Brain volume findings in 6-month-old infants at high familial risk for autism

Abstract

Objective: Individuals with autism as young as 2 years have been observed to have larger brains than healthy comparison subjects. Studies using head circumference suggest that brain enlargement is a postnatal event that occurs around the latter part of the first year. To the authors' knowledge, no previous brain imaging studies have systematically examined the period prior to age 2. In this study they used magnetic resonance imaging (MRI) to measure brain volume in 6-month-olds at high familial risk for autism.

Method: The Infant Brain Imaging Study (IBIS) is a longitudinal imaging study of infants at high risk for autism. This cross-sectional analysis compared brain volumes at 6 months of age in high-risk infants (N=98) and infants without family members with autism (N=36). MRI scans were also examined for radiologic abnormalities

Results: No group differences were observed for intracranial, cerebrum, cerebellum, or lateral ventricle volume or for head circumference.

Conclusions: The authors did not observe significant group differences for head circumference, brain volume, or abnormalities in radiologic findings from a group of 6-month-old infants at high risk for autism. The authors are unable to conclude that these abnormalities are not present in infants who later go on to receive a diagnosis of autism; rather, abnormalities were not detected in a large group at high familial risk. Future longitudinal studies of the IBIS study group will examine whether brain volume differs in infants who go on to develop autism.

Figure 1. Brain segmentation at six months of age

Figure 1 displays T1w and T2w axial MRI images of a 6 month infant are displayed in panels 1 and 2, in panel 3 with label maps for total brain (yellow) and CSF (blue) segmentations, and in panel 4 with a 3-D rendering of intracranial volume (ICV) (back, blue) and brain surface (front, yellow).

Figure 2. Grading of subarachnoid spaces (SAS) and periventricular spaces (PVS)

The image on the left demonstrates mild enlargement of the subarachnoid spaces. Minimal enlargement is defined as one vessel width of SAS and brain that does not touch the inner table of the calvaria on multiple consecutive sections. Mild SAS has a vessels floating in CSF space over the convexities more than one vessel thick. Moderate enlargement of the SAS extends to significantly enlarge the CSF space between the hemispheres along the falx cerebri. Marked enlargement of the SAS would be profound pathological enlargement for the CSF spaces over and between the hemispheres. The image on the right demonstrates mild enlargement of the perivascular spaces. Minimal enlargement of the PVS is defined as fewer than 5 small, linear T2 hyperintensities or 1–2 larger foci. Mild enlargement is 5–10 small, linear or 3–5 larger, rounded hyperintensities. Moderate enlargement of the PVS is when there are more than 10 linear or 5–10 larger, rounded hyperintensities. Marked enlargement of the PVS involves pathological number, size and location (e.g., corpus callosum) of the hyperintensities associated with white matter volume loss.

Figure 3. Boxplots of head circumference and total brain volumes for HR and LR subjects

Figure 3 shows plots of head circumference (panel 1), intracranial volume (ICV) (panel 2), and total tissue volumes for cerebrum (panel 3) and cerebellum (panel 4). Head circumference is displayed in centimeters (cm) and brain volumes shown in centimeters squared (cm³).

Figure 4

Scatterplots of head circumference and intracranial volume for HR and LR subjects.