The theme of the proposed project is to develop a functional template or atlas of the developing brain based on quantitative cerebral blood flow (CBF) measurements using arterial spin labeling (ASL) perfusion magnetic resonance imaging (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 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 is ideally suited for pediatric perfusion imaging, because it is totally noninvasive and provides high image quality due to unique physiologic properties of a child brain. The capability for absolute CBF quantification is another desirable feature of ASL for longitudinal studies to follow neurodevelopmental changes. Through a pilot Human Brain Project funded by NIMH (R21- MH072576, PI: Wang), we have established the feasibility of pediatric perfusion MRI using ASL, and demonstrated the developmental trajectory of CBF in healthy children as well as perfusion aberrations in pre-clinical and clinical pediatric populations. The proposed R01 project represents a continued and systematic effort to address the functional development of a child brain utilizing ASL perfusion MRI. We will first establish the test-retest repeatability and determine the optimal ASL technique along with imaging parameters for constructing the pediatric perfusion template. The accuracy of ASL CBF measurement in children will be validated using global flow rate to the brain determined by phase contrast MRI technique. In the following 4 years, we will develop the normative developmental template of brain perfusion in healthy children aged 7-16 based on ASL perfusion measurements at baseline. In the last aim, we will characterize the quantitative CBF changes in response to a well-characterized cognitive paradigm - working memory tasks - using a concurrent ASL and BOLD (blood-oxygen-level- dependent) fMRI paradigm. Once developed, the pediatric perfusion template will not only shed light on the evolution of brain function with age, but will also provide a valuable resource and reference system for future developmental neuroscience studies as well as clinical studies on childhood brain disorders.

Public Health Relevance

The proposed project will develop a functional template or atlas of the cerebral blood flow (perfusion) in healthy children aged 7-16 years. A noninvasive magnetic resonance imaging technique termed arterial spin labeling will be used to measure perfusion of a child brain with high precision and spatial resolution. The developed pediatric perfusion template will not only shed light on the evolution of brain function with age, but will also provide a valuable resource and reference system for future clinical and cognitive neuroscience studies on childhood brain disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080892-05
Application #
8443415
Study Section
Special Emphasis Panel (ZRG1-NT-B (01))
Program Officer
Freund, Michelle
Project Start
2009-04-15
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$514,522
Indirect Cost
$180,417
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Jann, Kay; Hernandez, Leanna M; Beck-Pancer, Devora et al. (2015) Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder. Brain Behav 5:e00358

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