Pressure injuries (pressure ulcers, bed sores) are a localized injury to skin and/or underlying tissues as a result of excessive pressure with or without shear force or friction. These injuries are painful, increase risk of secondary infection, have prolonged healing times (months), and cost the U.S. healthcare system 26.8 billion dollars annually. While these injuries are considered preventable, pressure injuries have an overall prevalence of 12.3% in U.S. healthcare facilities with 40% of all pressure injury incidents being facility acquired. The current clinical standard of rotating patients every two hours to offload tissues and performing visual skin assessments is not sufficient for preventing all pressure injuries. The susceptibility to pressure injury formation varies between individuals, and visual skin assessments cannot detect tissue damage below the skin surface. Objective and non-invasive methods for detecting early signs of tissue damage, such as ultrasound and subepidermal moisture scanners, have shown promise in detecting subcutaneous damage. However, these spot scan techniques require trained personnel for interpretation and can lag the pressure loading event by more than 2 days. As part of an ongoing effort to develop an objective and wearable noninvasive monitor to detect early changes related to pressure injury formation, a low-cost, battery-powered bioimpedance sensor was developed and tested on ex vivo and in vivo animal models. The developed sensor is capable of measuring typical human skin impedances with errors of less than 6% as determined using a human skin equivalent electrical model. Continuous bioimpedance-based monitors need to be capable of measuring accurately during changing skin conditions, such as changes in temperature and sweating. The effect of changes in skin microclimate on bioimpedance measurements was investigated using an ex vivo porcine dermis model. We found that increased tissue hydration, simulated by washing porcine dermis in saline, can significantly impact impedance magnitude and phase angle measurements. Finally, an in vivo pressure ulcer rat model was used to determine the relationship between bioimpedance measures, tissue loading intensities, and clinical ulcer staging. Changes between bioimpedance measures before and immediately following the pressure loading event had moderate (0.55) to strong (0.8) linear and rank order correlation with tissue loading intensity (pressure x time). Thresholds were determined to separate clinical ulcer stages via bioimpedance measures taken 3 days prior to visual skin assessment and found that the majority of ulcers could be properly categorized into ulcer/no ulcer groups. These results indicate that bioimpedance is a promising parameter in the development of a continuous noninvasive system for early pressure ulcer detection.

Pressure injuries (pressure ulcers, bed sores) are a localized injury to skin and/or underlying tissues as a result of excessive pressure with or without shear force or friction. These injuries are painful, increase risk of secondary infection, have prolonged healing times (months), and cost the U.S. healthcare system 26.8 billion dollars annually. While these injuries are considered preventable, pressure injuries have an overall prevalence of 12.3% in U.S. healthcare facilities with 40% of all pressure injury incidents being facility acquired. The current clinical standard of rotating patients every two hours to offload tissues and performing visual skin assessments is not sufficient for preventing all pressure injuries. The susceptibility to pressure injury formation varies between individuals, and visual skin assessments cannot detect tissue damage below the skin surface. Objective and non-invasive methods for detecting early signs of tissue damage, such as ultrasound and subepidermal moisture scanners, have shown promise in detecting subcutaneous damage. However, these spot scan techniques require trained personnel for interpretation and can lag the pressure loading event by more than 2 days. As part of an ongoing effort to develop an objective and wearable noninvasive monitor to detect early changes related to pressure injury formation, a low-cost, battery-powered bioimpedance sensor was developed and tested on ex vivo and in vivo animal models. The developed sensor is capable of measuring typical human skin impedances with errors of less than 6% as determined using a human skin equivalent electrical model. Continuous bioimpedance-based monitors need to be capable of measuring accurately during changing skin conditions, such as changes in temperature and sweating. The effect of changes in skin microclimate on bioimpedance measurements was investigated using an ex vivo porcine dermis model. We found that increased tissue hydration, simulated by washing porcine dermis in saline, can significantly impact impedance magnitude and phase angle measurements. Finally, an in vivo pressure ulcer rat model was used to determine the relationship between bioimpedance measures, tissue loading intensities, and clinical ulcer staging. Changes between bioimpedance measures before and immediately following the pressure loading event had moderate (0.55) to strong (0.8) linear and rank order correlation with tissue loading intensity (pressure x time). Thresholds were determined to separate clinical ulcer stages via bioimpedance measures taken 3 days prior to visual skin assessment and found that the majority of ulcers could be properly categorized into ulcer/no ulcer groups. These results indicate that bioimpedance is a promising parameter in the development of a continuous noninvasive system for early pressure ulcer detection.

Electrical bioimpedance spectroscopy (EBIS) has been used to assess the status or composition of various types of tissue, and examples of EBIS include body composition analysis (BCA) and tissue characterisation for skin cancer detection. EBIS is a non-invasive method that has the potential to provide a large amount of information for diagnosis or monitoring purposes, such as the monitoring of pulmonary oedema, i.e., fluid accumulation in the lungs. However, in many cases, systems based on EBIS have not become generally accepted in clinical practice. Possible reasons behind the low acceptance of EBIS could involve inaccurate models; artefacts, such as those from movements; measurement errors; and estimation errors. Previous thoracic EBIS measurements aimed at pulmonary oedema have shown some uncertainties in their results, making it difficult to produce trustworthy monitoring methods. The current research hypothesis was that these uncertainties mostly originate from estimation errors. In particular, time-varying behaviours of the thorax, e.g., respiratory and cardiac activity, can cause estimation errors, which make it tricky to detect the slowly varying behaviour of this system, i.e., pulmonary oedema. The aim of this thesis is to investigate potential sources of estimation error in transthoracic impedance spectroscopy (TIS) for pulmonary oedema detection and to propose methods to prevent or compensate for these errors.   This work is mainly focused on two aspects of impedance spectrum estimation: first, the problems associated with the delay between estimations of spectrum samples in the frequency-sweep technique and second, the influence of undersampling (a result of impedance estimation times) when estimating an EBIS spectrum. The delay between frequency sweeps can produce huge errors when analysing EBIS spectra, but its effect decreases with averaging or low-pass filtering, which is a common and simple method for monitoring the time-invariant behaviour of a system. The results show the importance of the undersampling effect as the main estimation error that can cause uncertainty in TIS measurements.  The best time for dealing with this error is during the design process, when the system can be designed to avoid this error or with the possibility to compensate for the error during analysis. A case study of monitoring pulmonary oedema is used to assess the effect of these two estimation errors. However, the results can be generalised to any case for identifying the slowly varying behaviour of physiological systems that also display higher frequency variations.  Finally, some suggestions for designing an EBIS measurement system and analysis methods to avoid or compensate for these estimation errors are discussed. / <p>QC 20140604</p>

Irreversible electroporation (IRE) is a local ablation technique that has been shown to be both safe and effective in the treatment of solid tumors. The treatment typically consists of inserting needle electrodes directly into the treatment zone and applying high-voltage pulses with widths on the order of hundreds of microseconds. These pulses permeabilize tissue leading to loss of homeostasis among the cells in the treatment zone. Predicting these treatments is challenging as the electric field (EF) induced through the electrode configuration is heterogeneous and is affected by several adjustable parameters. Computational treatment planning models aim to provide a visualization of the treatment zone, and they rely on two critical pieces of information: the electric field distribution (EFD) within the tissue, and the lethal EF threshold for the target tissue type. This work primarily aims to quantify tissue properties necessary for computing the EFD for any electrode configuration, for both traditional IRE as well as next-generation high-frequency IRE treatments. Also included is the determination of pancreatic tumor lethal EF threshold using collagen tissue mimics. Additionally, this work builds on previous reports of an optimal resistance reached during IRE by examining the changes in patients' immune cell populations following treatment, and proposing a method of optimizing these populations by monitoring real-time current achieved during IRE. / Doctor of Philosophy / We are in dire need of new options in cancer therapy, especially in the treatment of tumors that are unresectable, particularly aggressive, or resistant to drugs. Irreversible electroporation (IRE) is a local tumor treatment that has been shown to safely and effectively destroy tumor tissue while leaving behind important structures like blood vessels. As IRE treatments depend on the electric field (EF) generated within the target tissue, it is difficult for clinicians to predict the amount of tissue that will be treated ahead of time. This work aims to collect and examine the information about tumors and the surrounding healthy tissue that is critical to models that can help visualize the treatment and ensure the tumor is exposed to enough lethal energy. Additionally, a new and improved, high-frequency version of IRE (H-FIRE) is explored in terms of its impact on how tissue behaves during the delivery of these types of pulses. In addition to informing models of these therapies, we also explore strategies that clinicians can employ during treatment in order to know when to stop in order to avoid over-treating the area.

Bioimpedance is the term given to the complex impedance value that is characteristic of the resistance that biological cells offer to the flow of electric current. The objective of this study is to analyze the differences in the bioimpedance of highly metastatic MDA-MB-231 and normal MCF 10A breast epithelial cells and use this information to detect a very small number of breast cancer cells present in a background of normal breast cells and other cells that are typically present in a human biopsy sample.To accomplish this, a bioimpedance sensor with flat gold microelectrodes on a silicon substrate was designed and fabricated. Suberoylanilide hydroxamic acid (SAHA), an FDA-approved anti-cancer agent was used to improve the sensitivity of the bioimpedance sensor towards cancer cells by selectively modifying their cytoarchitecture. / Master of Science

It has been observed that the normal process of aging is associated with a decline in muscle strength and mass. It has also been observed that total body potassium and intracellular water (ICW) decrease with age, reflecting a loss of body cell mass (BCM), 60% of which is the skeletal muscle. It is generally accepted that traditional high-intensity strength training (ST) regimens can not only attenuate, but in some cases, reverse some of these aging-related changes. Periodization, a nontraditional approach to strength training, has been demonstrated to stimulate more rapid increases in muscle strength than traditional approaches in young adults; however, it has not been comprehensively evaluated in postmenopausal women. Investigators have consistently reported an increase in muscle strength in older adults undergoing both short- and long-term traditional ST programs. It is fairly well accepted that early increases in muscle strength are attributable to neurologic adaptations. There has been less consistency in the literature regarding the timing and nature of changes in muscle quality and mass with ST. Although several investigators have reported increased muscle protein synthesis rates as early as 2 weeks after ST initiation in older adults, the majority of published reports support the notion that significant NET gains in intracellular protein, and thus, gains in muscle mass/volume/hypertrophy do not occur before 9-10 weeks. Changes in intracellular water, which would be expected to occur with changes in intracellular protein, have not been studied during short-term ST interventions in older adults. Bioimpedance spectroscopy (BIS) has been validated as a field technique to accurately measure ICW (and BCM) changes in HIV infected individuals. The primary aim of the current study was to determine if muscle strength would increase in postmenopausal women undergoing a novel (periodized) ST intervention of 10 weeks duration. A secondary aim was to determine if BIS would detect a change in ICW in the study subjects from baseline to study conclusion. Study participants were eleven, healthy postmenopausal women between the ages of 60 and 74 (mean age: 65 ± 4.4 y) who had not engaged in ST in the six months preceding the study. ICW and muscle strength were assessed at baseline and at study conclusion. The ST program was conducted twice a week for 10 weeks at the Senior Center in Blacksburg, VA. Participants performed seven different exercises incorporating upper body and lower body muscle groups. The women performed one set of 8-12 repetitions at an intensity of 80% of one repetition maximum (1 RM) the first week, progressing to 2 sets of 8-12 repetitions at the same intensity during the second week. The remaining weeks consisted of three sets of 8-12 repetitions, performed at an intensity of 80%, 75%, and 70% of their current 1 RM, respectively. One RM was reassessed every other week. The major result from this study was that muscle strength of all trained muscle groups increased in postmenopausal women undergoing 10 weeks of pyramid ST (P<0.05). In addition, the pyramid ST protocol utilized in this study was well-tolerated and resulted in no injuries in any of the older women in the study, indicating that this approach may be used safely in this population. Mean ICW measured by the field method BIS did not change over the course of the study. This result was consistent with other published data reporting no changes in lean body mass or muscle volume/area by more sophisticated techniques. / Master of Science

The thesis is concerned with the analysis of measuring pulse wave velocity in human body with the aid of whole-body multichannel bioimpedance which was developed at ISI AS CR, v.v.i.. The evaluation of pulse wave velocity can provide us with important information about the state of vessel compliance which is one of the basic parameters informing on their physiological state. The examination of the state of vascular system is a very important part of early diagnostics because its pathological states are the main contributor to the rise of cardiovascular diseases and disease mortality. The thesis is concerned with the theoretical analysis together with the available methods of valuation of the state of vascular system that use measuring of pulse wave velocity. The main part of the thesis deals with the analysis of the whole-body multichannel bioimpedance measurement. The proposed and programmed protocol that summarizes and visualizes all obtained information is a part of this thesis. This is currently used as an output of the experimental measurement by this method. Data file for statistical processing contains the values of the pulse wave velocity of 35 healthy volunteers and subsequently the properties of pulse wave are assessed at various excitations.

Functional garments for physiological sensing purposes have been utilized in several disciplinesi.e. sports, firefighting, military and medical. In most of the cases textile electrodes (Textrodes)embedded in the garment are employed to monitor vital signs and other physiologicalmeasurements. Electrical Bioimpedance (EBI) is a non-invasive and effective technology that canbe used for detection and supervision of different health conditions. In some specific applicationssuch as body composition assessment EBIS has shown encouraging results proving good degreeof effectiveness and reliability. In a similar way Impedance Cardiography (ICG) is anothermodality of EBI primarily concerned with the determination of Stroke Volume SV, indices ofcontractility, and other aspects of hemodynamics.EBI technology in the previously mentioned modalities can benefit from a integration with agarment; however, a successful implementation of EBI technology depends on the goodperformance of textile electrodes. The main weakness of Textrodes is a deficient skin-electrodeinterface which produces a high degree of sensitivity to signal disturbances. This sensitivity canbe reduced with a suitable selection of the electrode material and an intelligent and ergonomicgarment design that ensures an effective skin-electrode contact area.This research work studies the performance of textile electrodes and garments for EBIspectroscopy for Total Body Assessment and Transthoracic Electrical Bioimpedance (TEB) forcardio monitoring. Their performance is analyzed based on impedance spectra, estimation ofparameters, influence of electrode polarization impedance Zep and quality of the signals using asreference Ag/AgCl electrodes. The study includes the analysis of some characteristics of thetextile electrodes such as conductive material, skin-electrode contact area size and fabricconstruction.The results obtained in this research work present evidence that textile garments with a dry skinelectrodeinterface like the ones used in research produce reliable EBI measurements in bothmodalities: BIS for Total Body Assessment and TEB for Impedance Cardiography. Textiletechnology, if successfully integrated, may enable the utilization of EBI in both modalities andconsequently implementing wearable applications for home and personal health monitoring. / <p>QC 20121213</p>

Neurologically related injuries cause a similar number of deaths ascancer, and brain damage is the second commonest cause of death in theworld and probably the leading cause of permanent disability. Thedevastating effects of most cases of brain damage could be avoided if itwere detected and medical treatment initiated in time. The passiveelectrical properties of biological tissue have been investigated for almost acentury and electrical bioimpedance studies in neurology have beenperformed for more than 50 years. Even considering the extensive effortsdedicated to investigating potential applications of electrical bioimpedancefor brain monitoring, especially in the last 20 years, and the specificallyacute need for such non-invasive and efficient diagnosis support tools,Electrical Bioimpedance technology has not made the expectedbreakthrough into clinical application yet. In order to reach this stage inthe age of evidence-based medicine, the first essential step is todemonstrate the biophysical basis of the method under study. The presentresearch work confirms that the cell swelling accompanying thehypoxic/ischemic injury mechanism modifies the electrical properties ofbrain tissue, and shows that by measuring the complex electricalbioimpedance it is possible to detect the changes resulting from braindamage. For the development of a successful monitoring method, after thevital biophysical validation it is critical to have available the properelectrical bioimpedance technology and to implement an efficient protocolof use. Electronic instrumentation is needed for broadband spectroscopymeasurements of complex electrical bioimpedance; the selection of theelectrode setup is crucial to obtain clinically relevant measurements, andthe proper biosignal analysis and processing is the core of the diagnosissupport system. This work has focused on all these aspects since they arefundamental for providing the solid medico-technological backgroundnecessary to enable the clinical usage of Electrical Bioimpedance forcerebral monitoring.

By means of the analytical formula of specific impedance for the spherical cells in suspensionintroduced by Kenneth S. Cole in 1928, a bioimpedance simulator has been developed for thegeneration of specific impedance spectrums of suspension of cells. With the help of the simulatorthe user can obtain different impedance spectrums according with the biophysical parameters ofthe cell suspension. Then, generate different kind of plots in order to understand and interpret allthe resulting information.With the selection of different values and range of the biophysical parameters to obtain thespectrums, it is possible to simulate different kinds of physiological process and observe theirelectrical bioimpedance behaviour in a certain range of frequencies. The performance of thesimulator has been validated simulating Cellular Edema and Haemorrhage has been alsosimulated.