Magnetic Resonance Spectroscopy (MRS) was used to study the relationship between brain regional concentrations of metabolites and normal aging in Chinese. Our goal in this study is to create a database of normal aging and hence enhance further understanding on the degenerative process leading to dementia and related neurodegenerative diseases. Thirty cognitively normal healthy volunteers of age 22-82 years were recruited and the bias on gender effect in data sampling was minimized by recruiting 15 females and 15 males. In the first part of the study, 1H MRS was obtained using single-voxel-spectroscopy (SVS). Offline software java-based version of Magnetic Resonance User Interface (jMRUI) was employed for data analysis. Cerebrospinal fluid was normalized using software voxel based morphormetry (VBM). Brain morphometry data was also analyzed. Brain metabolites choline (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were quantified using internal water as reference. It was found that brain metabolite concentrations of Cr, Cho and NAA increase significantly with age. Gender effect on metabolite concentrations were also discovered, being higher in the female group. For brain morphometry, white matter and grey matter volumes and fractions all reveal a siginificant negative correlation with age, whereas CSF volume and fraction show a significant positive correlation with age. Gender effect was found on grey matter, white matter and intracranial volume, being higher in the male group. In the second part of the study, 31P SVS MRS was performed on the same population of volunteers. jMRUI was also employed for data analysis. Metabolic ratios were obtained. Similar to the 1H MRS study, apart from creating a database in studying normal aging, an additional aim of this 31P MRS study is to correlate with 1H MRS and assist in interpreting the corresponding metabolic activity. Brain metabolite concentrations were found to increase significantly with age. The increase of PCr (phosphocreatine)/Ptot (total phosphorus content) in posterior cingulate suggests lower metabolic activity throughout the course of aging. The strong evidence of PDE (phosphodiester) increase with age in left hippocampus proposes the fact that phospholipid membrane breakdown will be enhanced by aging. In conclusion, MRS can act as a non-invasive tool to study aging at molecular level. Metabolite levels are significant means to investigate the metabolic change in the human brain during the process of aging as the variations in metabolite levels are believed to be footprints of biochemical changes. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

abstract / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

As compared with other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) provides distinctive advantages with better contrast and resolution in imaging brain anatomy and function in vivo. As compared with electrophysiological and histological tracing techniques, MRI enables longitudinal investigation with higher efficiency, lower labor cost and less possibility of sampling error. The major objective of this doctoral work is to utilize cellular and molecular MRI to investigate normal brain functions and injuries in vivo. The results successfully demonstrated MRI as an efficient and sensitive tool for providing comprehensive assessment of brain injuries for promoting accurate prognosis and timely intervention, and for studying fundamental questions with regard to cortical adaptations to challenges in the young adulthood. Firstly, diffusion tensor imaging (DTI) and T2-weighted imaging were employed to characterize longitudinal neuronal and axonal changes of pyramidal tract (PY), a critical part of corticospinal tract, following experimental intracerebral hemorrhage (ICH). Combining DTI with T2-weighted imaging results, ipsilateral PY injuries following ICH were diagnosed as four stages. Quantitative analysis revealed transient diffusivity decreases in PY both contralateral and ipsilateral to the primary hemorrhagic site. Evolution of the ipsilateral DTI parameters correlated with histological findings and indicated evolving and complex pathological processes underlying monotonic FA decrease. These results demonstrated multi-parametric DTI as a valuable imaging tool for non-invasive and longitudinal monitoring of secondary PY injuries. Secondly, DTI and manganese-enhanced MRI (MEMRI) were utilized to detect neuronal changes of substantia nigra (SN) following experimental ICH in rodents. DTI revealed early changes in SN both contralateral and ipsilateral to the primary hemorrhagic site. Evolution of the ipsilateral parameters correlated with the histological results. MEMRI provided insights into the cellular phenotype changes at the late stage. DTI can serve as a valuable imaging tool for non-invasive early detection and longitudinal monitoring of secondary SN injuries, while MEMRI could complementally provide information regarding the late stage inflammation process. Multi-parametric MRI could facilitate clinical and preclinical investigations of SN injuries for exploring disease mechanisms and developing new therapeutic strategies. Thirdly, MEMRI was performed to characterize the interhemispheric interactions in normal and monocularly deprived rodent visual brain. Characteristic transcallosal manganese labeling was observed in the normal group in a manner consistent with previous histological findings. Significant decrease of such labeling was observed in rats with left or right eyelid suturing, or with left eye enucleation, but not in rats with right eye enucleation. These results demonstrated MEMRI as an efficient tool for investigating interhemispheric interactions both anatomically and functionally. These results also indicated that the adult brain recruits different mechanisms for its adaptations to eyelid suturing and enucleation, thus shedding light on our understanding of the transcallosal interhemispheric excitation and inhibition. Lastly, new paradigms other than pressure injection for intracortical manganese administration in MEMRI were introduced to minimize the neuro-toxicity of manganese and maximize the sensitivity of MEMRI for studying cortical functional changes. Transmeningeal diffusion, osmotic pump-based infusion, and intranasal instillation were demonstrated to be successful in tracing interhemispheric connections and detecting stress-related cortical and subcortical changes. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Functional magnetic resonance imaging (fMRI) is a noninvasive technique that can measure blood oxygenation level dependent (BOLD) signal changes in a large field of view with high spatial resolution. The objective of this dissertation is to explore and integrate novel and noninvasive fMRI methods at 7 Tesla to investigate the auditory and visual functions. First, different fMRI methods and stimulation paradigms were employed to explore some basic auditory functions such as sound pressure level (SPL) dependence in different brain structures, and periodotopy and tonotopy in the inferior colliculus (IC). BOLD signal changes increased significantly with SPL and the dependence was monotonic in the IC and lateral lemniscus (LL). The external cortex of IC (ECIC) had higher BOLD signal change than the central nucleus of IC and LL at high SPLs. This study indicates that sparse temporal sampling that is used to reduce the adverse effects of scanner noise may not be a prerequisite in auditory fMRI studies of the IC. Periodotopy and tonotopy in the IC was investigated using continuous imaging with passband balanced steady state free precession (bSSFP) sequence instead of sparse temporal sampling and echo planner imaging (EPI). The spatial gradients of best amplitude modulation frequency (referred to as periodotopy) and characteristic frequency (referred to as tonotopy) varied across the IC, but were approximately perpendicular at different locations. These findings enhance our understanding of how auditory information is preserved in the midbrain. Second, higher order function of behaviorally relevant sounds response selectivity in subcortical structures was investigated. The IC was found to exhibit a stronger response to forward vocalization than to the temporally inverted one. Moreover, blocking cholinergic projections to the IC by atropine injection was observed to significantly reduce the IC response selectivity to the 22 kHz vocalizations. These findings demonstrate the IC response selectivity to vocalizations and suggest that the cholinergic projection contributes to IC responses selectivity to the 22 kHz vocalization. This study provides further understanding about the higher order auditory processing and may have implications for the neural mechanisms underlying human speech perception Third, BOLD fMRI was applied to measure the brain response to stationary and apparent motion visual stimulation. The response of superior colliculus (SC) was weaker under dim light and saturates at higher intensities. Further, the BOLD signal changes and number of activated voxels were both significantly lower during 164 ˚/s apparent motion stimulation compared to stimuli at slower speeds. The results suggest that the SC was more sensitive to slow moving visual stimuli. This is the first fMRI study to investigate motion responsiveness and stimulus speed dependence in the rat SC. Results from these studies complement current knowledge and demonstrate the sophisticated role of subcortical structures such as IC and SC, which may have strong clinical significance to the field of auditory and visual research. Findings from the animal studies should open up new avenues of research and lay the ground work for future human studies. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

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published_or_final_version / abstract / toc / Medicine / Doctoral / Doctor of Philosophy

No description available.

No description available.

The basic theories of Nuclear Quadrupole Resonance are outlined, together with some basic NMR theory and its application to double resonance techniques. An improved design of spectrometer using double resonance is presented, including a description of a new flow cryostat which can operate down to 4.2°K with low (250 cc/hour) consumption of liquid He. The whole apparatus may be used to detect NQR signals in solids over the frequency range 100 kHz-5 MHz. The theory of double resonance with spin mixing by continuous coupling (D R CC) is developed and illustrated by experiments performed on HCOOD, HDO and several nitrogen-containing compounds, including Imidazole. Further experiments were then carried out on samples dilute in deuterium, including the detection of NQR in formic acid (HCOOH) due to naturally abundant deuterium. Other experiments on proton-deuteron interactions in amide groups and in water molecules are also described and compared with results previously published on fully-deuterated amides and D₂0 as a water of crystallisation in L-serine hydrate. The NQR spectrum of Lanthanum Nicotinate Dihydrate is obtained using F.M. techniques and related to its structure. The theory of Zeeman NQR in spin 3/2 nuclei is developed with reference to the double resonance technique, and the measured quadrupole coupling constants of ²³Na and ²D in NaOH and some of its hydrates are discussed. Finally, some standard theories concerning proton relaxation times in solids at low temperatures (4°K-300°K) are outlined and related to some, measured relaxation times, illustrating their significance to the double resonance technique. The concluding chapter outlines a speculative proposal for a new spectrometer design.

NMR spectroscopy is not only for protein structure determination, but also for drug screening and studies of dynamics and interactions. In both cases, one of the main bottleneck steps is backbone assignment. When a homologous structure is available, it can accelerate assignment. Such structure-based methods are the focus of this thesis. This thesis aims for fast and robust methods for NMR assignment problems; in particular, structure-based backbone assignment and chemical shift mapping. For speed, we identified situations where the number of 15N-labeled experiments for structure-based assignment can be reduced; in particular, when a homologous assignment or chemical shift mapping information is available. For robustness, we modeled and directly addressed the errors. Binary integer linear programming, a well-studied method in operations research, was used to model the problems and provide practically efficient solutions with optimality guarantees. Our approach improved on the most robust method for structure-based backbone assignment on 15N-labeled data by improving the accuracy by 10% on average on 9 proteins, and then by handling typing errors, which had previously been ignored. We show that such errors can have a large impact on the accuracy; decreasing the accuracy from 95% or greater to between 40% and 75%. On automatically picked peaks, which is much noisier than manually picked peaks, we achieved an accuracy of 97% on ubiquitin. In chemical shift mapping, the peak tracking is often done manually because the problem is inherently visual. We developed a computer vision approach for tracking the peak movements with average accuracy of over 95% on three proteins with less than 1.5 residues predicted per peak. One of the proteins tested is larger than any tested by existing automated methods, and it has more titration peak lists. We then combined peak tracking with backbone assignment to take into account contact information, which resulted in an average accuracy of 94% on one-to-one assignments for these three proteins. Finally, we applied peak tracking and backbone assignment to protein-ligand docking to illustrate the potential for fast 3D complex determination.