Abstract
IntroductionT1‐ and T2‐weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1‐weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM‐hyper) volume from FLAIR and white matter hypointensity (WM‐hypo) volume from T1‐weighted images and compared their associations with age and cerebrospinal fluid (CSF) β‐amyloid and tau.MethodsA total of 56 nondemented participants (68–94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM‐hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM‐hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2‐FLAIR.ResultsWM‐hyper and WM‐hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p < .0001). Age was significantly associated with both WM‐hyper (r = .31, p.e. 0.078 ± 0.030, p = .013) and WM‐hypo (r = .42, p.e. 0.055 ± 0.015, p < .001). CSF β‐amyloid levels were predicted by WM‐hyper (r = .33, p.e. −0.11 ± 0.044, p = .013) and WM‐hypo (r = .42, p.e. −0.24 ± 0.073, p = .002). CSF tau levels were not correlated with either WM‐hyper (p = .9) or WM‐hypo (p = .99).ConclusionsStrong correlations between WM‐hyper and WM‐hypo, and similar associations with age, abnormal β‐amyloid, and tau suggest a general equivalence between these two imaging markers. Our work supports the equivalence of white matter hypointensity volumes derived from FreeSurfer for evaluating leukoaraiosis. This may have particular utility when T2‐FLAIR is low in quality or absent, enabling analysis of older imaging data sets.
Highlights
T1‐ and T2‐weighted sequences from magnetic resonance imaging (MRI) often provide useful com‐ plementary information about tissue properties
Neuroimaging is an essential tool in the evaluation of age‐related accumulation of small vessel disease that contributes to vascular insult in the brain, which shows up as white matter lesions
Age is a robust universal predictor of WM lesions, so we evaluated the association of age as independent predictor variables to WM‐hyper and white matter hypointensity (WM‐hypo) as dependent variables, and in a second model, we further adjusted for cognitive status
Summary
Chronic vascular insult is an important biomarker for cognitive im‐ pairment (Gorelick et al, 2011) where damage accumulates silently for decades before the onset of clinically identifiable dementia symptoms (Brown & Thore, 2011). High contrast and high‐resolution T1‐weighted images are the pri‐ mary input requirement for automated brain segmentation programs such as FreeSurfer (Bruce Fischl, 2012) and the related FDA‐approved NeuroQuant (Cortech Labs, San Diego). Both programs report WM‐ hypo volumes, but information of WM‐hypo is less frequently used than WM‐hyper. We sought to assess whether WM‐hypo and WM‐ hyper are equivalent markers of WM damage in normal aging and early neurodegenerative disease by evaluating their associations with age and cerebrospinal fluid (CSF) levels of β‐amyloid and tau. We hypothesized that WM‐hypo and WM‐hyper would be increased with age and would reflect neurodegeneration as revealed by abnor‐ mal CSF β‐amyloid and tau levels
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