This dissertation describes the development, implementation, validation, optimization, and application, of a noninvasive and quantitative method for measuring cerebral blood volume changes with functional magnetic resonance imaging (fMRI) for mapping of neural activity changes. Since its inception over twenty years ago, the field of fMRI has grown in usage, sophistication, range of applications, and impact. Nevertheless it has yet to exploit its full potential regarding, spatiotemporal resolution, signal specificity, and quantifiability of hemodynamic changes. By utilization of a new MR pulse sequence, new concepts of radio frequency pulses, and high magnetic fields (7 T), a novel fMRI method named SS-SI VASO is presented here that overcomes sensitivity limitations of other noninvasive quantitative imaging methods. In order to validate that its signal represents changes in cerebral blood volume without other contaminations, SS-SI VASO is implemented in animal models for a close comparison with established, but invasive methods. A good agreement of blood volume sensitivity has been found with the new method compared to the established ones. After its validation, the SS-SI VASO method and its unprecedented sensitivity was used to localize and quantify hemodynamic changes in applications where conventional oxygenation based fMRI methods are limited. (A) SS-SI VASO was used to investigate biophysical aspects of actively controlled arteries and passive balloon-like veins during activity induced hemodynamic changes. (B) SS-SI VASO was used to provide insights whether the interplay of neural activity and resultant vascular response are the same for tasks that increase neural activity compared to tasks that suppress neural activity. (C) SS-SI VASO was used to calibrate conventional oxygenation based fMRI to quantify local changes in oxygen metabolism. (D) The high sensitivity of SS-SI VASO was further used to obtain sub-millimeter resolutions and estimate activity changes between cortical layers. This enables to address questions not only where the brain is activated but also how and whereby this activity is evoked. The implementation and application of this new SS-SI VASO fMRI method is a major step forward for the field of imaging neuroscience; it demonstrates that the current limitations of fMRI can be even overcome with respect to quantifiability, spatial specificity and distinguishing between vascular and neuronal phenomena.

Thesis (M.S.)--Ohio University, November, 2004. / Includes bibliographical references (p. 83-90)

Thesis (M.S.)--Brigham Young University. Dept. of Exercise Sciences, 2007. / Includes bibliographical references.

Thesis (M.S.)--Ohio University, November, 2004. / Title from PDF t.p. Includes bibliographical references (p. 83-90)

The importance of hypovolemia in dehydrational death was assessed in two anuran species. Xenopus laeyis, a species which experiences a significant reduction in circulating plasma volume with dehydration, was used to evaluate the role of sympathetic reflex compensation in hypovolemia. Adrenergic blockade with propranolol or phenoxybenzamine produced no significant reduction in dehydration tolerance in this species, although β-blockade with propranolol appeared to have a minor effect. The role of hypovolemic shock in the terminal circulatory collapse that precedes death in dehydrating anurans was investigated in the toad, Bufo marinus. The activity of lysosomal proteinases (cathepsins) was used as an indicator of the shock state. An assay was developed for the determination of cathepsin activity in toad plasma and was used to demonstrate the presence of proteinases similar in pH dependence to mammalian cathepsins Bl and D. Plasma cathepsin D-type activity increased with dehydration in toads but was not significantly different from the activity in controls or in toads subjected to splanchnic artery occlusion. Toads appear to maintain plasma volume to 20% water loss at the expense of other extracellular fluids. These results do not support the hypothesis that hypovolemia is a direct cause of dehydrational death in anurans.

Cardiovascular disease, including hypertension, accounts for almost 50% of the deaths in patients with end stage renal disease (ESRD) on hemodialysis (HD) yet hypertension remains very poorly controlled in this population. The purpose of this study was to retrospectively compare control of hypertension in hemodialysis (HD) patients when extracellular volume (ECV) was assessed and managed by clinical parameters and physical assessment data alone with control of hypertension when data from blood volume monitoring (BVM) technology was also used to assess and manage ECV in a freestanding outpatient hemodialysis unit. The main cause of hypertension in the ESRD population has been identified as increased ECV most likely secondary to increased interdialytic weight gain and failure to attain and maintain patient’s dry weight. HD nurses often employ clinical parameters along with physical examination to determine a patient’s pre, intra, and post dialytic fluid status and this approach can have a high index of error. BVM technology is being used in many hemodialysis units to assist with assessment of ECV. A comparative retrospective chart review was used to collect data for this project. A descriptive, cross-sectional design was employed to answer the question:“Are hypertensive hemodialysis patients who dialyze in a freestanding dialysis unit, where BVM technology is utilized, more likely to be normotensive as defined by a pre dialysis blood pressure of less than 140/90 and post dialysis blood pressure less than 130/80”? A pilot study was conducted to determine if the patient population and data were available in existing patient records for extrapolation. Approval for the study was obtained from the University IRB. A convenience sample was obtained from the records of patients meeting the inclusion criteria. Variables were measured and analyzed using iv descriptive statistics such as sampled paired T-test to compare pre and post BVM systolic, diastolic blood pressures, intradialytic weight gain, serum Albumin and sodium levels, and hemoglobin. A p-value of 0.05 was assigned for statistical significance. Data analysis showed there were statisticaly significant differences in the pre dialysis systolic blood pressure, post BVM, and the serum sodium pre and post BVM when the two groups were compared These statistically significant findings support a correlation between reduction in the HD patient’s ECV and improved blood pressure control. The reduction of pre-dialysis SBP was significant because many patients on hemodialysis have systolic hypertension that may or may not coexist with diastolic hypertension. The findings of this study may be used to formulate a protocol to be used in the HD units where the BVM is available. The protocol would rely on accurate nursing assessment of clinical parameters, patient verbalizations of symptoms, and the routine use of the BVM in order to continuously assess the patient’s fluid status. Future research recommendations include conducting the study in a population closer to the national sample, a study where glucose readings and /or hemoglobin A1C levels are measured to assess the impact of glucose on ECV, and which antihypertensive class of medication works best with BVM technology to effectively manage hypertension in this population.

This study examined the effects of blood extraction on the survival of horseshoe crabs and performed a preliminary investigation into amebocyte maintenance in vitro. Hemolymph volume of L. polyphemus was estimated over a representative size range of adults. Hemolymph volume expressed as a percentage of wet body weight was 25 ± 2.2% (mean ± S.D.) for males and 25 ± 5.1% for females. Mortality associated with blood extraction was evaluated for horseshoe crabs bled 0, 10, 20, 30, and 40% of their estimated hemolymph volume (unstressed group, N = 200). Mortality associated with the same bleeding levels was evaluated in horseshoe crabs that underwent simulated transport and handling procedures of the biomedical industry's bleeding process (stressed group, N = 195). Mortality rates of the unbled crabs were not significantly different between the stressed group and unstressed group. Of the bled animals, there was a higher (8.3%) mortality rate in the stressed group, than that (0%) in the unstressed group (P < 0.0001). Within the stressed group, mortality was significantly associated with bleeding (P = 0.0088). Horseshoe crab serum and a variety of standard insect cell culture media were evaluated for their effects on amebocyte morphology and viability after 7 days of maintenance in vitro. Horseshoe crab serum-supplemented cultures had significantly higher cell viability than serum-free cultures (N = 6; P = 0.0147). Significant differences in amebocyte viability were identified among the six insect cell culture media tested (N = 36; P < 0.0001), with the highest amebocyte viability of 77.2 ± 5.1% (mean ± S.D.) in Grace's Insect Medium without serum. Information gained from this study provides guidance on altering biomedical bleeding protocols to decrease horseshoe crab stress and mortality, and advances information on amebocyte culture medium selection, both of which contribute to decreasing the biomedical industry's impact on the horseshoe crab population. / Master of Science

Functional magnetic resonance imaging (fMRI) as it exists, in its many forms and vari- ants, has revolutionized the fields of neurology and psychology by revealing functional differences non-invasively. Although blood oxygenation level dependent (BOLD) fMRI is used interchangeably with fMRI, it measures one single difference in a phys- iological measurement using a set sequence. As such, there are other established changes in the brain that relate to blood movement and capacity that can also be measured using MRI. One measure, exogenous steady state cerebral blood volume, uses a bolus routine contrast agent administered intravenously alongside a pair of high resolution ‘structural-like’ MRI images to provide detailed information within small cortical and subcortical structures. In this thesis I design a semi-automated algorithm to generate maps of steady state exogenous cerebral blood volume magnetic resonance imaging datasets. To do this I developed an algorithm and tested it on existing MRI scanning protocols. A series of automated pre-processing steps are developed and tested, including automated scan flagging for artifacts and requisite vascular segmentation. Then, a methodology is developed to create cerebral blood volume (CBV) region of interest (ROI) masks that can then be applied on an existing database to test known CBV dysfunction in a group of patients at high risk for psychosis. Finally, we develop an experiment to see if template based cerebral blood alterations co-registered with class segmentation maps have any positive predictive value in determining disease state in a well characterized cohort of five age-matched groups in an Alzheimer’s disease neuroimaging study.

by Leung Chung-chu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 101-107). / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.iii / LIST OF ABBREVIATIONS --- p.iv / LIST OF PUBLICATIONS --- p.v / TABLE OF CONTENTS --- p.vi / Chapter CHAPTER 1 --- Introduction / Chapter 1.1 --- Background of the Rheopneumograph --- p.1 / Chapter 1.2 --- The Electrical Bio-impedance (EBI) technique used in Rheopneumography --- p.2 / Chapter 1.3 --- Problems with analysis of Rheopneumograph --- p.6 / Chapter 1.4 --- The EBI measurement unit --- p.8 / Chapter 1.5 --- Data analysis in Rheopneumography and the electrode design --- p.8 / Chapter 1.6 --- Modelling analysis in Rheopneumography --- p.9 / Chapter 1.7 --- Thesis outline --- p.10 / Chapter CHAPTER 2 --- Improvement to the impedance measurement system / Chapter 2.1 --- Introduction --- p.13 / Chapter 2.1.1 --- The Coherent Detection method in EBI signal --- p.13 / Chapter 2.1.2 --- To discuss the problem in Coherent Detection method --- p.16 / Chapter 2.1.3 --- To discuss the problem in Costas Receiver method --- p.16 / Chapter 2.2 --- The concept of the Amplitude Modulation Receiver --- p.17 / Chapter 2.3 --- EBI measurement unit design using AM receiver technique --- p.18 / Chapter 2.3.1 --- The C-Y receiver --- p.18 / Chapter 2.3.2 --- A simple DC offset adjust circuit --- p.23 / Chapter 2.3.3 --- 555KHz local oscillator and constant current source --- p.25 / Chapter 2.3.4 --- Selection of the low pass filter --- p.29 / Chapter 2.4 --- The characteristic of the whole circuit and performance --- p.32 / Chapter 2.5 --- Discussion --- p.36 / Chapter CHAPTER 3 --- Data analysis in Rheopneumogram / Chapter 3.1 --- Introduction --- p.38 / Chapter 3.2 --- The 5-10 electrode array method applied in Thorax Montage --- p.39 / Chapter 3.2.1 --- The definition of the 5-10 electrode array method --- p.39 / Chapter 3.2.2 --- The advantage of the 5-10 electrode array method --- p.41 / Chapter 3.3 --- Signal analysis in subject-to-subject comparison --- p.41 / Chapter 3.3.1 --- The relationship between the ECG and Rheopneumogram --- p.45 / Chapter 3.4 --- Identification of the best electrode location in Rheopneumograph using Pump-jet model --- p.51 / Chapter 3.4.1 --- The fluid mechanical model device (Pump-jet model) --- p.51 / Chapter 3.4.2 --- Result and discussion --- p.57 / Chapter 3.5 --- Electrical conductivity studies in Silicon fluid-Graphite composites applied in EBI electrode array system --- p.62 / Chapter 3.5.1 --- Experimental procedure and results --- p.63 / Chapter 3.6 --- Discussion --- p.73 / Chapter CHAPTER 4 --- Model analysis for the Impedance Rheopneumogram / Chapter 4.1 --- Introduction --- p.76 / Chapter 4.2 --- Blood flow phenomenon study in Rheopneumogram using Pipeline model --- p.78 / Chapter 4.2.1 --- Model derivation --- p.79 / Chapter 4.2.2 --- Result and discussion --- p.86 / Chapter 4.3 --- Blood velocity study in Rheopneumogram using Pump-jet model --- p.94 / Chapter 4.3.1 --- Result and discussion --- p.94 / Chapter 4.4 --- Conclusion --- p.96 / Chapter CHAPTER 5 --- General discussion and Conclusion --- p.97 / Chapter CHAPTER 6 --- Reference --- p.101 / APPENDICES / Chapter I --- Measurement method in the study --- p.107 / Chapter II --- The simplification of an equation in pump-jet model --- p.109 / Chapter III --- The simplification of an equation in pipeline model --- p.111 / Chapter IV --- Impedance relation between body and electrode --- p.112 / Chapter V --- The procedure of the curve fitting --- p.113

Wearable sensors can be used to monitor opioid use and other key behaviors of interest, and to prompt interventions that promote behavioral change. The effectiveness of such systems is threatened by the potential of a subject's deliberate non-compliance (DNC) to the monitoring. We define deliberate non-compliance as the process of giving one's device to someone else when surveillance is on-going. The principal aim of this thesis is to develop an approach to leverage movement and cardiac features from a wearable sensor to detect such deliberate non-compliance by individuals under surveillance for opioid use. Data from 11 participants who presented to the Emergency Department following an opioid overdose was analyzed. Using a personalized machine learning classifier (model), we evaluated if a snippet of blood volume pulse (BVP) and accelerometer data received is coming from the expected participant or an alternate person. Analysis of our classier shows the viability of this approach, as we were able to detect DNC (or compliance) with over 90% accuracy within 3 seconds of its occurrence.