White Matter Volume and Anisotropy in Preterm Children: A Pilot Study of Neurocognitive Correlates

Abstract

ABSTRACT:The objectives of this study were to evaluate the differences in whole brain white matter (WM) volume and anisotropy between preterm and term children and to determine the relationships with cognitive outcome. Twenty-five low birth weight (BW), preterm, neurologically normal children between 8.8 and 11.5 y of age were recruited for volumetric and diffusion-tensor magnetic resonance imaging (DTI), together with 13 age-matched term control subjects. Subsequent intelligence quotient (IQ) testing was performed for 21 preterm children within 6 mo of imaging studies. We computed the mean volume and fractional anisotropy (FA) of the whole brain WM and compared the differences between the two groups. Mean WM volume and FA were significantly lower in the preterm group (p ϭ 0.014 and p Ͻ 0.001, respectively). Multiple regression analysis found both WM volume and FA to be independent variables significantly affecting full scale IQ (FSIQ) (r 2 ϭ 0.407, p ϭ 0.021 and r 2 ϭ 0.496, p ϭ 0.005, respectively) after adjusting for BW, gestational age (GA), and gender. In the evaluation of the whole brain WM of preterm children, we found that both volume and FA remain reduced at late childhood with both parameters significantly affecting long-term cognitive outcome. N early 90% of very low BW (VLBW) premature infants now survive the neonatal period due to major advances in neonatal intensive care (1). However, approximately 10% of VLBW preterm infants later exhibit cerebral palsy, 30%-50% later manifest neurodevelopmental handicap during their preschool years, and 50% require special help in grade school. Even in the absence of global intellectual deficits, premature infants are at increased risk of learning disabilities, academic difficulties (2,3), and behavioral problems (4,5). Nearly 20% repeat a grade in school by age 8 y (6).With recent advances in magnetic resonance imaging (MRI), subtle brain anomalies are now described in preterm children using qualitative and quantitative MR methods, such as decrease in cortical complexity (7) and decreases in total cortical gray matter (GM) (8 -10) and WM volume (11-13), as well as regional reduced tissue volume (14 -16). Furthermore, an association has been found between some of these abnormalities, such as delay in gyral development being highly related to the presence and severity of WM abnormalities (17). To date, WM volumetric studies in preterm infants and children have demonstrated total WM volume reduction to be significantly correlated with BW (11) and GA (12,18), and some studies further show the adverse effect of regional WM changes on neurocognitive function (19 -21).DTI is a relatively new quantitative MRI technique advantageous for the evaluation of the WM fibers in the brain because it is able to evaluate the directional variability of water diffusion. In WM tracts, the movement of water molecules is relatively free in the direction parallel to its length but restricted in the perpendicular directions by barriers such as axonal membrane and myelin sheaths surroundi...

Young adults born preterm with very low birth weight demonstrate widespread white matter alterations on brain DTI

“…Studies of preterm born children in late childhood also demonstrate significantly reduced FA in various WM tracts. Mean FA values of the whole WM of the brain was significantly decreased in preterm born children at the age of 8-11 years (Yung et al, 2007), and widespread decreases in FA was found in the uncinate fasciculus, the inferior and superior fronto-occipital fasciculus, splenium of corpus callosum, and the external capsule in preterm born children at the age of 12 (Constable et al, 2008). In the current VLBW group decreased FA was shown at 15 years in large WM areas, including the posterior part of cingulum, occipital periventricular WM, superior longitudinal fasciculus, arcuate fasciculus, corpus callosum and capsula interna (Vangberg et al, 2006).…”

“…These micro-structural differences are mainly seen as reductions in FA in central WM regions at term equivalent age (Hüppi et al, 2001). These changes persist through childhood and into adolescence (Anjari et al, 2007;Bassi et al, 2008;Constable et al, 2008;Nagy et al, 2003;Partridge et al, 2004;Rose et al, 2008;Vangberg et al, 2006;Yung et al, 2007). The effects of being born preterm on WM in early adulthood remain to be elucidated.…”

Serial Diffusion Tensor Images during Infancy and Their Relationship to Neuromotor Outcomes in Preterm Infants

“…However, most of the preterm infants had MDI scores within the normal range, similar to the term infants. Cognitive function may have been underestimated in the present study because the assessment of cognitive function was performed at an earlier age than in previous studies [22,23], therefore the diagnosis may be limited [24]. Postnatal infection and chronic lung disease are known risk factors for poor neurodevelopmental outcomes [25,26].…”

A semi-automated method for measuring thickness and white matter integrity of the corpus callosum

“…13 The CC thickness may be secondarily affected by fibre loss, 12 as seen in children after severe hypoxic ischaemic injury, HIV encephalopathy or large infarcts.…”