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

Magnetic Resonance Imaging (MRI) is a non-ionizing imaging modality that can provide images with excellent soft tissue contrast at high resolution. In particular, molecular and cellular MRI is a powerful imaging method that could provide a non-invasive way for assessing specific biological processes in vivo in living organisms. The ability to monitor and track biological structures and processes down to molecular and cellular level and the possibility to probe the development, survival, migration, and differentiation of cells in vivo, has opened up new ways for scientists to investigate the fundamental mechanisms of health and diseases. In this dissertation, novel applications of conventional MR contrast agents to study specific biological structures and processes are demonstrated. First, the potential of manganese enhanced MRI (MEMRI) for in vivo tract tracing and assessment of neuroarchitecture was investigated. Manganese was intracortically infused into the visual cortex along the border of the primary and secondary visual cortex and then imaged 8 and 24 hours later. A dynamic migratory path of manganese from the infusion site through the corpus callosum to the contralateral hemisphere was observed. Also, layer specific enhancement on the contralateral cortex and the connection of the visual cortex with other brain structures were shown and the results were consistent with established anatomical data. Secondly, MEMRI was performed to probe in vivo neuronal changes in the rodent brain following 72-hour rapid eye movement sleep deprivation. Significant reduction in manganese uptake was observed in the cortical and hippocampal region in the sleep deprived animals when compared to the normal group. In particular, the dentate gyrus substructure in the hippocampus exhibited the least uptake. This indicated the functional vulnerability of the hippocampus and the cortex to sleep deprivation. Lastly, in vivo tracking of endogenous neural stem and progenitor cell migration during neurogenesis in neonatal rat brain was performed by micron sized iron oxide particles (MPIO) labeling. Susceptibility weighted imaging was used for image processing to highlight the susceptibility contrast induced by the iron oxide particles. MPIO-labeled cells induced contrast was clearly enhanced in the susceptibility weighted images, particularly at day 3 after MPIO injection in which the MPIO-labeled NPCs became more dispersed in the olfactory bulb. The ventral migratory pathway of endogenous neural stem and progenitor cells, which could not be easily observed in conventional T2*W imaging, couldalsobe detected. Overall, various biological systems and processes have been successfully interrogated using MR contrast agents. Through these studies, the versatility and power of molecular and cellular MRI have been demonstrated. Looking ahead, the rapid development and combination of different molecular and cellular imaging techniques would certainly revolutionize the way we study health and diseases. In the end, this could foster our understanding of basic life sciences and hence improve the quality of healthcare. / published_or_final_version / Electrical and Electronic Engineering / 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

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

published_or_final_version / abstract / toc / Linguistics / Master / Master of Philosophy

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (M.Eng.). / Written for the Dept. of Biomedical Engineering. Title from title page of PDF (viewed 2008/04/12). Includes bibliographical references.

Thesis (M.S. in Biomedical Engineering)--Vanderbilt University, Dec. 2006. / Title from title screen. Includes bibliographical references.

Simultaneous EEG-fMRI is a multi-modal neuroimaging technique where hemodynamic activity across the brain is measured at millimeter spatial resolution using functional magnetic resonance imaging (fMRI) while electrical activity at the scalp is measured at millisecond resolution using electroencephalography (EEG). EEG-fMRI is significantly more challenging to collect than either modality on its own, due to electromagnetic coupling and interference between the modalities. The rationale for collecting the two modalities together is that, given the complementary spatial and temporal resolutions of the individual modalities, EEG-fMRI has the potential as a non-invasive neuroimaging technique for recovering the latent source space of neural activity. Inferring this latent source space and fusing these modalities has been a main challenge for realizing the potential of simultaneous EEG-fMRI for human neuroscience. In this thesis we develop a principled and interpretable approach to address this inference problem. We build on the knowledge of the generative processes underlying image/signal formation of each of the modalities, traditionally viewed via linear mappings, and recast this into a framework which we refer to as “neural transcoding”. The idea of neural transcoding is to generate a signal of one neuroimaging modality from another by first decoding it into a latent source space and then encoding it into the other measurement space. We implement this transcoding via deep architectures based on convolutional neural networks. We first develop a basic transcoding architecture and test it on simulated EEG-fMRI data. Evaluation on simulated data enables us to assess the model’s ability to recover a latent source space given known ground truth. We then extend this architecture and add a cycle consistency loss to create a cycle-CNN transcoder and show that it outperforms, in terms of the fidelity of recovered source space, both the basic transcoder as well as traditional source estimation techniques, even when we provide those techniques detailed information about the image generation process. We then assess the performance of the cycle-CNN transcoder on real simultaneous EEG-fMRI datasets including an auditory oddball dataset and a three-choice visual categorization dataset. Without any prior knowledge of either the hemodynamic response function or leadfield matrix, the transcoder is able to exploit the temporal and spatial relationships between the modalities and latent source spaces to learn these mappings. We show, for real EEG-fMRI data, the modalities can be transcoded from one to another, and that the transcoded results for unseen test data, have substantial correlation with the ground truth. In addition, we analyze the source space of the transcoders and observe latent neural dynamics that could not be observed with either modality alone--e.g., millimeter by millisecond dynamics of cortical regions representing motor activation and somatosensory feedback for finger movement. Collectively, this thesis demonstrates how one can incorporate a principled understanding of the generative process underlying biomedical image/signal formation in a deep learning framework to build models that are interpretable and symmetrically combine both modalities. It also potentially enables a new type of low-cost computational neuroimaging -- i.e., generating an ``expensive" fMRI BOLD image from ``low cost" EEG data.