Digital Image Processing And Metabolic Parameter Linearity To Noninvasively Detect Analyte Concentration

Spectroscopy is the scientific technique of quantifying and measuring electromagnetic, or light, reflectance or absorption. Atoms emit and/or absorb light when light passes through. The excitations provide specific energy signatures that relate to the element that is emitting or absorbing the light. Non-invasive biosensors monitor physical health properties such as heart rate, oxygen saturation, and tissue blood flow as a result of spectroscopy. Several attempts have been made to non-invasively detect metabolic chemical, or analyte, concentration with various spectroscopic techniques. The primary limitation is due to signal-to-noise ratio. This research focuses on a unique method that combines emission spectroscopy and machine learning to non-invasively detect glucose and other metabolic analyte concentrations. Artificial neural network is applied to train a predictive model that enables the remote sensing capability. The data acquisition requires capturing digital images of the spectral reflectance. Image processing and segmentation determines discrete variables that correlate with the metabolic analytes. The clinical trial protocol includes n=90 subjects, and a venipuncture comprehensive metabolic panel blood test within two minutes prior to a non-invasive spectral reading. Results indicate a strong correlation between the spectral system and the clinical gold standard, relative to metabolic analyte concentration

Wavelet Analysis of the Temporal Dynamics of the Laser Speckle Contrast in Human Skin

Objective: Spectral analysis of laser Doppler flowmetry (LDF) signals has been widely used in studies of physiological vascular function regulation. An alternative to LDF is the laser speckle contrast imaging method (LSCI), which is based on the same physical principle. In contrast to LDF, LSCI provides non-scanning full-field imaging of a relatively wide skin area and offers high spatial and temporal resolutions, which allows visualization of microvascular structure. This circumstance, together with a large number of works which had shown the effectiveness of temporal LSCI analysis, gave impetus to experimental studies of the relation between LDF and LSCI used to monitor the temporal dynamics of blood flow. Methods: Continuous wavelet transform was applied to construct a time-frequency representation of a signal. Results: Analysis of 10 minute LDF and LSCI output signals recorded simultaneously revealed rather high correlation between oscillating components. It was demonstrated for the first time that the spectral energy of oscillations in the 0.01-2 Hz frequency range of temporal LSCI recordings carries the same information as the conventional LDF recordings and hence it reflects the same physiological vascular tone regulation mechanisms. Conclusion: The approach proposed can be used to investigate speckle pattern dynamics by LSCI in both normal and pathological conditions. Significance: The results of research on the influence of spatial binning and averaging on the spectral characteristics of perfusion monitored by LSCI are of considerable interest for the development of LSCI systems optimized to evaluate temporal dynamics

Noninvasive Blood Flow and Oxygenation Measurements in Diseased Tissue

The research presented in this dissertation focused on the application of optical imaging techniques to establish blood flow and oxygen saturation as effective biomarkers for two disease cases, Autism Spectrum Disorder (ASD) and Huntington’s Disease (HD). The BTBR mouse model of ASD was utilized to validate measurements of cerebral blood flow and oxygenation as biomarkers for autism. The R6/2 mouse model of juvenile HD was utilized to validate measurements of skeletal muscle blood flow following tetanic muscle contractions induced by electrical nerve stimulation. Next, a noncontact, camera-based system to measure blood flow and oxygen saturation maps was implemented to improve upon the previous HD mouse results by providing spatial heterogeneity in a wild-type mouse model. Finally, translational research was performed to validate a research design conducting concurrent grip strength force and skeletal muscle blood flow and oxygenation measurements in a healthy human population that will be used to establish HD biomarkers in humans in future clinical applications

Investigation of Spatial Frequency Domain Imaging Analysis in Diabetic Foot Testing and Microneedle Treatments

Spatial Frequency Domain Imaging (SFDI) is a wide-field optical technique that utilizes spatially modulated selective wavelengths of light to probe biological tissue. Diffuse reflected light from the sample is compared to a table of values, extracted from a photon propagation simulation, to correlate experimental data to optical properties (absorption, scattering). The decoupling of absorption from scattering across multiple wavelengths allows for quantified chromophore content estimation within tissue. Biological chromophores are often associated with physiologic mechanisms and are key to quantifying disease progression. Exploration and verification of novel clinical utility of SFDI is essential for the potential benefit to medical outcomes of a variety of disease states and for adoption of the technology. In this work, the chromophore hemoglobin is used as a key metric for perfusion quality including total blood content in a region of interest and oxygen saturation. We aimed to test this technique in two new applications to add to the growing list of clinical research. Presented in this paper is a brief overview of SFDI, perfusion reactivity analysis of microneedle treatment, and a pilot study utilizing SFDI to analyze diabetic and neuropathic feet in several postural positions. Results from each previously mentioned use case indicate potential sensitivity to physiologic mechanisms such as pressure induced vasodilation, blood pooling, and vascular dysregulation. Additional research into postural regulation effects on perfusion of the diabetic foot is recommended as this pilot study indicated potential for neuropathic damage detection through perfusion metrics

Imaging photoplethysmography: towards effective physiological measurements

Since its conception decades ago, Photoplethysmography (PPG) the non-invasive opto-electronic technique that measures arterial pulsations in-vivo has proven its worth by achieving and maintaining its rank as a compulsory standard of patient monitoring. However successful, conventional contact monitoring mode is not suitable in certain clinical and biomedical situations, e.g., in the case of skin damage, or when unconstrained movement is required. With the advance of computer and photonics technologies, there has been a resurgence of interest in PPG and one potential route to overcome the abovementioned issues has been increasingly explored, i.e., imaging photoplethysmography (iPPG). The emerging field of iPPG offers some nascent opportunities in effective and comprehensive interpretation of the physiological phenomena, indicating a promising alternative to conventional PPG. Heart and respiration rate, perfusion mapping, and pulse rate variability have been accessed using iPPG. To effectively and remotely access physiological information through this emerging technique, a number of key issues are still to be addressed. The engineering issues of iPPG, particularly the influence of motion artefacts on signal quality, are addressed in this thesis, where an engineering model based on the revised Beer-Lambert law was developed and used to describe opto-physiological phenomena relevant to iPPG. An iPPG setup consisting of both hardware and software elements was developed to investigate its reliability and reproducibility in the context of effective remote physiological assessment. Specifically, a first study was conducted for the acquisition of vital physiological signs under various exercise conditions, i.e. resting, light and heavy cardiovascular exercise, in ten healthy subjects. The physiological parameters derived from the images captured by the iPPG system exhibited functional characteristics comparable to conventional contact PPG, i.e., maximum heart rate difference was <3 bpm and a significant (p < 0.05) correlation between both measurements were also revealed. Using a method for attenuation of motion artefacts, the heart rate and respiration rate information was successfully assessed from different anatomical locations even in high-intensity physical exercise situations. This study thereby leads to a new avenue for noncontact sensing of vital signs and remote physiological assessment, showing clear and promising applications in clinical triage and sports training. A second study was conducted to remotely assess pulse rate variability (PRV), which has been considered a valuable indicator of autonomic nervous system (ANS) status. The PRV information was obtained using the iPPG setup to appraise the ANS in ten normal subjects. The performance of the iPPG system in accessing PRV was evaluated via comparison with the readings from a contact PPG sensor. Strong correlation and good agreement between these two techniques verify the effectiveness of iPPG in the remote monitoring of PRV, thereby promoting iPPG as a potential alternative to the interpretation of physiological dynamics related to the ANS. The outcomes revealed in the thesis could present the trend of a robust non-contact technique for cardiovascular monitoring and evaluation

Optical Methods in Sensing and Imaging for Medical and Biological Applications

The recent advances in optical sources and detectors have opened up new opportunities for sensing and imaging techniques which can be successfully used in biomedical and healthcare applications. This book, entitled ‘Optical Methods in Sensing and Imaging for Medical and Biological Applications’, focuses on various aspects of the research and development related to these areas. The book will be a valuable source of information presenting the recent advances in optical methods and novel techniques, as well as their applications in the fields of biomedicine and healthcare, to anyone interested in this subject

Time domain, near-infrared diffuse optical methods for path length resolved, non-invasive measurement of deep-tissue blood flow

The non-invasive and, often, continuous measurement of the hemodynamics of the body, and for the main purposes of this thesis, the brain, is desired because both the instantaneous values and their changes over time constantly adapt to the conditions affecting the body and its environment. They are altered in pathological situations and in response to increased function. It is desirable for these measurements to be continuous, reliable, minimally invasive, and relatively inexpensive. In recent years, optical techniques that, by using diffusing and deep-reaching (up to few centimeters) light at skin-safe levels of intensity, combine the aforementioned characteristics, have increasingly become used in clinical and research settings. However, to date there is, on one side the need to expand the number and scope of translational studies, and, on the other, to address shortcomings like the contamination of signals from unwanted tissue volumes (partial volume effects). A further important goal is to increase the depth of penetration of light without affecting the non-invasive nature of diffuse optics. My PhD was aimed at several aspects of this problem; (i) the development of new, more advanced methods, i.e. the time/pathlength resolved, to improve the differentiation between superficial and deeper tissues layers, (ii) the exploration of new application areas, i.e. to characterize the microvascular status of bones, to study the functional response of the baby brain, and (iii) to improve the quality control of the systems , i.e. by introducing a long shelf-life dynamic phantom. In conceptual order, first I introduce long shelf-life reference standards for diffuse correlation spectroscopy. Secondly, I describe the use of an existing hybrid time domain and diffuse correlation spectroscopy system to monitor the changes that some pathological conditions, in this case osteoporosis and human immunodeficiency virus infection, may have on many aspects of the human bone tissue that are currently not easy to measure (i.e. invasively assessed) by conventional techniques. Thirdly, I describe the development of a novel time domain optical technique that intimately combines, introducing many previously unmet advancements, the two previously cited optical spectroscopy techniques. For the first time I was able to produce a time domain device and protocol that can monitor the blood flow in vivo in the head and muscles of healthy humans. Lastly, I describe a device and method that I have used to monitor changes in blood flow in healthy human infants of three to five months of age, for the first time in this age bracket, as a marker of activation following visual stimulation. Overall, this work pushes the limit of the technology that makes use of diffuse light to minimally invasively, continuously, and reliably monitor endogenous markers of pathological and physiological processes in the human body.La medición no invasiva y, a menudo, continua de la hemodinámica del cuerpo, y para los propósitos principales de esta tesis, del cerebro, es conveniente porque tanto los valores instantáneos como sus variaciones en el tiempo se adaptan constantemente a las condiciones que afectan el cuerpo humano y su entorno. Estas suelen alterarse en situaciones patológicas o como respuesta a una mayor función. Es deseable que estas mediciones sean continuas, confiables, mínimamente invasivas y relativamente asequibles. En los últimos años, las técnicas ópticas que, mediante el uso de luz difusa para medir los tejidos en profundidad (hasta unos pocos centímetros) mediante niveles de intensidad que son seguros para la piel, combinan las características arriba mencionadas, se han utilizado cada vez más tanto en entornos clínicos como de investigación. Sin embargo, al día de hoy hay, por un lado, la necesidad de ampliar el número y el ámbito de los estudios translacionales y, por el otro, de suplir a las deficiencias como por ejemplo la contaminación de volúmenes de tejido no deseados (efectos de volumen parcial). Otro objetivo importante es aumentar la profundidad de penetración de la luz sin afectar la naturaleza no invasiva de la óptica difusa. Mi doctorado está destinado a mejorar varios aspectos de este problema; (i) el desarrollo de nuevos métodos más avanzados, es decir, el método resuelto en el tiempo/trayectoria de los fotones, para mejorar la diferenciación entre los tejidos superficiales y profundos, (ii) la exploración de nuevas áreas de aplicación, es decir, para caracterizar el estado microvascular de los huesos, para estudiar la respuesta funcional del cerebro en los niños, y (iii) para mejorar el control de calidad de los sistemas, es decir, mediante la introducción de un phantom dinámico de larga vida útil. En orden conceptual, primero voy a introducir estándares de referencia de larga vida útil para la espectroscopia de correlación difusa (DCS). En segundo lugar, voy a describir el uso de un sistema híbrido espectroscopia tiempo-resuelta (TRS) con DCS ya existente para monitorizar los cambios que algunas condiciones patológicas, en este caso la osteoporosis y la infección por el virus de la inmunodeficiencia humana, pueden comportar para muchos aspectos del tejido óseo humano que actualmente no se pueden medir con facilidad (es decir, se van evaluado de forma invasiva) mediante técnicas convencionales. En tercer lugar, voy a describir el desarrollo de una novedosa técnica óptica en el dominio temporal que combina íntimamente, introduciendo muchos avances previamente no cumplidos, TRS y DCS. Por primera vez pude producir un dispositivo y un protocolo tiempo-resueltos para medir el flujo de la sangre en la cabeza y en los músculos de seres humanos sanos. Por último, en esta tesis voy a describir un dispositivo y un método que he usado para monitorear los cambios en el flujo sanguíneo como marcadores de activación del cerebro debida a estímulos visivos en bebés entre tres y cinco meses de edad. En general, este trabajo amplia los limites de la tecnología que hace uso de la luz difusa para monitorizar, de forma mínimamente invasiva, continua y confiable los marcadores endógenos de procesos patológicos y fisiológicos en el cuerpo humano.Postprint (published version