Physiological system modelling and clinical simulation for diagnosis

Chapter 0 Contains the thesis introduction thesis and concepts of NDIs, derivations and applications. It also summarizes the PNDIs that are derived in the subsequent chapters. Chapter 1 Introduces the concept of using Physiological Non-Dimensional Indexes (PNDI) for distinguishing or classifying patients who were diabetic from non-diabetic and those who are the risk of becoming diabetic. In the authors work, he has also demonstrated that those who were diabetic were actually at-risk and those who were normal were in fact at the rim of becoming diabetic. All the works were verified against with clinical data by parametric identification techniques. Chapter 2 Using the findings of the above chapter, the author conceptualized, and design and simulated a dynamic activity-based insulin infusion system. He has used the clinical data of diabetic patients in the above chapter for demonstrating the operations of the system. He has even demonstrated the stability of the system by having continual simulations till 4-hour. Chapter 3 In this chapter, the author has derived a series of system equations for identification of pulmonary diseases based in the inhale and exhale gas mixtures concentrations and volume space. Chapter 4 In this chapter, the author has derived a series of system equations for identification of diseased lungs based of the lungs’ pressurevolume graphs. He has even demonstrated the techniques of obtaining the Cardiac Output (CO) non-invasively. Chapter 5 The author has demonstrated how to obtain the relative urine outflow non-invasively for normal kidneys. Chapter 6 The author has described the significance and derivation background of PNDI

Human retinal oximetry using spectral imaging

The principal aim of the research described in this thesis was to develop a technique of non-invasively measuring the oxygen saturation within the retinal vasculature of human subjects (retinal oximetry). The evaluation of a hyperspectral fundus camera used to acquire retinal images in different wavelengths of visible light, and the image analysis techniques used to perform retinal oximetry are described. Validation of the oximetry techniques was performed using an artificial eye containing human blood of known oxygen saturation: the calculated oxygen saturation was compared to the gold standard measurement. The mean differences between the calculated and measured oxygen saturations were small. Hyperspectral imaging/oximetry of normal subjects was performed to characterize the oximetric features of the retinal vasculature. The mean oxygen saturation (± SD) of the temporal retinal arterioles and venules were 110.8% (± 11.8%) and 27.7% (± 3.2%) respectively. The application of the retinal oximetry technique was explored in patients with retinal arterial and venous occlusion to determine whether oximetric changes in the retinal vasculature could be detected. Variation in measured oxygen saturation of the retinal arterioles and venules respectively were apparent, and corresponded with angiographic features of retinal capillary loss. The techniques were applied to patients with asymmetrical primary open angle glaucoma to determine whether oximetric changes could be detected. The mean oxygen saturation of the temporal retinal venules were significantly higher [44.8% (± 24.2%)] in the more advanced glaucomatous eyes compared to normal subjects. Hyperoxia of the retinal venules suggests reduced oxygen consumption as a consequence of inner retinal dysfunction in glaucoma. However, because of the small sample size, further research on a larger population of subjects is required to support this finding. Hyperspectral imaging could be used to detect oximetric abnormalities in the retinal vasculature in patients with retinovascular occlusion and glaucoma

A Comparative Study of the Pathology and Pathophysiology of Severe Malaria in a Non-Human Primate Model

With the rise in plasmodial drug resistance throughout the world, a dwindling arsenal of anti-malarials and a predilection for use of less than ideal murine models, the need for effective, applicable and established animal models through which to understand severe malarial disease and test potential treatments is becoming increasingly crucial. Plasmodium coatneyi was discovered in the Philippines in the early 1960s in Rhesus macaque monkeys and has been evaluated sporadically as a potential platform for comparative studies of Plasmodium falciparum induced severe and cerebral malaria in humans. Using 30 years worth of archival samples at the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, compounded with data and material from a series of prospective experimental studies, the work in this thesis sought to fully characterize and describe the pathology and pathobiology of the P. coatneyi/Rhesus macaque model. This included a thorough examination of the parasite host interaction, clinical symptomology, hematology and clinical pathology, gross pathology, histopathology, immunohistochemistry, cerebrospinal fluid cytokine profiles, transmission and scanning electron microscopy and atomic force microscopy of the disease in 45 adult rhesus macaques. The study further compared P. coatneyi with existing P. falciparum infected human material maintained at the National University of Singapore’s Vivax laboratory and Oxford University’s Ultrastructural Morphology Group, Nuffield Division of Clinical Laboratory Sciences. The study culminated in a successful clinical drug trial which evaluated the efficacy of varying doses of methylene blue as a radical cure for malaria in this non-human primate model. In many ways, the model mirrors P. falciparum, however the benefit of this evaluation is that it highlights not only the similarities but also the divergences. The successful completion of this description of the pathology and pathobiology of the P. coatneyi/Rhesus macaque model of severe and cerebral malaria adds a complex but effective animal model to the armamentarium in the ongoing war against malaria

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

Applications and Experiences of Quality Control

The rich palette of topics set out in this book provides a sufficiently broad overview of the developments in the field of quality control. By providing detailed information on various aspects of quality control, this book can serve as a basis for starting interdisciplinary cooperation, which has increasingly become an integral part of scientific and applied research

Clinical and radiological studies in PSP and related conditions

This thesis examines clinical and radiological aspects of Progressive Supranuclear Palsy (PSP) and related conditions. Significant milestones occur sooner in pathologically confirmed PSP than multiple system atrophy (MSA); older age of onset and shorter duration to first milestone are associated with worse prognosis in both; in PSP, the Richardson’s syndrome phenotype and male gender and in MSA, early autonomic failure and the female gender are also predictive of poorer prognosis. Using objective measurements of bradykinesia we found progressive bradykinesia and hypokinesia in Parkinson’s disease (PD) which correlates with disability and responds to levodopa but hypokinesia without decrement in PSP. Using conventional MRI 72.7% of PSP and 76.9% of MSA are correctly identified. The ‘hummingbird sign’ was highly specific for PSP, but sensitvity was 68.4%. A simple measurement of the midbrain < 9.35mm had 100% specificity for a pathological diagnosis of PSP. In a clinically diagnosed PSP 90.5% had a measurement of < 9.35mm. Using high field 9.4 Tesla MRI, the anatomy of the subthalamic nucleus is clearly defined when compared to histology in post mortem material. The anteromedial portion was hypointense in correlation with Perls stain and there was variability in the volume, shape and location of its borders. The nigrosomes within the substantia nigra were visibile as high intensity bands which correlated with calbindin poor zones on immunohistochemical stains. The volume and anatomy were preserved in PD but not PSP. Multimodal 3 Telsla MRI during life revealed distinct patterns of atrophy in PSP and MSA using voxel-based morphometry. Tract-based spatial statistics revealed abnormalities in the frontal and parieto-occipital white matter changes in PSP more than MSA. Midbrain atrophy and frontal white matter increased mean diffusivity were associated with increasing PSP rating scale score, and frontal white matter reduced fractional anisotropy with disease duration