The theme of the proposed project is to develop a functional template or atlas of the normal pediatric brain, based on quantitative cerebral blood flow (CBF) measurements using arterial spin labeling (ASL) perfusion MRI. Parenchymal perfusion is an important physiologic parameter in the evaluation and management of brain disorders as well as a surrogate index of neural activity. Such information, especially normative perfusion data, has been sparse in the pediatric population due to the safety concerns and technical difficulties associated with existing methods to measure perfusion that rely on radioisotopes and contrast agents. ASL perfusion MRI offers a great potential for pediatric perfusion imaging, because it is totally noninvasive and provides improved image quality due to increased blood flow and water content of the child brain. Building on the ongoing efforts at our institutes involving technical developments of pediatric perfusion imaging, structural normalizations of the child brain and cognitive neuroscience studies on neurogenetic diseases, we propose to specifically develop the methodologies and pilot them in the construction of a perfusion based functional template of the pediatric brain.
Four specific aims are proposed in this project.
In Aim 1, we plan to improve the accuracy of the co-registration of structural and functional MR images by reducing susceptibility effects and geometric distortions in ASL perfusion MRI;
In Aim 2, we will optimize the methods for the construction of a functional template of normal CBF in children aged 7 to 18 years, following the normalization transformation determined from high resolution anatomical brain images;
In Aim 3, we will validate the developed template via quantitative assessment of perfusion anomalies in children afflicted with chromosome 22q11.2 deletion syndrome, and compare functional defects with structural abnormalities. Last in Aim 4, we will test the feasibility of developing a pediatric database of brain perfusion, through collaboration with multiple pediatric neuroimaging sites. The proposed project is expected to shed light on the evolution of normal brain function with age as well as to provide a reference system for future clinical and cognitive neuroscience studies on childhood brain disorders. It may also contribute to developmental cognitive neuroscience and provide valuable information on the 22q11.2 deletion syndrome - a highly prevalent yet ill-understood genetic disease. Given the proposed database that will collect images from collaborating sites, the successful completion of this pilot project will lead to a large-scale (multi-center) project to study structural and functional brain development under normal or pathological conditions.
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