Development of Portable Diffuse Optical Spectroscopic Systems For Treatment Monitoring

The goal of this dissertation is to demonstrate the utility of portable, small-scale diffuse optical spectroscopic (DOS) systems for the diagnosis and treatment monitoring of various diseases. These systems employ near-infrared light (wavelength range of 650nm to 950nm) to probe human tissue and are sensitive to changes in scattering and absorption properties of tissues. The absorption is mainly influenced by the components of blood, namely oxy- and deoxy-hemoglobin (HbO2 and Hb) and parameters that can be derived from them (e.g. total hemoglobin concentration [THb] and oxygen saturation, StO2). Therefore, I focused on diseases in which these parameters change, which includes vascular diseases such as Peripheral Atrial Disease (PAD) and Infantile Hemangiomas (IH) as well as musculoskeletal autoimmune diseases such as Rheumatoid Arthritis (RA). In each of these specific diseases, current monitoring techniques are limited by their sensitivity to disease progression or simply do not exist as a quantitative metric. As part of this project, I first designed and built a wireless handheld DOS device (WHDD) that can perform DOS measurements at various tissue depths. This device was used in a 15-patient pilot study for infantile hemangiomas (IH) to differentiate diseased skin from normal skin and monitor the vascular changes during intervention. In another study, I compare the ultra-small form- factor WHDD’s ability to monitor synovitis and disease progression during a patient’s treatment of RA against the capabilities of a proven frequency domain optical tomographic (FDOT) system that has shown to differentiate patients with and without RA. Learning from clinical utility of the WHDD from these two studies, I adapted the WHDD technology to develop a compact multi- channel DOS measurement system to monitor perfusion changes in the lower extremities before and after surgical intervention for patients with peripheral artery disease (PAD). Using this multi- channel system, which we called the vascular optical spectroscopic measurement (VOSM) system, our group conducted a 20-subject pilot study to quantify its ability to monitor blood perfusion before and after revascularization of stenotic arteries in the lower extremities. This proof-of- concept study demonstrated how DOS may help vascular surgeons perform revascularization procedures in the operating room and assists in post-operative treatment monitoring of vascular diseases

Mobile Health Technologies

Mobile Health Technologies, also known as mHealth technologies, have emerged, amongst healthcare providers, as the ultimate Technologies-of-Choice for the 21st century in delivering not only transformative change in healthcare delivery, but also critical health information to different communities of practice in integrated healthcare information systems. mHealth technologies nurture seamless platforms and pragmatic tools for managing pertinent health information across the continuum of different healthcare providers. mHealth technologies commonly utilize mobile medical devices, monitoring and wireless devices, and/or telemedicine in healthcare delivery and health research. Today, mHealth technologies provide opportunities to record and monitor conditions of patients with chronic diseases such as asthma, Chronic Obstructive Pulmonary Diseases (COPD) and diabetes mellitus. The intent of this book is to enlighten readers about the theories and applications of mHealth technologies in the healthcare domain

Diffuse Optical Imaging for Monitoring Peripheral Arterial Disease Revascularizations

Peripheral arterial disease (PAD) affects approximately 200 million individuals worldwide. It is characterized by a reduction in blood flow to the lower extremities due to atherosclerosis. This can result in leg pain, tissue loss, and ultimately amputation. Revascularization procedures aim to restore blood flow, but up to 50% of patients require another intervention within a year. Revascularization monitoring and early detection of failure are crucial in preventing limb loss and adverse cardiovascular events. However, current evaluation methods do not directly measure perfusion and are limited in a significant segment of PAD patients, such as those with diabetes and renal insufficiency. Diffuse optical imaging (DOI) techniques are promising tools to overcome these limitations. Employing near-infrared light, they are non-invasive, non-ionizing, contrast-free, and cost-effective methods that are sensitive to hemodynamic parameters such as changes in oxy-, deoxy-, and total hemoglobin concentration, making DOI ideal for revascularization monitoring. In this dissertation, I investigate and develop DOI systems for the purpose of monitoring lower extremity revascularization procedures in PAD patients. We utilize a contact-based diffuse optical spectroscopy (DOS) system to monitor localized foot perfusion in an ongoing clinical study of 100 patients undergoing lower extremity angiography. I demonstrate the utility of DOS measurements to provide valuable insights into revascularization related hemodynamic remodeling and to predict revascularization success. Furthermore, I also develop a clinic friendly contact-free diffuse optical tomography (DOT) system that is better-suited for PAD patients with ulcers. I show that this system can provide spatial maps of perfusion within the foot. Collectively, this work establishes diffuse optical imaging as a valuable imaging modality for the evaluation of lower extremity perfusion

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

The design and evaluation of discrete wearable medical devices for vital signs monitoring

The observation, recording and appraisal of an individual’s vital signs, namely temperature, heart rate, blood pressure, respiratory rate and blood oxygen saturation (SpO2), are key components in the assessment of their health and wellbeing. Measurements provide valuable diagnostic data, facilitating clinical diagnosis, management and monitoring. Respiratory rate sensing is perhaps the most under-utilised of all the vital signs, being routinely assessed by observation or estimated algorithmically from respiratory-induced beat-to-beat variation in heart rate. Moreover there is an unmet need for wearable devices that can measure all or most of the vital signs. This project therefore aims to a) develop a device that can measure respiratory rate and b) develop a wearable device that can measure all or most of the vital signs. An accelerometer-based clavicular respiratory motion sensor was developed and compared with a similar thoracic motion sensor and reference using exhalatory flow. Pilot study results established that the clavicle sensor accurately tracked the reference in monitoring respiratory rate and outperformed the thoracic device. An Ear-worn Patient Monitoring System (EPMS) was also developed, providing a discrete telemonitoring device capable of rapidly measuring tympanic temperature, heart rate, SpO2 and activity level. The results of a comparative pilot study against reference instruments revealed that heart rate matched the reference for accuracy, while temperature under read (< 1°C) and SpO2 was inconsistent with poor correlation. In conclusion, both of the prototype devices require further development. The respiratory sensor would benefit from product engineering and larger scale testing to fully exploit the technology, but could find use in both hospital and community-based The design and evaluation of discrete wearable medical devices for vital signs monitoring DG Pitts ii Cranfield University monitoring. The EPMS has potential for clinical and community use, having demonstrated its capability of rapidly capturing and wirelessly transmitting vital signs readings. Further development is nevertheless required to improve the thermometer probe and resolve outstanding issues with SpO2 readings

Recent trends in smartphone-based detection for biomedical applications: a review

Smartphone-based imaging devices (SIDs) have shown to be versatile and have a wide range of biomedical applications. With the increasing demand for high-quality medical services, technological interventions such as portable devices that can be used in remote and resource-less conditions and have an impact on quantity and quality of care. Additionally, smartphone-based devices have shown their application in the field of teleimaging, food technology, education, etc. Depending on the application and imaging capability required, the optical arrangement of the SID varies which enables them to be used in multiple setups like bright-field, fluorescence, dark-field, and multiple arrays with certain changes in their optics and illumination. This comprehensive review discusses the numerous applications and development of SIDs towards histopathological examination, detection of bacteria and viruses, food technology, and routine diagnosis. Smartphone-based devices are complemented with deep learning methods to further increase the efficiency of the devices. [Figure not available: see fulltext.] © 2021, The Author(s)

Certified Registered Nurse Anesthetist Performance and Perceptions: Use of a Handheld, Computerized, Decision Making Aid During Critical Events in a High-fidelity Human Simulation Environment

With the increasing focus on patient safety and human error, understanding how practitioners make decisions during critical incidents is important. Despite the move towards evidence-based practice, research shows that much decision making is based on intuition and heuristics (“rules of thumb”). The purpose of this study was to examine and evaluate the methodologic feasibility of a strategy for comparing traditional cognition versus the use of algorithms programmed on a personal digital assistant (FDA) in the management of unanticipated critical events by certified registered nurse anesthetists (CRNAs). A combined qualitative-quantitative methodology was utilized. The quantitative element consists of a pilot study using a cross-over trial design. Two case scenarios were carried out in a full-scale, high fidelity, simulated anesthesia care delivery environment. Four subjects participated in both scenarios, one without and one with a PDA containing a catalog of approximately 30 events with diagnostic and treatment related information in second scenario. Audio—videotaping of the scenarios allowed for definitive descriptive analysis of items of interest, including time to correct diagnosis and definitive intervention. The qualitative approach consisted of a phenomenological investigation of problem solving and perceptions of FDA use and the simulation experience by the participants using “think aloud” and retrospective verbal reports, semi-structured group interviews, and written evaluations. Qualitative results revealed that participants found the PDA algorithms useful despite some minor technical difficulties and the simulated environment and case scenarios realistic, but also described feelings of expectation, anxiety, and pressure. Problem solving occurred in a hypothetico-deductive manner. More hypotheses were considered when using the PDA. Time to correct diagnosis and treatment varied by scenario, taking less time with the PDA for one but taking longer with the PDA for the other, likely due to differences in pace and intensity of the two scenarios. The methodologic investigation revealed several areas for improvement including more precise control of case scenarios. All participants agreed with the value of using high fidelity simulation, particularly for problem solving of critical events, and provided useful information for more effective utilization of this tool for education and research

Development of a Wheelchair Seat Cushion with Site-Specific Temperature Control for Pressure Ulcer Prevention

Pressure ulcers are prevalent and costly, particularly for individuals with impaired mobility and sensation. They are primarily caused by high pressure near bony prominences. Multiple other factors include shear force, friction, temperature, and moisture. Recent research at the University of Pittsburgh was conducted on local cooling effects with respect to skin blood flow. A reduction of skin temperature to 25°C provided a significant benefit to local tissue in healthy controls and subjects with spinal cord injuries. This concurs with prior animal studies which demonstrated reductions in breakdown at lower interface temperatures. Pressure ulcers have been historically managed by providing support surfaces, such as wheelchair seat cushions, to redistribute pressure at the body interface. Few practical interventions exist to control temperature at this interface; most employ passive cooling methods, which are limited by their inability to modulate applied cooling in response to changes in microenvironment. This study's goal was to develop tightly controlled, local cooling elements for integration into a pressure-redistributing support surface. A holistic view of temperature control methods in an iterative design process was taken. Features, benchmarks, and design specifications were generated using available information from the literature. Idea generation and subsequent evaluation led to the modification of a multi-cell air cushion capable of controlling temperature in specific high risk areas. Proof of concept experiments were conducted with respect to interface cooling to a target temperature, redistribution of pressure, and heat and water vapor transmission. The design delivered local cooling over hour-long trials on able-bodied test subjects. No significant difference in skin temperature (p>0.16) was found after 15 minutes of cooling from our target temperature (25°C). The modified cushion showed similar (p=0.79) peak pressure index values when compared to the same cushion design without the cooling elements. A thermodynamic rigid cushion loading indenter mimicked the environmental conditions of the body on our prototype for 3-hour duration tests. Significantly lower temperatures were observed after 1 hour of cooling (p<0.003). No effect was noted for relative humidity. These experiments successfully demonstrated plausible, integrated cooling elements in a multi-cell air cushion for the delivery of local cooling for pressure ulcer prevention

Sensor Systems for Impaired Healing Markers, Concepts and Applications for Objective Wound Assessment

In the pathological healing of chronic wounds the ordered sequence of tissue restoration is disturbed. As a consequence, chronic wounds fail to heal within months and pose a major impact on the patient by pain, odor, leakage, and the risk of infection and the health care system by its constant treatment. Introducing objective wound assessment by sensor technology into clinical routine would help to guide treatment procedures and improve the healing outcome. The aim of this research study was the development of simple and effective concepts to evaluate the wound status at the point of care. Requirements for point of care testing include a fast and flexible device use by untrained personal, reduced time and costs, as well as reliable and easy to interpret results. The complex nature of wounds can be divided into the different regimes of physical appearance, biochemical status and microbiological environment, which influence each other. Each regime is tackled separately in this work by identifying possible parameters for wound analysis from the literature and the design of sensor concepts to quantify these candidates. A miniaturized, wearable sensor system for the integration in a wound dressing was developed to collect healing relevant, physiological data. The sensor measures optical reflectance, heart rate, arterial oxigenation, surface pH, moisture and temperature. The function of the sensor system was verified in a porcine wound model. A combination of surface pH, reflected infrared, and red light showed to be the most significant parameter, associated with the healing progress. For the measurement of biochemical parameters a microfluidic platform for the preparation of biosensing hydrogels by in situ polymerization was designed. Introducing functional structures for gel patterning in the chip fabrication allows for rapid assay customization. Simple handling and functionality were illustrated by assays for matrix metalloproteinase, an important factor in chronic wound healing. In addition, the demonstrated assays for total protein concentration and cell counts indicate the possibilities for a wide range of fast and simple diagnostics. The last part of the thesis discusses microfluidic technologies for rapid analysis of bacteria. Preconcentration of bacteria by on-chip electrophoresis and detection by a simple optical setup are presented. Furthermore, devices for rapid and parallel growth-based bacterial identification and antibiotic testing in microfluidic cultures were designed. The presented results and demonstrated tools show that medical analysis can be improved by sensor technologies that are simple to operate and yield fast results at the point of care