Classification before regression for improving the accuracy of glucose quantification using absorption spectroscopy

This work contributes to the improvement of glucose quantification using near-infrared (NIR), mid-infrared (MIR), and combination of NIR and MIR absorbance spectroscopy by classifying the spectral data prior to the application of regression models. Both manual and automated classification are presented based on three homogeneous classes defined following the clinical definition of the glycaemic ranges (hypoglycaemia, euglycaemia, and hyperglycaemia). For the manual classification, partial least squares and principal component regressions are applied to each class separately and shown to lead to improved quantification results compared to when applying the same regression models for the whole dataset. For the automatic classification, linear discriminant analysis coupled with principal component analysis is deployed, and regressions are applied to each class separately. The results obtained are shown to outperform those of regressions for the entire dataset

Intelligent Remote Monitoring and Management system for Type1 Diabetes

The work presented in this thesis focuses on developing a telemedicine system for better management of type1 diabetes in children and teenagers. The research and development of the system is motivated by the inadequate communication in the current system of management of the disease, which results in non-compliance of patients following the regimen. This non-compliance generally results in uncontrolled blood glucose levels, which can result in hypoglycaemia, hyperglycaemia and later life health complications. This further results in an increase in health care costs. In this context, the thesis presents a novel end-to-end, low cost telemedicine system, WithCare+, developed in close collaboration between the University of Sheffield (Electronics & Electrical Engineering) and Sheffield Children’s Hospital. The system was developed to address the challenges of implementing modern telemedicine in type 1 diabetic care with particular relevance to National Health Service children’s clinics in the United Kingdom, by adopting a holistic care driven approach (involving all stakeholders) based on specific key enabler technologies such as low cost and reconfigurable design. However, one of the major issues with current telemedicine system is non-compliance of the patients due to invasive procedure of the glucose measurement which could be clearly addressed by non-invasive method of glucose measurement. Hence, the thesis also makes a contribution towards non-invasive glucose measurement using Near Infrared spectroscopy in terms of addressing the calibration challenge; two methods are proposed to improve the calibration of the Near Infrared instrument. The first method combines locally weighted regression and partial least square regression and the second method combines digital band pass filtering with support vector regression. The efficacy of the proposed methods is validated in experiments carried out in a non-controlled environment and the results obtained demonstrate that the proposed methods improved the performance of the calibration model in comparison to traditional calibration techniques such as Principal Component Regression and Partial Least Squares regression

Separating Signal from Noise in High-Density Diffuse Optical Tomography

High-density diffuse optical tomography (HD-DOT) is a relatively new neuroimaging technique that detects the changes in hemoglobin concentrations following neuronal activity through the measurement of near-infrared light intensities. Thus, it has the potential to be a surrogate for functional MRI (fMRI) as a more naturalistic, portable, and cost-effective neuroimaging system. As in other neuroimaging modalities, head motion is the most common source of noise in HD-DOT data that results in spurious effects in the functional brain images. Unlike other neuroimaging modalities, data quality assessment methods are still underdeveloped for HD-DOT. Therefore, developing robust motion detection and motion removal methods in its data processing pipeline is a crucial step for making HD-DOT a reliable neuroimaging modality. In particular, our lab is interested in using HD-DOT to study the brain function in clinical populations with metal implants that cannot be studied using fMRI due to their contraindications. Two of these populations are patients having movement disorders (Parkinson Disease or essential tremor) with deep brain stimulation (DBS) implants and individuals with cochlear implants (CI). These two groups both receive tremendous benefit from their implants at the statistical level; however, there is significant single-subject variability. Our overarching goal is to use HD-DOT to find the relationships between the neuronal function and the behavioral measures in these populations to optimize the contact location of these implant surgeries. However, one of the challenges in analyzing the data in these subjects, especially in patients with DBS, is their high levels of motion due to tremors when their DBS implant is turned off. This further motivates the importance of the methods presented herein for separating signal from noise in HD-DOT data. To this end, I will first assess the efficacy of state-of-the-art motion correction methods introduced in the fNIRS literature for HD-DOT. Then, I will present a novel global metric inspired by motion detection methods in fMRI called GVTD (global variance of the temporal derivatives). Our results show that GVTD-based motion detection not only outperforms other comparable motion detection methods in fNIRS, but also outperforms motion detection with accelerometers. I will then present my work on collecting and processing HD-DOT data for two clinical populations with metal implants in their brain and the preliminary results for these studies. Our results in PD patients show that HD-DOT can reliably map neuronal activity in this group and replicate previously published results using PET and fMRI. Our results in the CI users provide evidence for the recruitment of the prefrontal cortex in processing speech to compensate for the decreased activity in the temporal cortex. These findings support the theory of cognitive demand increase in effortful listening situations. In summary, the presented methods for separating signal from noise enable direct comparisons of HD-DOT images with those of fMRI in clinical populations with metal implants and equip this modality to be used as a surrogate for fMRI

BEst (Biomarker Estimation): Health Biomarker Estimation Non-invasively and Ubiquitously

This dissertation focuses on the non-invasive assessment of blood-hemoglobin levels. The primary goal of this research is to investigate a reliable, affordable, and user-friendly point-of-care solution for hemoglobin-level determination using fingertip videos captured by a smartphone. I evaluated videos obtained from five patient groups, three from the United States and two from Bangladesh, under two sets of lighting conditions. In the last group, based on human tissue optical transmission modeling data, I used near-infrared light-emitting diode sources of three wavelengths. I developed novel image processing techniques for fingertip video analysis to estimate hemoglobin levels. I studied video images creating image histogram and subdividing each image into multiple blocks. I determined the region of interest in a video and created photoplethysmogram signals. I created features from image histograms and PPG signals. I used the Partial Least Squares Regression and Support Vector Machine Regression tools to analyze input features and to build hemoglobin prediction models. Using data from the last and largest group of patients studied, I was able to develop a model with a strong linear correlation between estimated and clinically-measured hemoglobin levels. With further data and methodological refinements, the approach I have developed may be able to define a clinically accurate public health applicable tool for hemoglobin level and other blood constituent assessment

Development and application of novel processing tools and methods for cardiac optical mapping

Cardiac optical mapping provides unparalleled spatio-temporal resolution information of cardiac electrophysiology. It has hence emerged as an important technology in understanding cardiac electrical behaviour in physiological and pathophysiological states. There is a requirement for effective data analysis tools that are high-throughput, robustly characterised and flexible with regards to a growing array of experimental models. In this thesis a MATLAB based software, ElectroMap, was developed for analysis of diverse optical mapping datasets. ElectroMap incorporates existing and novel methods to allow quantification and mapping of action potential and calcium transient morphology and activation/repolarisation times. Automated pacing cycle length detection and segmentation were implemented, realising high-throughput analysis of beat-to-beat responses and transient behaviour. Standalone modules dedicated to calculation of conduction velocity and alternans were introduced, allowing thorough integration of key factors in arrhythmogenesis. Semi-automated analysis of temporal variations in wave morphology were developed from previous methodologies for electrogram analysis. Algorithms to use fractional rate of change of fluorescence as a measure of conduction were also introduced to the software. Algorithms were tested in silico datasets, mouse and guinea pig optical mapping datasets and preliminary experiments also showed use for in vivo human electrogram mapping of atrial fibrillation

Optical Gas Sensing: Media, Mechanisms and Applications

Optical gas sensing is one of the fastest developing research areas in laser spectroscopy. Continuous development of new coherent light sources operating especially in the Mid-IR spectral band (QCL—Quantum Cascade Lasers, ICL—Interband Cascade Lasers, OPO—Optical Parametric Oscillator, DFG—Difference Frequency Generation, optical frequency combs, etc.) stimulates new, sophisticated methods and technological solutions in this area. The development of clever techniques in gas detection based on new mechanisms of sensing (photoacoustic, photothermal, dispersion, etc.) supported by advanced applied electronics and huge progress in signal processing allows us to introduce more sensitive, broader-band and miniaturized optical sensors. Additionally, the substantial development of fast and sensitive photodetectors in MIR and FIR is of great support to progress in gas sensing. Recent material and technological progress in the development of hollow-core optical fibers allowing low-loss transmission of light in both Near- and Mid-IR has opened a new route for obtaining the low-volume, long optical paths that are so strongly required in laser-based gas sensors, leading to the development of a novel branch of laser-based gas detectors. This Special Issue summarizes the most recent progress in the development of optical sensors utilizing novel materials and laser-based gas sensing techniques

The application of neural networks to anodic stripping voltammetry to improve trace metal analysis

This thesis describes a novel application of an artificial neural network and links together the two diverse disciplines of electroanalytical chemistry and information sciences. The artificial neural network is used to process data obtained from a Differential Pulse Anodic Stripping (DPAS) electroanalytical scan and produces as an output, predictions of lead concentration in samples where the concentration is less than 100 parts per billion. A comparative study of several post analysis processing techniques is presented, both traditional and neural. Through this it is demonstrated that by using a neural network, both the accuracy and the precision of the concentration predictions are increased by a factor of approximately two, over those obtained using a traditional, peak height calibration curve method. Statistical justification for these findings is provided Furthermore it is shown that, by post processing with a neural network, good quantitative predictions of heavy metal concentration may be made from instrument responses so poor that, if using tradition methods of calibration, the analytical scan would have had to be repeated. As part of the research the author has designed and built a complete computer controlled analytical instrument which provides output both to a graphical display and to the neural network. This instrument, which is fully described in the text, is operated via a mouse driven user interface written by the author