and the cell constant K which represents the geometry of the four-pin electrode measured to be 0.8453����−1 (±0.02cm). Results show that the impedance of tissue reduced with increasing number of pulses and voltage applied, up to 44.4% and 22.3% decrease in the impedance of potato and tumor tissues were respectively observed. Also, the impedance values were higher at lower frequencies compared to those at higher frequencies. This is due to the high resistance of the membrane at low frequencies

Multiscale Modeling of the Ventricles: From Cellular Electrophysiology to Body Surface Electrocardiograms

This work is focused on different aspects within the loop of multiscale modeling: On the cellular level, effects of adrenergic regulation and the Long-QT syndrome have been investigated. On the organ level, a model for the excitation conduction system was developed and the role of electrophysiological heterogeneities was analyzed. On the torso level a dynamic model of a deforming heart was created and the effects of tissue conductivities on the solution of the forward problem were evaluated

Alterations in Localized Electrical Impedance Myography of Biceps Brachii Muscles Paralyzed by Spinal Cord Injury

This study assessed electrical impedance myography (EIM) changes after spinal cord injury (SCI) with a localized multifrequency technology. The EIM measurement was performed on the biceps brachii muscle at rest condition of 17 cervical SCI subjects, and 23 neurologically intact subjects as control group. The results showed that there was a significant decrease in muscle reactance (X) and phase angle (θ) at selected frequencies (i.e., 50 and 100 kHz) in SCI compared to control. There was no significant difference in muscle resistance (R) between the two groups. The anisotropy examination revealed that SCI group had a decreased anisotropy ratio in resistance. In addition, the multifrequency spectrum analysis showed a decreased slope of the log(freq)-resistance regression in SCI group when compared to healthy control. Findings of the EIM changes are related to inherit muscle changes after the injury. Since EIM requires no patient effort and is quick and convenient to conduct, it may provide a useful tool for examination of paralyzed muscle changes after SCI

National Aeronautics and Space Administration (NASA)/American Society for Engineering Education (ASEE) Summer Faculty Fellowship Program, 1989, volume 1

The 1989 Johnson Space Center (JSC) National Aeronautics and Space Administration (NASA)/American Society for Engineering Education (ASEE) Summer Faculty Fellowship Program was conducted by Texas A and M University and JSC. The 10-week program was operated under the auspices of the ASEE. The program at JSC, as well as the programs at other NASA Centers, was funded by the Office of University Affairs, NASA Headquarters, Washington, D.C. The objectives of the program, which began nationally in 1964 and at JSC in 1965, are: (1) to further the professional knowledge of qualified engineering and science faculty members; (2) to stimulate an exchange of ideas between participants and NASA; (3) to enrich and refresh the research and teaching activities of participants' institutions; and (4) to contribute to the research objective of the NASA Centers