Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling

Abstract

Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40 and 84 % respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the ‘frontal ageing’ hypothesis, there was a significant positive correlation between mean diffusivity (〈D〉) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between 〈D〉 and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity.

Neuroprotective lifestyles and the aging brain

“…36 Tractaveraged water diffusion parameters were obtained using a fully automated tract segmentation technique, PNT, which removes the dependence of tractography output on the potentially subjective placement of seed points within tracts of interest. 21,23 Although atrophy and WML volumes were obtained using a validated semiautomatic method, 26 such methods are insensitive to subtle visually detectable variations and lack of specificity in expressing rele- vant information like lesion location. Qualitative measures are therefore sometimes preferred.…”

“…Tract-averaged ͳDʹ and FA values, weighted by the connection probability, were determined for 12 tracts of interest using probabilistic neighborhood tractography (PNT) with the BedpostX/ProbTrackX algorithm, 20 a novel approach for automatic segmentation of major white matter pathways. [21][22][23][24][25] Tracts assessed were the genu and splenium of corpus callosum, bilateral anterior thalamic radiations, rostral cingulum bundles, and bilateral arcuate, uncinate, and inferior longitudinal fasciculi.…”

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…However, additional studies have verified the global decline of FA with age (Hsu et al 2010), with an antero-posterior gradient of susceptibility Minati et al 2007). Moreover, DTI studies that examined the effects of WMH, ventriculomegaly, and brain atrophy found these to contribute to a decline of FA with age (Bastin et al 2010). Although WM lesions with age are exacerbated by hypertension, these appear in more posterior regions, a pattern distinct from normal aging (Kennedy and Raz 2009a).…”

Partial volume effect as a hidden covariate in DTI analyses

“…The developing/aging brain, in particular, has been the research topic of many investigations, 1 with studies including subjects ranging from neonates to aging adults. It has been shown repeatedly that the FA of several WM regions (e.g., the cingulum bundles and the uncinate fasciculi) increases during maturation and subsequently decreases with age above the age of approximately 30 years (Bastin et al, 2010;Hasan et al, 2009;Hsu et al, 2008Hsu et al, , 2010Jones et al, 2006;Lebel et al, 2008, in press;Sala et al, in press, 2005;Voineskos et al, 2010, in press). Most of these studies also show an inverse relationship (decrease followed by increase) for the mean diffusivity (MD) and link these diffusion changes to differences in microstructural organization within the WM (Dubois et al, 2008;Lebel et al, 2008).…”