Diffusion tensor imaging in children and adolescents: Reproducibility, hemispheric, and age-related differences
Introduction
Diffusion tensor imaging (DTI) (Basser et al., 1994a, Basser et al., 1994b) provides a unique tool to non-invasively visualize and quantitatively characterize brain white matter pathways both in healthy brains (Wakana et al., 2004) and under pathological conditions. For example, prior studies have demonstrated the ability of DTI to identify white and gray matter abnormalities in schizophrenia (Sun et al., 2003), epilepsy (Briellmann et al., 2003) and multiple sclerosis (Cassol et al., 2004), reflecting microstructural changes underlying the disease processes.
Since DTI is becoming part of many standard clinical MRI protocols, the availability of normative data is essential for interpretation of pathological findings. DTI has been applied by several groups to investigate white matter development in infants and children (Hermoye et al., 2006, Jones et al., 2003, McGraw et al., 2002, Miller et al., 2003, Mukherjee et al., 2001). For this age group, reference data on age-related differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in major fiber tracts recently became available (Hermoye et al., 2006). However, there are very few normative DTI data for children and adolescents. Two previous studies evaluated children in a narrow age range (8–12 years old) (Klingberg et al., 1999, Snook et al., 2005). Voxelwise analyses were used in two studies with a larger number of subjects and a wider age interval (5–18 years (Schmithorst et al., 2002) and 6–19 years (Barnea-Goraly et al., 2005)) to examine age-related differences in ADC and FA. Schmithorst et al. (2002) reported a negative correlation between the trace of the ADC and age throughout the white matter and an increase in FA with age in four fiber tracts (internal capsule, corticospinal tract, left arcuate fasciculus, and right inferior longitudinal fasciculus) while Barnea-Goraly et al. (2005) found more widespread age-related differences in FA in children and adolescents. While voxelwise methods employed in both papers (Barnea-Goraly et al., 2005, Schmithorst et al., 2002) can be used for analyses of the entire brain, they require inter-subject registration and image smoothing, and comprise a large number of statistical tests that may increase Type I errors. In our analyses, we therefore used a region-of-interest (ROI)-based approach similar to that employed in a recent DTI study of early brain development (Hermoye et al., 2006) to assess age-related and hemispheric differences in ADC and FA in 15 selected white matter tracts in healthy children and adolescents.
For follow-up of longitudinal DTI studies, knowledge of measurement reproducibility in ADC and FA is essential in order to predict detectable changes. However, data on reproducibility are limited (Ciccarelli et al., 2003, Pfefferbaum et al., 2003) and no quantitative evaluation of regional differences in ADC and FA reproducibility is available in the literature. Our main goal therefore was to establish reproducibility in pediatric DTI data. We evaluated intra-rater, inter-rater, and between-scan reproducibility of ADC and FA measurements, using two different ROI drawing methods. To our knowledge, this is the first study to evaluate in detail ADC and FA reproducibility, hemispheric differences, and the effect of age in healthy, thoroughly screened children and adolescents using a typical, clinical DTI protocol on a standard 1.5 T scanner.
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Material and methods
Typically developing children and adolescents were recruited from the Baltimore, MD, area by advertisement. Each participant and parent signed a consent form that met the institutional review board standards of the Johns Hopkins Medical Institutions. Participants were initially screened over the telephone and excluded if there was a history of neurological disorder, mental retardation, or learning disability. Parents of those children meeting these eligibility criteria participated in a
Results
Excellent data quality was achieved in all scans. Fig. 3 shows the color maps from the initial examination and the repeated examination in one subject. The four slices used in the ROI analysis show good data quality and good agreement in slice position and fiber tract profile.
The F-test detected smaller variances of ADC and FA obtained by the polygonal method compared to the ellipsoidal approach. For the intra-rater data, the variance in ADC was smaller by 49% on average using the polygonal
Discussion
We investigated reproducibility, hemispheric, and age-related differences in white matter ADC and FA in healthy children and adolescents, using a clinical DTI protocol at 1.5 T. Our approach yielded an excellent intra-rater, inter-rater and between-scan reproducibility for ADC and FA. The high precision of ADC and FA measurements allowed for detection of small age-related differences in this age group. Our results indicate our experimental method and data analysis can be applied to future
Acknowledgments
This study was supported by NIH grant 5RO1 NS042851 and the Johns Hopkins General Clinical Research Center (NIH M01 RR 00052). We thank Dr. Hangyi Jiang, Dr. Craig Jones and Dr. Jonathan Farrell for software support. We also would like to thank Rena Geckle and Amanda Barnes for their help with recruitment of subjects and Cynthia Schultz for help with data acquisition.
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2020, NeuroImageCitation Excerpt :These observations suggest early childhood may be a dynamic maturational period in terms of neurite density and orientation dispersion, though NODDI has yet to be applied to investigate changes in early childhood specifically. White matter maturation is known to occur asynchronously across the brain, though evidence of hemispheric asymmetries in white matter properties and developmental changes across the lifespan are largely inconsistent (Bonekamp et al., 2007; Carper et al., 2016; Dean et al., 2017; Takao et al., 2011; Thiebaut de Schotten et al., 2011). In infants and children, DTI metrics have been shown to have a leftward asymmetry, suggestive of faster left hemisphere maturation (Bonekamp et al., 2007; Dubois et al., 2009; Krogsrud et al., 2016; Ratnarajah et al., 2013).