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Myelin is a protein complex which plays an integral role in developing and maintaining proper brain function. Due to the plasticity of the brain, and the dynamic nature of myelin, it is critical to develop methods that allow for the investigation of changes in myelin in vivo, to further our understanding of the brain. A substantial amount of myelin is found in the grey matter (GM) of the cerebral cortex – the outermost structure of the brain that supports higher order functions including cognition and more fundamental functions, such as sensation and motor control. While in vivo investigations have traditionally used imaging to focus on myelin in the deep white matter (WM) tracts in the brain, advances in magnetic resonance imaging (MRI) are now allowing investigations of intracortical myelin (ICM). The research in this thesis presents methodology for investigating intracortical myelin levels using magnetic resonance imaging (MRI) in humans, with the aim of developing a better understanding of how myelin contributes to healthy cortical function, and how it may be disrupted in disease. To characterize intracortical myelin, a novel MRI analysis technique was developed early in this work to report the thickness of the heavily myelinated and lightly myelinated layers of the cortex. This measure of myelinated cortical thickness uses a clustering algorithm to separate the layers of the cortex based on voxel intensity in a T1- weighted (T1W) MRI with strong intracortical contrast. The resulting myelinated thickness maps match known myelin profiles of the brain, with cortical regions such as the primary visual and motor cortices displaying proportionally thicker, heavily myelinated layers. The utility of the myelinated cortical thickness for answering clinical questions was tested in bipolar disorder, where a preferential loss of the more myelinated layers in the dorsal lateral prefrontal cortex was found. This study provided the first in vivo evidence of ICM disruptions in bipolar disorder. Later in the thesis work, after surface-based analysis techniques became available, an alternative approach to investigate intracortical myelin was developed that sampled the T1W image intensity at a calculated depth of the cortex as a measure of myelin content. This methodology was used for studying the association of ICM with age in healthy adults ranging from late adolescence to middle-adulthood. It was found that three cortical depths followed a similar trajectory through this age-span, reaching their peak between 35 and 40 years of age. This study contributes to a picture of ICM amounts increasing well into middle age in healthy adults and provides a baseline for studies investigating how this may be disrupted in disease Up to this point, the analysis in the thesis used a specialized T1W MRI that had been optimized to provide strong intracortical contrast, but a question remained of how useful the technique would be if more commonly collected clinical MRIs were used as inputs. This analysis was thus applied to standard T1W and T2-weighted (T2W) anatomical MRIs to test its clinical applicability. 360 participants were investigated from the TRACK-HD dataset to test if intracortical signal analysis could follow the progression of Huntington’s disease. A significant increase in intracortical T1W/T2W signal was found in the most advanced disease group in several cortical regions. This increase in intracortical signal is likely tracking a known increase in iron and/or myelin levels in the Huntington’s disease brain. However, this work suggests that ICM studies would best be conducted with optimized imaging to better be able to characterize the subtle ICM variations within the GM. Overall, the work in this thesis presents two techniques for whole-brain mapping of the distribution of intracortical myelin using MRI. The clinical applicability of the techniques was demonstrated in examples of mental and neurodegenerative disorders. The future directions of this work include developing imaging specific to either myelin or iron as well as revisiting these problems while imaging at greater resolution to better characterize the laminar profile across the cortex. / Thesis / Doctor of Philosophy (PhD)

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A study was performed to establish the appearance of normal equine laryngeal cartilages using magnetic resonance imaging. Specimens were acquired from clinically normal horses that were euthanized for reasons other than respiratory disease. Three in situ and 5 ex vivo larynges were imaged using a 0.3 Tesla system. Images were obtained in the transverse plane using T1-weighted 3D spin echo, T2-weighted 3D spin echo, T2-weighted gradient echo, short tau inversion recovery (STIR), and proton density spin echo sequences. Five ex vivo larynges were also imaged in the transverse plane using a 1.5 Tesla system, sequences included T1-weighted 3D spin echo, T2-weighted 3D turbo-spin echo, turbo inversion recovery (TIRM), and proton density spin echo sequences. A frozen gross laryngeal specimen was sliced in 5-mm transverse sections for comparison to the MR images. Excellent correlation was found between MR images and the gross transverse sections. Successful imaging was accomplished using both imaging systems; however, the 1.5 Tesla system yielded superior image resolution. The 0.3 Tesla imaging system would accommodate the intact equine head, which was not possible using the 1.5 Tesla MRI system. The internal morphology of the laryngeal cartilages was clearly identified in all imaging sequences obtained. Cartilages were found to differ in signal intensity based on the tissue composition and imaging sequences performed. MRI was determined to be a useful imaging modality for evaluating the cartilage morphology of the equine larynx. Further investigation is required to document pathologic morphology. / Master of Science

Yes / Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention in paediatric patients. Ultrasound is generally the diagnostic imaging modality of choice, followed by CT, where paediatric appendicitis is suspected. However, high operator dependency and diagnostic restrictions related to anatomical and clinical presentation may limit consistency of application. This paper explores whether MRI is a viable alternative to ultrasound as the primary imaging modality. Method: A systematic review of the literature was undertaken. A search of Medline, Cinahl, PubMed Central and Google Scholar was undertaken supplemented by a review of reference lists, author searching and review of NICE evidence base for existing guidelines. Included studies were assessed for bias using the QUADAS-2 quality assessment tool and data were extracted systematically using a purposefully designed electronic data extraction proforma. Results: Seven studies were included in final review. The age range of participants extended from 0 to 19 years. Only one study with a patient age range of 0e14 used sedation. Sensitivity estimates from the included studies ranged from 92% to 100% while specificity ranged from 89% to 100%. A significant variation in the number and type of sequences was noted between the studies. Conclusion: MRI offers high sensitivity and specificity comparable to contrast enhanced CT and greater than ultrasound as reported in the literature. Where accessibility is not a restriction, MRI is a viable alternative to ultrasound in the assessment and diagnosis of paediatric appendicitis. Clinical practice recommendations have been provided to facilitate the translation of evidence into practice.

He Wu-jing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 48-57). / Abstracts in English and Chinese. / Abstract --- p.ii / Chinese Abstract (論文摘要) --- p.iv / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Tables --- p.viii / List of Figures --- p.ix / Chapter Chapter 1 - --- fMRI as a Neuroimaging Method --- p.1 / Chapter Chapter 2 - --- An Review of the Relationship Between Prefrontal Lobes and Memory --- p.6 / Chapter Chapter 3 - --- The Present Study --- p.12 / Chapter Chapter 4 - --- Method --- p.17 / Chapter Chapter 5 - --- Results --- p.25 / Chapter Chapter 6 - --- Discussion --- p.41 / References --- p.48

(1) MRI is shown to be an accurate test for detecting NPC and one which has the potential to be used in screening to (a) screen out normal patients who do not require endoscopie biopsy; and (b) identify small tumours that would be missed on endoscopy. / (2) At diagnosis staging NPC by MRI reveals that oropharyngeal and maxillary sinus invasion are markers of more advanced disease than reflected in current staging system. Tumour involvement of the preclival/prevertebral region, skull base and retropharyngeal nodes are more common than previously recognised by computed tomography, while parapharyngeal tumour invasion is less common. The latter resuits from the superior ability of MRI to differentiate primary tumours with true parapharyngeal invasion from those contained within the nasopharynx which are causing bowing of the wall or lie adjacent to a retropharyngeal node. / (3) Post treatment complications were detected by MRI in over 50% of patients. Neural damage, especially to the temporal lobes and 12th cranial nerves, was the most frequent complication (48%), followed by osteoradionecrosis (20%) involving the mandible, upper cervical spine and skull base, the latter including destruction of the roof of the nasopharynx. Malignant tumours and unusual benign masses (6%) showed radiological features useful in the differential diagnosis from NPC recurrence. Malignant tumours were mainly squamous cell carcinomas or sarcomas showing a predilection for the maxillary region, tongue and external auditory canal. The unusual benign masses were found in the nasopharynx/sphenoid sinus. / (4) Finally functional MRI using DWI and 1H-MRS are feasible in the technically challenging region of the head and neck. Choline ratios and ADC values of NPC are established. The successful demonstration of differences between the biomarkers of NPC and those of lymphoma and squamous cell carcinoma, show that functional MRI is a new tool for the evaluation of NPC, opening up the possibility that these biomarkers can be used for monitoring NPC treatment response in the future. / Magnetic resonance imaging (MRI) provides excellent anatomical detail and functional information about cancer. This thesis explores the role of MRI in the assessment of nasopharyngeal carcinoma (NPC) from detection through to the long term complications of radiotherapy treatment. / Ann D King. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3468. / Thesis (M.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 180-191). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English only. / School code: 1307.

Two-dimensional spatially selective radiofrequency (2DRF) pulse is a type of excitation radiofrequency (RF) pulse in magnetic resonance imaging (MRI) which selects and excites spins in two dimensions simultaneously. Due to its extra selectivity on the second dimension compared with conventional one-dimensional RF pulse, 2DRF pulse could realize reduced field of view (rFOV) imaging. 2DRF-enabled rFOV imaging can accelerate imaging speed, and improve image quality significantly. Advances of 2DRF pulse have been achieved in recent years. However, its wide application in routine clinical practice is hindered by rigid design of 2DRF pulse, the long pulse duration, the inflexibility in excitation pattern, and the user-unfriendliness for non-specialists. The objective of this thesis work is to develop a high-efficient and user-friendly 2DRF pulse to improve its usability and efficiency in routine clinical practice, especially for non-specialists. Finally, the feasibility and applicability of the developed 2DRF pulse was verified in human spine T₁ₚ MR imaging and chemical exchange saturation transfer (CEST) imaging. / A high-low echo planar (EP) 2DRF pulse was first developed to realize rFOV imaging. Developed 2DRF pulse was evaluated in both phantom and human brain. The advantages of being robust to moderate gradient system delay and higher image signal to noise ratio (SNR) of the proposed 2DRF pulse were characterized by the better excitation profiles compared with conventional EP 2DRF pulse sequence. Additionally, the flexibility of the developed 2DRF pulse was verified by the constant image qualities and excitation profiles at different on-line setups. These results demonstrated the feasibility and user-friendliness of the high-low EP 2DRF pulse and revealed its potential application in routine clinical practice. / The high-low EP 2DRF pulse was then incorporated into T₁ₚ sequence to realize rFOV spine T₁ₚ imaging. Quantitative T₁ₚ imaging is time consuming in particular for high spatial resolution images obtained with high spin-lock frequency (FSL) though fast acquisition techniques could be employed. In addition, spine T₁ₚ imaging is vulnerable to the artifact induced by respiration and fat-water chemical shift. Reduced field of view in phase encoding (PE) direction helps to shorten the acquisition time, while preserving the SNR and resolution. The respiration artifact can be eliminated as no spin in chest or abdomen is excited. The 2DRF-enabled rFOV T₁ₚ imaging shortened scan time to the half and minimized respiration artifacts. rFOV CEST imaging was realized by the high-low EP 2DRF pulse. The feasibility of 2DRF pulse enabled rFOV CEST imaging was demonstrated. / 二維空間選擇射頻脈衝（2DRF）是一種磁共振成像中的激發脈衝。它能夠在兩個維度上同時地選擇性激發自旋。和傳統的一維選擇射頻脈衝相比，2DRF 在另一維度上額外的選擇能力使之能夠實現小視域成像。2DRF小視域成像能夠大幅加快成像速度以及提高圖像質量。近年來，2DRF的理論和實驗成果日益豐碩，但2DRF的廣泛臨床應用受到了其相對複雜的設計，較長的激發時間，不夠靈活的激發模式，對組織磁敏感性的過於靈敏以及對於非專業人士的難以操控性等諸多因素的阻礙。這篇碩士論文所述工作的目的是開發一種高效以及易操控的2DRF,以提高它在臨床應用中的實用性和易用性。而後，在人體脊柱T1ₚ磁共振成像和化學轉移飽和交換（CEST）成像技術中，驗證了所提出的2DRF的可行性和適用性。 / 一種高-低回波平面2DRF被首次提出并用於實現小視域成像。這種2DRF在水模和人體腦部成像中得以檢驗。相較於一般的平面回波2DRF，其具有對梯度線圈系統延遲的魯棒性，以及較高的信噪比。這些優勢體現于較好的激發圖樣中。此外，此種2DRF的靈活性在多種設定中取得的穩定的圖像質量和激發圖樣中得到體現。 / 所提出的高-低回波平面2DRF隨後與T1ₚ磁共振成像序列相結合實現了小視域脊柱T1ₚ成像。量化T1ₚ成像比較費時，特別是在使用較高自旋鎖定頻率或者較高的成像分辨率時。此外，脊柱T1ₚ成像容易受到呼吸運動以及水脂化學位移導致的偽影的影像。小視域成像在相位編碼方向上減少了成像範圍，從而在保證圖像信噪比和分辨率的同時減少了圖像採集時間。由於沒有腹部的自選電子被激發，呼吸運動偽影也得以消除。小視域脊柱T1ₚ成像大幅減少成像時間至常規時間的一半以下且最大程度地消除了呼吸運動偽影。通過應用這種2DRF,小視域化學轉移飽和交換轉移成像隨後也得以實現。在研究中，這種成像技術的可行性得到了證明。 / Zhang, Qinwei. / Thesis M.Phil. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 69-79). / Abstracts also in Chinese. / Title from PDF title page (viewed on 11, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Since the advent of functional magnetic resonance imaging (fMRI) and the rise in popularity of its use for resting state functional connectivity mapping (rs-FCM) to non-invasively detect correlated networks of brain activity in human and animal models, many resting state FCM studies have reported differences in these networks under pathologies such as Alzheimer’s or schizophrenia, highlighting the potential for the method’s diagnostic relevance. A common underlying assumption of this analysis, however, is that the blood oxygen level dependent (BOLD) signal of fMRI is a direct measurement of local neural activity. The BOLD signal is in fact a measurement of the local changes in concentration of deoxy-hemoglobin (HbR). Thus, it is imperative that neurovascular coupling—the relationship between neuronal activity and subsequent hemodynamic activity—be better characterized to enable accurate interpretation of resting state fMRI in the context of clinical usage. This dissertation first describes the development and utility of WFOM paradigm for the robust and easily adaptable imaging of simultaneous neuronal and hemodynamic activity in awake mouse models of health or disease in strains with genetically encoded fluorescent calcium reporters. Subsequent exploration of resting state WFOM data collected in Thy1-GCaMP3 and Thy1-GCaMP6f mouse strains is then presented, namely the characterization of spatiotemporal patterns of neuronal and hemodynamic activity and different modulatory depths of neuronal activity via a toolbox of unsupervised blind source separation (e.g. k-means clustering) and supervised (e.g. non-negative least squares, Pearson correlation) analysis tools. The presence of these different modulatory depths of neuronal activity were then confirmed in another Thy1-jRGECO1a mouse strain using the same imaging scheme. Finally, the dissertation documents the application of the WFOM paradigm and select analysis tools to a novel mouse model of diffusely infiltrating glioma, through which neuronal and hemodynamic activity changes during diffusely infiltrating glioma development which impact temporal coherence of the tumor region activity relative to non-tumor regions activity were recorded and analyzed. The paradigm also allowed for recording of numerous spontaneous occurrences of interictal neuronal activity during which neurovascular coupling is modified in the tumor, as well as occurrences of non-convulsive generalized seizure activity (during which neurovascular is non-linear and cortex eventually suffers hypoxia). The detection of spatiotemporal patterns and different modulatory depths of activity in the awake mouse cortex, as well as observation of changes in functional activity in the context of diffusely infiltrating glioma, provide us with new insights into the possible mechanisms underlying variations in resting state connectivity networks found in resting state fMRI studies comparing health and disease states.