The goal of stroke treatment is to limit infarct size, improve outcome and prevent recurrence. A consensus is emerging from studies of adult stroke that multimodal MRI may play an important role in determining the volume of tissue that is at risk. Particularly, patients with regions of hypoperfusion larger than the volume of tissue with low diffusion are more likely to experience substantial enlargement of the infarct volume over time, a selection criteria for thrombolytic therapy in acute stroke. The mechanisms and outcome of pediatric stroke, however, are very poorly understood with no accepted protocol for patient treatment and management. The difficulty resides in the diverse etiology and clinical manifestations of pediatric stroke as well as the lack of suitable evaluation technology. Existing cerebral blood flow (CBF) measurements in adults cannot be easily applied on children due to safety concerns related to the use of radioisotopes and the logistical difficulties in rapidly injecting contrast agents in pediatric patients. Arterial spin labeling (ASL) perfusion MRI is a promising technology to directly measure CBF by utilizing magnetically labeled arterial blood water as endogenous tracer. This technique is ideally suited for pediatric imaging because it is totally noninvasive and provides improved image quality due to increased blood flow and water content of the pediatric brain. During recent years, we have developed and validated a suite of ASL methods to assess the hemodynamic status in cerebrovascular disease based on measurements of CBF and arterial transit time. Capitalizing on the latest advancement at high magnetic field, the image quality of these ASL methods has been greatly improved and approaching regular structural MRI scans. Building on the extensive experience in the development and application of ASL perfusion MRI at the University of Pennsylvania and the rich clinical resources at the Children's Hospital of Philadelphia, this proposed project will use the latest high field ASL methods to assess the hemodynamic status in pediatric stroke patients, aiming to probe the brain tissue at risk and predict the potential neurological outcome. In three specific aims, we will measure regional CBF, arterial transit time using ASL techniques along with diffusion imaging in pediatric stroke patients. We will then compare the deficit volumes detected in perfusion, diffusion and transit time modalities with the eventual infarct volume probed by follow up T2 lesion. The predicted outcome is that the volume of perfusion deficits detected in ASL images will be best correlated with T2 lesion volume. The obtained results are expected to enrich the understanding of the mechanism and development of pediatric stroke, as well as contribute to a standard for patient evaluation and treatment. The optimized pediatric ASL technique has potentially wide applicability in childhood brain disorders including sickle cell disease, neoplasm, peri ventricular leukomalacia etc. This project is therefore expected to advance the general application of ASL in the diagnosis, prognosis and management of pediatric brain disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD049893-01
Application #
6911187
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Nicholson, Carol E
Project Start
2005-09-15
Project End
2007-08-31
Budget Start
2005-09-15
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$165,456
Indirect Cost
Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Chen, Juan; Licht, Daniel J; Smith, Sabrina E et al. (2009) Arterial spin labeling perfusion MRI in pediatric arterial ischemic stroke: initial experiences. J Magn Reson Imaging 29:282-90
Rao, Hengyi; Wang, Jiongjiong; Giannetta, Joan et al. (2007) Altered resting cerebral blood flow in adolescents with in utero cocaine exposure revealed by perfusion functional MRI. Pediatrics 120:e1245-54
Wu, Wen-Chau; Fernandez-Seara, Maria; Detre, John A et al. (2007) A theoretical and experimental investigation of the tagging efficiency of pseudocontinuous arterial spin labeling. Magn Reson Med 58:1020-7
Wang, Jiongjiong; Licht, Daniel J; Silvestre, David W et al. (2006) Why perfusion in neonates with congenital heart defects is negative--technical issues related to pulsed arterial spin labeling. Magn Reson Imaging 24:249-54
Wang, Jiongjiong; Licht, Daniel J (2006) Pediatric perfusion MR imaging using arterial spin labeling. Neuroimaging Clin N Am 16:149-67, ix