京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第21873号 / 人博第902号 / 新制||人||215(附属図書館) / 2018||人博||902(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 小松 直樹, 教授 加藤 立久, 准教授 廣戸 聡 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23070号 / 医博第4697号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 溝脇 尚志, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Formation of gas bubbles in complex fluids and their subsequent rise due to buoyancy is a very important fundamental phenomenon both in nature and industry. Bubble size and bubble velocity are critical parameters which govern the interfacial transport phenomena and play an important role in gas-solid contact. These characteristics affect the operating parameters as well as the design of equipment in industrial applications. Non-Newtonian, Shear-thickening fluids have been studied extensively due to their immense potential for commercial use in shock absorbing and force damping applications, such as liquid body armor, sports and personal protection. Furthermore, a better understanding of shear-thickening fluid is pertinent to industrial processing for enhancing flow, preventing the breakage or clogging of mixing equipment, and preventing clogging in narrow orifices. Despite their significance, many aspects of the flow of these non-Newtonian fluids remain poorly understood. In the first part of this dissertation, we study the dynamics of rising bubbles in three dimensional fluidized beds using computational fluid dynamics-discrete element method (CFD-DEM) to shed light on the physics underpinning phenomena uncovered previously using magnetic resonance imaging (MRI). We were able to understand the underlying mechanism behind the anomalous collapse of a bubble in side-by-side injection as well as an alternating asynchronous pinch-off pattern due to jet interaction in a fluidized bed by looking into the gas streamlines and the drag force on the particles. In the second part of this dissertation, we study dynamics of rising bubbles in Newtonian fluids and non-Newtonian cornstarch-water suspensions experimentally using optical imaging. We were able to identify that Capillary number (Ca) is a key dimensionless parameter governing the regimes of interacting jets in water. We also observed a periodic coalescence of bubbles at the same points in space in cornstarch-water suspensions and attributed this behavior to leading bubbles entering a shear thickening regime. Further, we identified the key dimensionless parameters for wobbling behavior of single bubbles in cornstarch suspensions to be Bond (Bo), and Reynolds (Re) number, regardless of the bubble being in a Newtonian or a shear-thinning regime. We believe our findings can be applied in industry to optimize the mass transport and liquid mixing for a range of applications.

Background. Major depressive disorder (MDD) is a leading cause of death and disability worldwide, and many individuals with MDD will experience treatment-resistant depression (TRD). TRD can lead to the development of suicidal ideation and behaviours, and up to 30% of people with refractory depression will attempt suicide at some point in their life. A neurobiological understanding of suicide is lacking, and neuroimaging markers of illness may elucidate the relationship between suicidal ideation and attempt. Diffusion tensor imaging (DTI) is a particularly sensitive neuroimaging modality that quantifies the microstructural integrity of white matter tracts, which may be useful in the investigation of psychiatric disease. The source of white matter changes may be further elucidated using free water imaging to isolate signal specific to the fibre tract and quantify the fractional volume of the free water compartment. Methodology. For this study, data were obtained from N=36 outpatients with TRD (n=20 suicide ideators and n=16 suicide attempters). Clinical characteristics of the patient sample were examined using clinician-rated and self-report questionnaires of depression and suicidal ideation severity. Whole-brain analysis of DTI data was conducted using tract-based spatial statistics (TBSS) via FMRIB Software Library (FSL) to identify between-group differences in white matter microstructure between suicide ideators and attempters. Free water imaging correction was applied through estimation of a constrained bi-tensor model via an in house MatLab-based script developed at Harvard University. Between-group differences of suicide ideators versus attempters were identified at a family-wise error (FWE) corrected significance threshold of p≤0.05. Subsequent exploratory analyses were performed at an uncorrected significance threshold of p≤0.01. Results. Suicide attempters had greater family history of suicide attempt, higher self-reported suicidal ideation severity, and were more likely to have received overnight treatment in a psychiatric facility in the past. TBSS revealed elevated mean diffusivity (MD), axial diffusivity (AD) and free water (FW) in suicide attempters compared to suicide ideators (thresholded p=<0.05, family-wise error corrected). Subsequent exploratory analyses revealed reduced fractional anisotropy (FA) and elevated radial diffusivity (RD) in fronto-thalamo-limbic white matter tracts of suicide attempters (thresholded p=<0.01, uncorrected). Free water correction appeared to increase detection of fractional anisotropy changes and suppress spurious differences in axial and radial diffusivity. Conclusion. The identification of significantly altered diffusion metrics in suicide attempters compared to suicide ideators suggests white matter pathology in TRD and suicide attempt. The effect of free water correction on diffusion metrics and the elevation of free water itself provide evidence toward the source of anisotropic changes. Future investigations to explore the combined impact of these measures in suicide and depression are recommended.

Thesis (MSc (Radiography))--Cape Peninsula University of Technology, 2019 / Introduction: Traumatic brain injury (TBI) is frequently associated with mortality and morbidity in low-income countries. Computed Tomography Brain (CTB) imaging aid in the management of patients by accurately exploring primary and secondary brain injuries following trauma. However, there is controversy among researchers on the benefits of follow-up CTB imaging (FCTBI) amongst patients presenting with TBI showing a normal baseline scan. As such, in an attempt to address the contention, the primary focus of this research study was to explore the role of FCTBI with regards to the clinical status of such patients. The secondary focus was to determine the timing of performing FCTBI post TBI. Method: A retrospective cross sectional quantitative design was conducted for this research study. A total sampling strategy was employed on medical records of 85 patients treated at the research site in Zimbabwe. Data were collected over a two year period. Adult patients between the ages of 18 and 75, with TBI and who had a normal first CTBI1 (primary scan done upon hospital admission) were included in this research study. The evolution of different types of brain pathology diagnosed on FCTBI in affected patients were recorded on data collection sheets. An analysis then followed to establish whether the sample patients had developed any neurological complications. Results: The study showed that in 85 patients with TBI, 36% recorded abnormal radiological findings on FCTBI with subdural haematoma (19%) being the most common intracranial lesion followed by intracerebral haemorrhage (8%), subarachnoid haemorrhage (6%) and lastly, pneumocephalus and epidural haematoma (1% respectively). The most frequent causal mechanism of trauma was road traffic accidents (RTAs) at 58%. Males with TBI comprised a higher proportion (53%) than did females (47%). The performance of CTBI1 at 8 hours post trauma occurrence, within a recommended hospital observation period of 20 hours post trauma occurrence, may provide sufficient time for lesions to evolve and thus determine the appropriate patient management. The young adult age group of 26-35 years was found to be more susceptible to TBI. Conclusion: FCTBI was found to be of value in timely detection of evolving intracranial lesions which enabled appropriate management of patients. The current study recommends that patients who exhibit a declining Glasgow Coma Scale (GCS) score and deteriorating neurological status undergo a FCTBI.

Lanthanide-based nanoparticles (Ln3+-based NPs) are promising candidates as magnetic resonance imaging (MRI) contrast agents. The present thesis aims to investigate the effect of the crystalline phase of Ln3+-based NPs on their MRI contrast performance. Understanding the phase-dependent MRI contrast behaviour of Ln3+-based NPs will provide insights into the development of brighter MRI contrast agents for future in vivo biomedical applications. A set of NaGdF4 NPs (6-8 nm) in cubic and hexagonal phases in the same size range was synthesized by employing a microwave-assisted approach, allowing the influence of host crystallinity on MRI T1 relaxivity to be investigated (chapter 4). The results showed that cubic NaGdF4 NPs exhibited superior performance as MRI T1 contrast agents than their hexagonal analogues, irrespective of the chosen surface modification, e.g. small citrate groups or longer chain poly(acrylic acid). NaDyF4 NPs (3 nm) were synthesized in both phases to assess whether phase-dependent MRI contrast behaviour consistently exists in other Ln3+-base NPs of the NaLnF4 family (chapter 5). Again, it was demonstrated that cubic NaDyF4 NPs had a better contrast performance as T2 contrast agents than the hexagonal NPs. Alternatively, cubic NaEuF4 NPs, exhibiting additional optical properties (e.g. red emission under UV excitation), were prepared as potential candidates for the preparation of chemical exchange saturation transfer (CEST) contrast agents (chapter 5). Chapter 6 introduces preliminary dispersion stability studies of cubic NaGdF4 NPs dispersed in different buffer solutions, the obtained hydrodynamic diameters indicated that NaGdF4 NPs possessed better dispersity in saline than that in PBS solution.

4 Title: Macrobicyclic ligands for use in MRI Author: Bc. Miroslav Pniok Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail address: modrej@natur.cuni.cz Abstract: The aim of this project is to synthesize new kind of macrobicyclic ligands for Ln3+ ions, especially Gd3+ ion. Gadolinium(III) complexes are widely used in the clinical practice as contrast agents for MR imaging and an improvement of their properties is in the center of interest of many scientific teams. The macrobicyclic ligands have been designed to make possible coordination of two water molecules in the first coordination sphere with fast water exchange. The macrocyclic core (cyclen) is combined with a linking phosphinate chain in N1 ,N4 - and N1 ,N7 -positions forming a cryptand-like structure. The N1 ,N7 -isomer Et2L1 was synthesized in a small amount so only the N1 ,N4 -isomer H2L3 has been studied. The protonation constants have been determined by pH 31 P NMR titration. Keywords: cyclen, chelating agent, cryptand, MRI, phosphinate

This document addresses the development and implementation of a routine for analyzing resting-state functional Magnetic Resonance Imaging (rs-fMRI) data in rodents. Even though resting-state connectivity is studied in humans already for several years with diverse applications in mental disorders or degenerative brain diseases, the interest for this modality is much more recent and less common in rodents. The goal of this project is to set an ensemble of tools in order to be able for the experimental MR team of KERIC to analyze rs-fMRI in rodents in a well defined and easy way. During this project several critical choices have been done, one of them is to use the Independent Component Analysis (ICA) in order to process the data rather than a seed-based approach. Also it was decided to use medetomidine as anesthesia rather than isoflurane for the experiments. The routine developed during this project was applied for a project studying the effects of running on an animal model of depression. The routine is composed of several steps, the preprocessing of the data mainly realized with SPM8, the processing using GIFT and the postprocessing which is some statistic tests on the results from GIFT in order to reveal differences between groups using the 2nd level analysis from SPM8 and the testing the correlations between components using the FNC toolbox. / Detta dokument behandlar utvecklingen och implementeringen av en rutin för att analysera bilder från resting-state funktionell Magnetisk Resonenstomografi i gnagare. Även om resting-state connectivity studerats i människor i några år, med olika applikationer i psykiska störningar och neurodegenerativa sjukdomar, är intresset för detta område är betydligt nyare bland experimentell förskare som arbetar med gnagare. Målet av denna projekt är att inställa en procedur så att KERICs experimentell MR team kan lätt analysera resting-state funktionnell MRT data. Under denna projekt har olika viktiga val gjorts, en av dem är att använda Independent Component Analysis procedur för att analysera data framför en seed-baserad teknik. En andra var att använda för anestesi medetomidin och inte isofluran för experiment. Rutinen som var utvecklad under denna projekt blev användad på data från en projekt som studerar effekter av löpning på depression hos råttorna. Rutinen är delad i några delar, den första är att förbehandla data främst med SPM8, den andra är att använda GIFT för att behandla data och den sista är att testa statistiskt resultat från ICA med SPM8 och att testa korrelation mellan komponenter med FNC.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) offer unique, noninvasive methods of measuring, respectively, in vivo quantitative neuroanatomy and neurochemistry. The main purpose of the present study was to identify and compare the neuroanatomical and neurochemical abnormalities that are associated with prenatal exposure to alcohol in both fetal alcohol syndrome (FAS)-diagnosed children and those diagnosed with fetal alcohol effects (FAE). MR data of three age-, gender- and race-balanced groups of children, FAS-diagnosed, FAE-diagnosed and non-exposed controls, were compared. Effects of prenatal alcohol exposure, regardless of diagnosis, were found in the caudate nucleus. Specifically, a significantly smaller caudate nucleus was found for the FAS and FAE participants compared to the controls. In addition, the metabolite ratio of N-acetyl-aspartate to creatine (NAA/Cr), an indicator of neuronal function, in left caudate nucleus of both the FAS and FAE participants was elevated compared to the control group. Analysis of absolute concentrations revealed that the increase in the ratio of NAA/Cr was due to an increase in NAA alone. Although its exact function in the CNS is unknown, NAA is believed to be a neuronal marker due to its exclusive localization to neurons. Some also speculate a role for NAA in myelination. Elevated NAA in the prenatal alcohol-exposed participants could indicate a lack of normal program cell death, dendritic pruning and/or myelination during development. The present study demonstrates that prenatal alcohol-exposed children, with or without facial dysmorphology, have abnormal brain anatomy and chemistry.