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Brain T1 in young children with sickle cell disease: evidence of early abnormalities in brain development
R Grant Steen1, Michael Hunte, Elfreides Traipe
1Department of Diagnostic Imaging, St. Jude Children's Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA. Grant_Steen@med.unc.edu
Insights
Brain T(1) measurements reveal abnormal development in children with sickle cell disease (SCD). Infant patients show higher T(1) values, which normalize by age 4, indicating an altered early developmental trajectory.
Area of Science:
- Neuroscience
- Pediatrics
- Medical Imaging
Background:
- Tissue spin lattice relaxation time (T(1)) is a biomarker for brain development in healthy children.
- Sickle cell disease (SCD) can impact neurological development, but its effects on early brain maturation are not well understood.
Purpose of the Study:
- To investigate brain T(1) in young children with SCD for the first time.
- To compare brain T(1) in SCD patients with healthy controls to identify developmental differences.
Main Methods:
- Measured T(1) in 10 brain tissue samples using established techniques.
- Compared 46 SCD patients (under 4 years) to 267 controls (including 55 healthy children).
- Developed a model to establish age-related T(1) norms in controls.
Main Results:
- Infant SCD patients (<2 years) exhibited significantly higher T(1) values in most white and gray matter tissues compared to controls.
- Caudate T(1) values were significantly higher in SCD patients (15.0% above normal range, p=0.0003).
- T(1) values normalized, then decreased below normal by age 4 in SCD patients.
Conclusions:
- Children with SCD exhibit an abnormal brain developmental trajectory starting in infancy.
- Early brain T(1) alterations suggest potential neurological complications associated with SCD in young children.
- The rapid normalization of T(1) by age 4 warrants further investigation into the underlying mechanisms.
Abstract:
Measurement of tissue spin lattice relaxation time (T(1)) has been used to characterize brain development in healthy children. Here we report the first study of brain T(1) in young children with sickle cell disease (SCD). The T(1) in 10 tissue samples was measured by established techniques; 46 SCD patients under the age of 4 years were compared to 267 controls, including 55 well children under the age of 4 years. A model was developed to predict the relationship between age and brain T(1) in controls, then we compared patient T(1) to healthy normal T(1). Most white matter and gray matter tissues in infant patients (<2 years old), had T(1) values significantly higher than normal. For example, 15.0% of patient caudate T(1) values were above the upper bound of the 95% confidence interval for controls, but only 2.5% of normal values are expected to be this high (p = 0.0003). Among infant patients, brain T(1) was significantly higher than normal in every tissue (p < 0.01) except cortical gray matter. However, patient T(1) values declined rapidly to values lower than normal by about age 4. Our findings imply that patients follow an abnormal developmental trajectory beginning early in infancy.
