Sickle cell disease (SCD) is the most common hemoglobin mutation in the US, affecting 60,000 people. SCD is often associated with focal brain abnormalities that worsen as the disease progresses, and conventional MRI (cMRI) can demonstrate focal damage even in infants. At least 1 in 4 SCD patients show cMRI evidence of focal abnormality by age 20. However, we hypothesize that diffuse brain abnormality is actually more common than focal damage, and that it usually precedes focal damage. Because diffuse abnormality cannot be well-visualized by cMRI methods, the prevalence of diffuse abnormality is not known. Our goal is to determine whether new quantitative MRI (qMRI) methods are more sensitive than cMRI methods to diffuse brain damage in SCD patients, and to ascertain whether diffuse brain abnormality correlates with the clinical course of disease. We will use qMRI methods developed in our lab, in a prospective, longitudinal, clinical study of young SCD patients. We will enroll 50 patients and 50 sibling controls, and follow all enrolled subjects prospectively for 5 years. We will use T1 mapping and quantitative MR angiography (qMRA), to characterize the prevalence and to evaluate the significance of diffuse brain abnormality in pediatric SCD patients. Data from cMRI, qMRI and qMRA will be correlated with clinical and psychometric data, to determine which MR imaging data are predictive of clinical severity or development of cognitive deficits. To be specific, we will: characterize the relationship between diffuse T1 reduction and focal brain abnormality detected by cMRI; determine if diffuse T1 reduction is associated with subtle loss of gray or white matter volume measured by cMRI image segmentation; ascertain if diffuse T1 reduction is correlated with psychometric deficit; and establish whether diffuse T1 reduction is associated with vasculopathy, including ectasia or stenosis of the cranial arteries. Because infarctive stroke risk in young SCD patients is 6-fold higher than in healthy adults, SCD patients may provide a clinical model for the most common type of stroke in elderly adults. We will establish whether these novel qMRI methods provide a sensitive and clinically-relevant indicator of diffuse brain injury. Our long- range goal is to determine the mechanisms causing cognitive loss in SCD patients, in an effort to determine a therapeutic strategy to minimize such damage in these patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060022-03
Application #
6389873
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Evans, Gregory
Project Start
1999-07-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
3
Fiscal Year
2001
Total Cost
$338,463
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Steen, R Grant; Fineberg-Buchner, Charlotte; Hankins, Gisele et al. (2005) Cognitive deficits in children with sickle cell disease. J Child Neurol 20:102-7
Steen, R Grant; Ogg, Robert J (2005) Abnormally high levels of brain N-acetylaspartate in children with sickle cell disease. AJNR Am J Neuroradiol 26:463-8
Steen, R Grant; Emudianughe, Temitope; Hunte, Michael et al. (2005) Brain volume in pediatric patients with sickle cell disease: evidence of volumetric growth delay? AJNR Am J Neuroradiol 26:455-62
Haselgrove, John; Hunte, Michael; Hurh, Peter et al. (2004) Direct comparison of two methods to measure T1: in vitro and in vivo values by echo-planar imaging and by segmented k-space imaging. Magn Reson Imaging 22:291-8
Steen, R Grant; Hunte, Michael; Traipe, Elfreides et al. (2004) Brain T1 in young children with sickle cell disease: evidence of early abnormalities in brain development. Magn Reson Imaging 22:299-306
Steen, R Grant; Emudianughe, Temitope; Hankins, Gisele M et al. (2003) Brain imaging findings in pediatric patients with sickle cell disease. Radiology 228:216-25
Steen, R Grant; Hankins, Gisele M; Xiong, Xiaoping et al. (2003) Prospective brain imaging evaluation of children with sickle cell trait: initial observations. Radiology 228:208-15
Steen, R Grant; Xiong, Xiaoping; Langston, James W et al. (2003) Brain injury in children with sickle cell disease: prevalence and etiology. Ann Neurol 54:564-72
Steen, R Grant; Miles, Mark A; Helton, Kathleen J et al. (2003) Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit. AJNR Am J Neuroradiol 24:382-9
Steen, R Grant; Schroeder, Jason (2003) Age-related changes in the pediatric brain: proton T1 in healthy children and in children with sickle cell disease. Magn Reson Imaging 21:9-15

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