Differential White Matter Maturation from Birth to 8 Years of Age

Abstract

Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0-8 years and 31 children with autistic spectrum disorder (ASD) aged 2-7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0-8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0-8 years provide reference standards for biomarker detection of neuropsychiatric disorders.

Keywords: 0–8 years; autism; differential maturation; diffusion tensor imaging (DTI); exponential; white matter.

Figure 1

Parcellation of the WM skeleton into five tract groups. (A) The skeleton of the entire WM in coronal (left), axial (middle), and sagittal (right) view after setting the FA threshold 0.2; (B) 3D reconstructed commissural, brainstem, projection, limbic, and association tract groups in sagittal view; (C) parcellation of the WM skeleton into five tract groups with the tract group colors consistent to those shown in (B).

Figure 2

(A) Representative axial OEC, FA, MD, RD, and AD maps at the level of the internal capsule from a representative 2-, 13-, 24-, 48-, and 95-month-old child from top to bottom. (B) The diagram shows hypothesized association between cellular processes (axonal growth, axonal packing, and myelination) and DTI metric changes during WM development.

Figure 3

Differential microstructural maturational curve across all major WM tracts and tract groups measured with FA (A), MD (B), RD (C), and AD (D) measurements. Fitted exponential curves are shown for all tracts and tract groups. The fitted curves of DTI metric measurements averaged from the tract group were plotted in solid line and those from individual WM tracts were plotted in semitransparent dashed lines in the same color.

Figure 4

Three phases (fast, intermediate, and slow phases) identified from fitted exponential maturational FA curve of the averaged entire WM (A) and a representative tract, namely GCC (B), SCP (C), SS (D), FX (E), and CST(F), from each of five tract groups. The ages t1 and t2 when the (FÂ(t)—FÂ (age = 0 year)) value reaches the 2/3 and 8/9 of the (FÂ(age = 8 years)—FÂ (age = 0 year)) value in each fitted exponential curve were used to separate the WM maturation into three phases: fast, intermediate, and slow phases. Please see the Materials and Methods section for abbreviations of WM tract names.

Figure 5

Illustration of percentage increase of FA from 0 to 8 years (with the percentage increase values listed in Table 1), three phases (with the start/end ages and phase length listed in Tables 2) and estimated fitting parameters a, b, and c of exponential curves of FA across all major WM tracts and tract groups. Measures of averaged entire WM were used as the reference. On the left panel, the WM maturation of every WM tract and tract group was displayed in three phases (fast, intermediate, and slow phases), with the boundaries of the three phases of the entire WM displayed as two reference dashed lines. The color bar encodes the percent increases of FA from 0 to 8 years. ^* indicates significant difference of a fitting parameter a, b, or c from that of the averaged entire WM, shown as black dashed lines. ^* placed on the left side indicates the abs(a), b, or c is significantly smaller than that of the entire WM’s, and vice versa. Please see the Materials and Methods section for abbreviations of WM tract names.

Figure 6

Illustration of percentage increase of MD from 0 to 8 years (with the percentage decrease values listed in Table 1), three phases (with the start/end ages and phase length listed in Table 3) and estimated fitting parameters a, b, and c of exponential curves of MD across all major WM tracts and tract groups. Measures of averaged entire WM were used as the reference. On the left panel, the WM maturation of every WM tract and tract group was displayed in three phases (fast, intermediate, and slow phases), with the boundaries of the three phases of the entire WM displayed as two reference dashed lines. The color bar encodes the percent decreases of MD from 0 to 8 years. ^* indicates significant difference of a fitting parameter a, b, or c from that of the averaged entire WM, shown as the black dashed lines. ^* placed on the left side indicates that the fitting parameter a, b, or c is significantly smaller than the entire WM’s, and vice versa. With nonsignificant (n.s.) exponential fitting (R² < 0.223) of MD measurements of SCP, the percentage change of this specific tract is not available (shown in gray) and fitting parameters a, b, and c are not shown. Please see legend of Figure 1 for abbreviations of WM tract names.

Figure 7

Illustration of percentage increase of RD from 0 to 8 years (with the percentage decrease values listed in Table 1), three phases (with the start/end ages and phase length listed in Table 4), and estimated fitting parameters a, b, and c of exponential curves of RD across all major WM tracts and tract groups. Measures of averaged entire WM were used as the reference. On the left panel, the WM maturation of every WM tract and tract group was displayed in three phases (fast, intermediate, and slow phases), with the boundaries of the three phases of the entire WM displayed as two reference dashed lines. The color bar encodes the percent decreases of RD from 0 to 8 years. ^* indicates significant difference of a fitting parameter a, b, or c from that of the averaged entire WM, shown as the black dashed lines. ^* placed on the left side indicates that the fitting parameter a, b, or c is significantly smaller than the entire WM’s, and vice versa. Please see legend of Figure 1 for abbreviations of WM tract names.

Figure 8

Illustration of percentage increase of AD from 0 to 8 years (with the percentage decrease values listed in Table 1), three phases (with the start/end ages and phase length listed in Table 5) and estimated fitting parameters a, b, and c of exponential curves of AD across all major WM tracts and tract groups. Measures of averaged entire WM were used as the reference. On the left panel, the WM maturation of every WM tract and tract group was displayed in three phases (fast, intermediate, and slow phases), with the boundaries of the three phases of the entire WM displayed as two reference dashed lines. The color bar encodes the percent decreases of AD from 0 to 8 years. ^* indicates significant difference of a fitting parameter a, b, or c from that of the averaged entire WM, shown as the black dashed lines. ^* placed on the left side indicates that the fitting parameter a, b, or c is significantly smaller than the entire WM’s, and vice versa. With nonsignificant (n.s.) exponential fitting (R² < 0.223) of AD measurements of PCT, ICP, UF, CGH, CST, and brainstem tract group, the percentage changes of these specific tracts/tract group are not available (shown in gray) and fitting parameters a, b, and c are not shown. Statistical comparisons of the fitting parameters between SCP/ML and those of averaged entire WM were not conducted due to opposite percentage change directions of AD measurements for these two tracts. Please see legend of Figure 1 for abbreviations of WM tract names.