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• Human MR Imaging Research
• BRaIN Imaging Center

Currently our focus is the development of high-speed spectroscopic MR imaging and real-time functional MR imaging for applications in Cancer Research, Neurology and Psychiatry. Here, a few project

• High-Speed Metabolic Imaging in Human Brain
• High-Speed 3D MR Spectroscopic Imaging of Choline in Breast Cancer
• Diffusion Tensor Spectroscopic Imaging

• Real Time Functional MRI
• Pattern Classification in fMRI
• Echo-Volumar Imaging
• Applications of Real-Time fMRI with Neurofeedback

Proton magnetic resonance spectroscopic mapping (1H-MRSI) of brain metabolites can identify biomarkers relevant to psychiatric and neurological disease. There is currently increasing interest in extending 1H-MRSI techniques and processing capabilities to map J-coupled brain metabolite resonances. Glutamate (Glu) and glutamine (Gln) mapping are of particular interest because these metabolites are key components of energy metabolism and nitrogen homeostasis pathways and are also involved in excitatory synaptic neurotransmission. In vivo mapping of glutamate in clinically feasible acquisition times may have important diagnostic applications in psychiatric disorders and studies of aging. However, technical limitations, poor SNR, and data interpretation and analysis complications have prevented widespread use of MRSI in the clinical setting. Some of the most serious limitations of MRSI in the clinical setting are its intrinsically low SNR, long encoding times, limited volume coverage, limited spectral specificity and lack of absolute spectral quantification.

Proton-echo-planar-spectroscopic-imaging (PEPSI) developed in our laboratory has been successfully applied in a number of clinical applications, including panic disorder, autism spectrum disorder, and bipolar disorder. Our recent results using short echo time (TE) PEPSI in human brain demonstrate linear increase in sensitivity between 1.5 and 7 Tesla, and feasibility of 2-dimensional spatial mapping of J-coupled resonances at 3 and 4 T in less than 10 minutes. Clinical studies using this technology are now in progress at several research centers in the United States and Europe.

The development of this technology is an effort to increase clinical utility, reduce cost and establish high-speed MRSI as a clinical tool that can map a wide range of metabolites in human brain and that is complementary to other metabolic brain mapping techniques, such as PET and SPECT. This technological development is applicable to neuroscience, psychiatric and cancer research of normal and diseased brain function, to pre-treatment diagnosis and to monitoring of treatment response using disease-specific metabolic biomarkers.

Magnetic resonance imaging (MRI) is playing an increasingly important role in clinical diagnostics of breast cancer, including screening for breast cancers in high risk women. However, overall specificity has been low, resulting in a considerable number of benign biopsies. Recent studies reported that adding quantitative MR spectroscopy (MRS) results (mostly focusing on total choline) to a dynamic contrast enhanced (DCE) MRI exam produced improvements in the sensitivity, specificity, and accuracy for all readers, and improved the inter observer agreement between the readers. A second promising application of breast MRS involves predicting response to treatment. However, the majority of breast MRS studies to date have used single-voxel spectroscopy (SVS) to localize the spectrum to a single volume centered on the lesion of interest, which does not allow characterization of lesion heterogeneity.

Our research aims at developing high-speed proton MR Spectroscopic Imaging (MRSI) methodology based on Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) to map total Choline to characterize lesion heterogeneity and improve the specificity of a Breast MR exam for disease staging and for treatment monitoring. Accurate early identification of treatment failure or success could save significant time and resources, and minimize patient risk and side effects in evaluation of any new therapy.

Diffusion tensor imaging (DTI) characterization of white matter microstructure abnormalities in autism spectrum disorder (ASD) generally demonstrate decreased water diffusion anisotropy in frontal cortex and corpus callosum, consistent with frontal disconnectivity theories of autism. However, DTI findings in ASD show considerable heterogeneity and little is known about differential involvement of the intracellular and extracellular compartments or mechanisms underlying changes in water diffusion that limit the extent to which DTI can be used to characterize developmental processes in ASD. Diffusion tensor 1H MRSI (DTSI) can provide unique information on intracellular properties, such as viscosity, cell swelling, restriction in subcellular structures and cytoplasmic streaming, that may help to characterize possible inflammatory processes in autism. All human studies so far have used single voxel localization method (e.g. Posse et al 1993a, Ellegood et al 2005 and 2006, Upadhyay et al 2007) due to overwhelming motion sensitivity of conventional MRSI techniques (Posse et al. 1993b), which do not allow mapping of metabolite diffusion across extended brain areas hypothesized to be involved in autism.

The objective of this project is to develop single-shot diffusion sensitive MRSI to dramatically reduce motion sensitivity, and to show feasibility of volumetric mapping of metabolite diffusion in healthy adults and children with ASD using a clinical 3 Tesla whole body scanner.

Functional MRI based on blood-oxygenation-level-dependent (BOLD) contrast is a technology that has found widespread application in cognitive neuroscience. At the same time, the sensitivity of data acquisition methodology has evolved to the point that brain activation can be detected in single trials and there is increasing interest in mapping brain activity in individual subjects for the purpose of understanding inter-individual differences in cognitive processing. Clinical applications for presurgical mapping and interactive brain-imaging-guided exams of patients suffering from psychiatric and neurological disorders are foreseeable.

Real-time fMRI is a variant of fMRI that enables monitoring of changes in brain activation during the ongoing scan. It is characterized by steady-state image reconstruction, preprocessing and statistical analysis in a time frame that is short with respect to the time to acquire a volume fMRI data set, and with a time delay from data acquisition that is shorter than the hemodynamic response delay, which is on the order of several seconds. Real-time fMRI offers new intriguing opportunities for monitoring brain processes related to thoughts and emotions. Using novel highly sensitive real-time data acquisition methods based on multi-echo Echo-Planar-Imaging (EPI) and real-time sliding-window correlation analysis, we have shown that it is possible to monitor dynamic changes in brain activation during brief motor, visual, auditory and cognitive tasks with an effective temporal resolution of just a few seconds. Recent real-time fMRI studies have demonstrated the feasibility of modulating brain activity in localized areas for the purpose of accelerated learning, to develop novel brain-computer interfaces for communication and for controlling pain perception in patients with chronic pain.

Our technology development is aimed at innovative individualized designs of fMRI experiments, which include, but are not limited to, (a) interactive brain-imaging-guided interview of patients suffering from psychiatric and neurological disorders that are refractory to conventional diagnosis and treatment, and (b) individualized training of mental abilities and control of brain activation patterns through the use of experimental feedback. The first approach is of importance in situations where the subject is either unable (e.g., stroke victims, babies and young children, many schizophrenic patients, many patients with major depression) or unwilling (e.g., in situations where deception is used) to accurately report his/her mental experience. The second approach is of interest for developing individually tailored training strategies for operators of complex machine-human interfaces (e.g., automobile driver, pilots) and for developing individually tailored mental learning strategies. Such capabilities would constitute a breakthrough in cognitive neuroscience, because they open the elusive world of human thought processes to rigorous neural systems level analysis.

Click to read the MIT Technology Review (11/06/2006) article by Emily Singer: Watching a Single Thought Form in the Brain— New techniques to capture single thought processes open up new possibilities for neuro-imaging.

Pattern classification is a growing area of research in fMRI that aims at interpreting activation patterns in terms of underlying cognitive processes. Recent studies have demonstrated a high degree of pattern specificity for discrete neural processes and it is expected that pattern classification will play a major role in understanding cortical organization in individual subjects. Specifically, automatic interpretation and classification of neuroimaging data may hold important keys for understanding the human mind, which has raised interests due to the potential clinical applications. Information embedded in the spatial shape and extent of activation patterns, and differences in voxel-to-voxel time course, are not easily quantified with conventional analysis tools, such as statistical parametric mapping (SPM). Pattern classification in functional MRI (fMRI) is a novel approach, which promises to characterize subtle differences in activation patterns between different tasks. There is growing evidence that exquisite pattern specificity exists in visual cortex and other brain areas, such as motor cortex, auditory cortex and parietal cortex. However, automatic and reliable classification of patterns is challenging due to the high dimensionality of fMRI data, the small number of available data sets, inter-individual differences in activation patterns, and dependence on the image acquisition methodology. We recently introduced spatially distributed classifier for boosting to further reduce the dimensionality problem.[18 ]

Our technology development is aimed at improving automated pattern classification to facilitate clinical applications of fMRI, such as fMRI-guided mental training, identification of disease markers (e.g. psychiatric disorders, epilepsy, migraine), and prediction of treatment response and relapse.

Echo volumar imaging (EVI) has the potential to become an alternative to echo planar imaging (EPI) as the accelerating development of parallel imaging and large-scale array coils transforms clinical imaging [Rabrait et al 2008, van der Zwaag et al 2006, Witzel et al 2008]. The high temporal resolution reduces intrascan motion effects, it enables assessment of regional differences in hemodynamic response function and it reduces aliasing of physiological noise. However, geometrical distortion and blurring due to field inhomogeneity and relaxation are significant challenges. Practical applications are hampered by time-consuming image reconstruction and real-time fMRI with EVI has yet to be demonstrated.

In this study we develop multiple-slab EVI for high field applications to reduce geometrical distortion and blurring. We demonstrate real-time fMRI using custom designed high-performance data transfer and analysis tools. We compare BOLD sensitivity with conventional EPI, characterize the time course of the hemodynamic response function in single trial paradigms and investigate resting state networks.

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Applications of Real-Time fMRI with Neurofeedback

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