The principal aim of this work is to test the viability of Blood Oxygenation Level Dependent (BOLD) measurements in human myocardium, an experiment which has seen promising attempts in recent literature. A central challenge to the ~uccess of these experiments has been in the limited scale of the measured effect; this work therefore includes efforts to separate the BOLD effect from noise and confounding signals. BOLD is then measured by intensity in MR images produced using Steady State Free Precession (SSFP) acquisition, weighted by a T2 preparation module to introduce the target contrast. Two modelling sections are included: first, the changes in physiology which influence the signal intensity in the MR images via the T2 dependence; and secondly the factors upon which the preparation depends, which are not entirely limited to the T2 of the tissue. These models are investigated with the aim of increasing the BOLD contrast and removing any other dependencies. An empirical model is shown to be suitable for the relationship between oxygenation and T2, and improvements are suggested and explained by thorough simulation ofthe preparation module. Compensation for a further confounding effect is also investigated: that of the increase in heart rate which accompanies the adenosine infusion used in the BOLD experiment protocol to reveal differences in the response of ischaemic and healthy tissue. The compensation is shown to reduce temporal variance in SI measurements, and to increase the separation between distributions of SI in tissue classes. A process of registration and segmentation is refined for sampling BOLD information from the SS FP images, and tested to show a low failure rate. Finally, the BOLD process is then tested in a set of human subjects including healthy volunteers and patients with coronary artery disease, investigating the consequent difference in tissue oxygenation. A significant difference is shown in the responses to stress of BOLD SI three tissue classes in these subjects.

The ligands 2-(bis(2-(octahydro-2-oxobenzo[b][1,4]oxazin-4-yl)ethyl)amino)acetic acid trihydrochloride and bis(2-(octahydro-2-oxobenzo[b][1,4]oxazin-4-yl)ethyl)amine trihydrochloride are synthesized for the formation of Gd(III) complexes, potentially useful as MRI contrast agents. Speciation and hydration numbers of the Gd(III) complexes of 1,7- bis(2-hydroxycyclohexyl)-1,4,7-tris(carboxymethyl)-1,4,7-triazaheptane (Cy2DETA.3A) and 1,7-bis(2-hydroxycyclohexyl)-1,7-bis(carboxymethyl)-1,4,7-triazaheptane (Cy2DETA.2A) can be inferred from spectroscopic studies of the analogous Eu(III) complexes, due to their similar ionic radii, charge and coordination geometry. The phosphorescence emission spectra for the Eu(III) complexes are recorded as function of pH, in buffered and aqueous media. Modulation of the relative intensities of the emission bands is observed for both Eu(III) complexes. Spectroscopically determined pKa values are used to determine potential solution speciation. Ligand pKa values were determined potentiometrically. Attempts were made to correlate results from potentiometric titrations with that of lanthanide luminescent titrations of these complexes. Hydration states (q) were determined for the Eu(III) complexes at spectroscopically significant pH values, in buffered and aqueous media. The results confirm the formation of a octadentate complex between Eu(III) and Cy2DETA.3A, with the inclusion of one H2O molecule in the inner sphere. The complex has high stability and is responsive towards changes in pH and analyte concentration (o-phthalate); potentially suitable as a luminescent sensor. The heptadentate complex formed between Cy2DETA.2A and Eu(III) is substantially weaker, with precipitation of Eu(OH)3 observed at neutral pH, that limits its potential application as a luminescent sensor.

by Wong Mui Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 41-48). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.2 / TABLE OF CONTENT --- p.3 / LIST OF TABLES --- p.4 / LIST OF FIGURES --- p.5 / ABSTRACT --- p.6 / ABSTRACT (CHI) --- p.7 / Chapter CHAPTER 1 --- PROCESSING OF SPEECH IN CHINESE CHILDREN WITH DIFFERENT READING ABILITIES: AN FMRI STUDY --- p.8 / Chapter CHAPTER 2 --- METHOD --- p.18 / Participants --- p.18 / Imaging Technique --- p.18 / Other Apparatus --- p.18 / Procedure --- p.19 / Testing --- p.19 / Data Analysis --- p.22 / Chapter CHAPTER 3 --- RESULTS --- p.23 / Behavior data --- p.23 / Functional MRI data-group data --- p.24 / Functional MRI data-individual data --- p.32 / Chapter CHAPTER 4 --- DISCUSSION --- p.36 / REFERENCES --- p.41 / APPENDIX 1 --- p.49

"This research concentrates on two major engineering areas associated with biomedical instrumentation that have recently gained significant academic and industrial interest: the gradient coil design for Magnetic Resonance Imaging (MRI) and the high frequency full-wave field simulations with the Method of Moments (MoM). A new computational approach to the design of gradient coils for magnetic resonance imaging is introduced. The theoretical formulation involves a constrained cost function between the desired field in a particular region of interest in space and the current-carrying coil plane. Based on Biot-Savart’s integral equation, an appropriate weight function is introduced in conjunction with linear approximation functions. This permits the transformation of the problem formulation into a linear matrix equation whose solution yields discrete current elements in terms of magnitude and direction within a specified coil plane. These current elements can be synthesized into practical wire configuration by suitably combining the individual wire loops. Numerical predictions and measurements underscore the success of this approach in terms of achieving a highly linear field while maintaining low parasitic fields, low inductance and a sufficient degree of shielding. Experimental results confirm the field predictions of the computational approach. Extending the numerical modeling efforts to dynamic phenomena, a novel MoM formulation permits the computation of electromagnetic fields in conductive surfaces and in three-dimensional biological bodies. The excitation can be provided with current loops, voltage sources, or an incident electromagnetic wave. This method enables us to solve a broad spectrum of problems arising in MRI: full-wave RF coil simulations, eddy currents predictions in the magnet bore, and induced currents in the biological body. Surfaces are represented as triangles and the three-dimensional bodies are subdivided into tetrahedra. This numerical discretization methodology makes the approach very flexible to handle a wide range of practical coil geometries. Specifically, in this thesis the MoM is employed to study the effect of switching gradient coils in the presence of a biological load. "

A new method for the simulation of radio frequency (RF) coils has been developed. This method utilizes the FEM simulation package Ansoft HFSS as a base for the modeling of RF coils with complex biological loading effects. The abilities of this software have been augmented with custom MATLAB code to enable the fast prediction of lumped element values needed to properly tune and match the coil structure as well as to perform the necessary post processing of simulation data in order to quickly generate and evaluate field data of the resonating coil and compare design variations. This method was evaluated for accuracy and implemented in the re-design of an existing four channel breast coil array for clinical imaging of the female breasts. Based on the simulation results, a commercially viable printed circuit board (PCB) implementation was developed and tested in a clinical 1.5 T MR scanner. The new design allows for wide open bilateral access to the breast regions in order to accommodate various interventional procedures. The layout has also increased axillary B1 field coverage with minor penalty to the signal-to-noise ratio of the coil array, enabling high-resolution imaging over a wide field-of-view.

Magnetic Resonance Imaging (MRI) is a non-invasive procedure used in the medical community as a powerful way of creating images of the human anatomy. MRI is preferred over other examination techniques such as X-ray computed tomography (CT) because of its excellent soft tissue discrimination as well as the absence of ionizing radiation. Currently most clinical MRI systems use the single radio frequency coil imaging. However over past several years research has increasingly focused on the concept of using arrays of mutually decoupled surface coils. These surface coil arrays can simultaneously acquire multiple images, resulting in an increase in the field of view. This thesis pursues the design and construction of a high impedance preamplifier with the goal of investigating the decoupling of a surface coil array in a 4.7T magnetic resonance system.

雖然由老化引發的腦白質病變是老年人認知障礙的一個重要誘因，其機理缺並不為人所知。最新的小樣本研究表明擴散核磁造影在很大程度上是對腦白質病變最為敏感的的成像檢測手段。加深對擴散核磁造影所給出的各種指數的理解和認知對於檢測腦白質病變的病理發展以及研發試驗療法的替代標記有重要的意義。 / 為了獲得更具有臨床價值的擴散核磁造影指數，我們首先需要重構腦白質纖維束並沿著重構出的腦白質纖維束採集數值。然而，傳統的腦白質纖維束重構技術對於腦白質病變十分敏感。此外，不同病人所重構出的腦白質纖維束間缺乏映射關係也使我們無法有效進行大樣本統計分析。 / 在這個課題裡，我們提出了一個可以解決以上問題的一個全新框架。我們將專家標註過功能區的全腦白質纖維束模板配準到各個個體的腦部。此方案可自動生成個體化的全腦白質纖維束以及纖維束的功能區標註。自由形變模型被用於在全局層面對配準進行約束。所重構纖維束的曲率被用於在局部對配準進行約束。為了減輕腦白質病變對配準的影響，我們運用了一種 魯棒的主成分分析手段來檢測被病灶所干擾的纖維束。為了指導這些被干擾纖維束的配準，我們提出了一種全新的沿纖維束的區域特徵作為替代。此外，我們也探究了通過在纖維束上建立坐標系來除去離群纖維已經提供更高相關性的辦法。 / 我們所提出的框架被運用於一個腦小血管病變的臨床研究。在64個研究對象中約半數是腦白質病變患者。試驗結果證實此算法成功地將全腦白質纖維束模板配準到了所有研究對象上。沿著特定纖維束改採集的指數與認知測試分數的相關性顯著地超越了傳統指數所給出的結果。我們同時也發現沿著不同功能區腦白質纖維改採集的指數與相應的認知測試分數統計相關。 / Although age-related white matter lesion(WML)is an important substrate for cognitive impairment in the elderly, the mechanisms whereby WML induces cognitive impairment are uncertain. Recent findings based on small studies suggested that diffusion tensor imaging (DTI) measures might be the most sensitive imaging predictors in patients with WML. Understanding the imaging predictors for such disease will be useful in monitoring disease progression and in devising surrogate marker for treatment trials. / In order to obtain DTI measurements with diagnostic significance, it is first necessary to reconstruct the white-matter fiber pathways inside the brain along which certain DTI-derived values are calculated. Nevertheless, the traditional approach of white-matter tract reconstruction, or tractography, is severely hindered by the abundant existence of lesions inside the brains of WML patients. The lack of correspondence between fiber bundles across patients also makes obtaining group statistics of individual fiber bundles dicult. / In this study, we propose a novel framework that can mitigate the aforementioned issues of traditional tractography approaches. An expert-labeled whole brain tractography template is registered onto individual patients. Fiber trajectories and anatomically meaningful fiber bundles are automatically obtained by this registration. The free-form deformations are used to regularize the transformations at the whole brain level and across fiber bundles. Fiber curvatures are penalized as the intra-fiber regularization to encourage the smoothness of transformed fibers. White matter (WM) lesion is one of the major factors affecting tractography and registration of subjects with neuro Logical disorders. The Robust Principal Component Analysis(RPCA) is used to automatically detect fiber tract segments that are affected by WM lesion and a novel along-fiber regional prior is learned from healthy subjects to facilitate the registration of these fiber tract segments. We also propose to establish bundle-wise coordinate system by utilizing low-rank constraints upon the DTI measurements. The eort elevates the summary for an anatomical bundle from a scalar statistic to a vector containing changes along the representative fiber pathway. It provides means to exclude the outlier fibers while retaining partially-complete fibers. / The proposed scheme is applied to a clinical study of cerebral small vessel diseases(SVD).Experimental results show successful registration of the whole brain tractography template onto all 64 subjects, including both healthy con¬trol subjects and SVD patients. The DTI measures measured along specific registered anatomical fiber bundles exhibit significant boost in correlation with cognitive functions as compared with traditional measures. It also shows that different anatomical WM structures correlate with multiple types of cognitive functions in different ways. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / He, Xiaotian. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 46-53). / Abstracts also in Chinese. / List of Figures --- p.ix / List of Tables --- p.xii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Motivation --- p.1 / Chapter 1.2 --- Our Work and Contributions --- p.2 / Chapter 1.3 --- Related Work --- p.4 / Chapter 1.4 --- Thesis Organization --- p.5 / Chapter 2 --- Background --- p.6 / Chapter 2.1 --- Background of Neuroanatomy --- p.6 / Chapter 2.2 --- Background on Diffusion Tensor Magnetic Resonance Imaging (DTMRI) --- p.11 / Chapter 3 --- Free Form Fibers --- p.18 / Chapter 3.1 --- DTI Acquisition --- p.20 / Chapter 3.2 --- Fiber Model --- p.20 / Chapter 3.3 --- Fiber-to-DTI Registration --- p.21 / Chapter 3.3.1 --- Free-Form Fibers (FFFs) --- p.21 / Chapter 3.3.2 --- Tensor-Driven Fiber-to-DTI Registration --- p.23 / Chapter 3.3.3 --- Reliability Assessment by Robust Principal Component Analysis --- p.24 / Chapter 3.3.4 --- Contextual Feature --- p.26 / Chapter 3.3.5 --- Learning the Fiber Context Prior --- p.29 / Chapter 3.3.6 --- Registration Refinement Using the Fiber Context Prior --- p.29 / Chapter 4 --- Results --- p.31 / Chapter 5 --- Future Work --- p.39 / Chapter 5.1 --- Refinement on Large Bundles --- p.39 / Chapter 5.2 --- Outlier Fiber Removal in Fiber Template --- p.40 / Chapter 6 --- Conclusion --- p.44 / Bibliography --- p.46

by Gao Yibing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Local neuronal activity in the brain results in increased blood flow and is called neurovascular coupling. Such blood flow changes result in the blood-oxygen level dependent (BOLD) fluctuations detectable by functional magnetic resonance imaging (fMRI). The hemodynamic response is also an essential component of brain health and is impaired in various models of cognitive dysfunction. However, we still do not understand why functional hyperemia in the brain is important. To understand this question, various groups have studied brain metabolic activity as well as the mechanisms underlying neurovascular coupling. Over the years, several cell types have been proposed to contribute to functional hyperemia in the brain, including neurons, astrocytes and pericytes. However, the picture remains incomplete – controversies abound regarding the exact role of astrocytes, and pericytes in neurovascular coupling. Our lab has studies the mechanisms of neurovascular coupling from a mesoscopic perspective, as vasodilation in the rodent cortex involves capillaries and diving arterioles in the brain parenchyma as well as surface vasculature in the brain. We proposed that the vascular endothelium itself might provide a continuous conduit for transmitting vasodilatory signals initiated at the capillary level due to local neuronal activity. Given that systemic endothelial dysfunction could contribute to decreased neurovascular function, this hypothesis raised important concerns regarding endothelial vulnerabilities in common diseases like hypertension and diabetes and its role in diminished cognitive function and neurodegeneration. Based on findings from vascular research in other organ systems, we hypothesized that two distinct mechanisms of endothelium-derived vasodilation significantly contribute to neurovascular coupling the brain. These two mechanisms were expected to consist of fast long-range endothelium-derived hyperpolarization (EDH) dependent vasodilation (conducted vasodilation) and slower, more localized endothelium calcium-wave dependent vasodilation (propagated vasodilation). Together, we expected these mechanisms to shape the spatio-temporal evolution of hemodynamic responses in the brain. This dual mechanism of endothelial control of the hyperemic response in the brain might explain the complex spatiotemporal properties and non-linearities of the fMRI blood oxygen level dependent (BOLD) signal. My initial experiments were conducted in anesthetized rats, where I pharmacologically inhibited endothelial dependent vasodilation during functional hyperemia in the somatosensory cortex under a hind-paw electrical stimulus paradigm. While the results gleaned from these experiments were very revealing, it was important to consider the effect of the pharmacological manipulations on neuronal activity in the brain. In addition, neurovascular coupling and overall brain blood flow in anesthetized animals is dramatically altered when compared to awake animals. In order to accomplish these goals, I built a wide-field optical imaging system that could simultaneously measure fluorescence-based neuronal activity and reflectance-based hemodynamic activity in awake head-restrained mice. I then used non-blood brain barrier permeable pharmacology to study endothelial mechanisms of neurovascular coupling in awake Thy1-GCaMP6f mice, which express the calcium fluorophore in a subset of excitatory neurons in the cortex. I found that using this pharmacology I could dissect out the hypothesized two spatiotemporally distinct components of whisker-stimulus evoked neurovascular coupling in awake mice. With simultaneous recording of the neuronal activity driving this blood flow, I was able to build a mathematical model for neurovascular coupling that accounted for these two mechanisms by allowing for the superposition of a time-invariant, constant hemodynamic response with a hemodynamic response obtained by convolving the underlying neuronal response with a hemodynamic response function (HRF). I was able to linearize these apparent non-linearities in the hemodynamic response by studying the properties of deconvolved HRFs for stimuli of different durations before and after pharmacological manipulation of endothelial activity. Two important considerations remain. Firstly, our wide-field, mesoscopic view of the brain prevents observations of endothelial function (hyperpolarization and calcium activity) and the propagation dynamics of dilation best observed at the microscopic level. To accomplish this task, ongoing experiments currently use our high-speed volumetric imaging technology (SCAPE – Swept Confocally Aligned Planar Excitation microscopy) to study stimulus-evoked vascular dynamics in mouse lines expressing GFP and GCaMP8 in endothelial cells. Secondly, our longitudinal imaging of these animals is ideal for studying the acute and long-term effects of endothelial dysfunction on cognitive function. This requires adequate study of changes in mouse behavior during manipulations of endothelial function longitudinally in awake mice. Future experiments should involve the development and implementation of appropriate task-based behavior experiments, and analysis methods for more carefully exploring changes in neuronal activity in the mouse brain during stimulus and non-stimulus dependent activity.

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