Multimodal imaging findings in normal-appearing white matter of leucoaraiosis: a review

Abstract

Leucoaraiosis (LA), also referred to as white matter hyperintensities (WMHs), are usually seen as patchy or confluent hyperintense areas on T2-weighted or fluid-attenuated inversion recovery MRI in the elderly. It is often asymptomatic in its early stages, yet its persistent evolution to more advanced stages may lead to substantial neurological dysfunction including dementia, stroke and death. Despite its clinical significance, the pathogenic mechanisms underlying LA development are uncertain. In patients with LA, the pathophysiological changes in white matter (WM) are suggested to be continuous from WMHs to its neighbourhood ‘normal-appearing white matter (NAWM)’ on conventional MRI sequences. Multimodal imaging studies revealed that the so-called ‘NAWM’ was actually abnormal with regard to underlying haemodynamic and microstructural changes. On the basis of positron emission tomography CT, xenon-CT, perfusion MRI, etc, the cerebral blood flow of NAWM was found to be significantly reduced in patients with LA, compared with healthy controls. Meanwhile, the integrity of microstructures and blood–brain barrier in NAWM was also demonstrated to be impaired with diffusion tensor imaging and dynamic contrast-enhanced MRI studies, respectively. In addition,the integrity of NAWM correlated much stronger with cognitive performance than did WMHs load. It is reasonable to assume that the subtle injury of NAWM would be more reversible than WMHs themselves. Therefore, multimodal imaging modalities could be appropriately applied to future interventional studies targeting at early pathophysiological changes of NAWM. In this paper, we summarise current knowledge about NAWM of LA mainly acquired from multimodal imaging studies in vivo, and attempt to give options for future work.

White matter hypointensities and hyperintensities have equivalent correlations with age and CSF β‐amyloid in the nondemented elderly

“…In future longitudinal studies, we will assess whether WM‐hypo later spread to involve areas that currently only demonstrate WM‐hyper. Though WM‐hyper is nonspecific and associated with many factors, age is consistently the strongest predictor of lesion accumulation in community‐based studies (King, Chen, et al, ; Zhong & Lou, ). We found the expected linear correlation between larger WM‐hyper and WM‐hypo (Figure ) volume with greater age.…”

Venous disruption affects white matter integrity through increased interstitial fluid in cerebral small vessel disease

“…11 Besides, CSVD-related white matter damage is not confined to WMH region but spread widely to normal appearing white matter. 12,13 Thereby, WMH cannot accurately represent white matter damage. Analyzing the white matter in DMVs drainage area with imaging techniques that can reflect microstructural changes would provide more solid evidence for the DMVs disruption-related white matter damage in CSVD.…”

Predicting the Development of Normal-Appearing White Matter With Radiomics in the Aging Brain: A Longitudinal Clinical Study

“…Normal-appearing white matter refers to the areas around the WMH that appear normal on conventional magnetic resonance images, yet may already display low perfusion or microstructural changes ( Maillard et al, 2011 ; Fu et al, 2014 ; Maillard et al, 2014 ; Pelletier et al, 2015 ; Zhong and Lou, 2016 ). A previous study found a stronger association between the disruption of NAWM integrity and psychomotor dysfunction when compared with WMH load ( Hirsiger et al, 2017 ).…”