Abstract
Background: Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden.Methods: MRTA was applied to T2 weighted high-resolution MR images of nine 8.5-month-old rTg4510 tau pathology (TG) mice and 16 litter matched wild-type (WT) mice. MRTA comprised of the filtration-histogram technique, where the filtration step extracted and enhanced features of different sizes (fine, medium, and coarse texture scales), followed by quantification of texture using histogram analysis (mean gray level intensity, mean intensity, entropy, uniformity, skewness, standard-deviation, and kurtosis). MRTA was applied to manually segmented regions of interest (ROI) drawn within the cortex, hippocampus, and thalamus regions and the level of tau burden was assessed in equivalent regions using histology.Results: Texture parameters were markedly different between WT and TG in the cortex (E, p < 0.01, K, p < 0.01), the hippocampus (K, p < 0.05) and in the thalamus (K, p < 0.01). In addition, we observed significant correlations between histological measurements of tau burden and kurtosis in the cortex, hippocampus and thalamus.Conclusions: MRTA successfully differentiated WT and TG in brain regions with varying degrees of tau pathology (cortex, hippocampus, and thalamus) based on T2 weighted MR images. Furthermore, the kurtosis measurement correlated with histological measures of tau burden. This initial study indicates that MRTA may have a role in the early diagnosis of AD and the assessment of tau pathology using routinely acquired structural MR images.
Highlights
The pathophysiological processes in Alzheimer’s disease (AD), and the formation of the two pathogenic hallmarks of the disease, are thought to begin many years before clinical diagnosis (Jack et al, 2010)
Histology In transgenic strain rTg4510 (TG) animals, each anatomical region selected for analysis had a varying degree of tau pathology (Figures 2A–D)
The TG group had significantly lower entropy whereas kurtosis, mean intensity, uniformity, and skewness were significantly higher in TG group
Summary
The pathophysiological processes in Alzheimer’s disease (AD), and the formation of the two pathogenic hallmarks of the disease (amyloid β and tau accumulations Morris et al, 2001), are thought to begin many years before clinical diagnosis (Jack et al, 2010). Quantitative magnetic resonance imaging texture analysis (MRTA) has been used to derive heterogeneity information in cerebral tissue by extracting texture descriptors from structural MR in AD (Freeborough and Fox, 1998; Torabi et al, 2006; De Oliveira et al, 2011) as well as other neurological disorders (Ganeshan et al, 2010; Radulescu et al, 2013a; Sanz-Cortes et al, 2013; Suoranta et al, 2013) It is currently unknown, precisely how these texture descriptors relate to tau pathology, one of the two major proteinopathies associated with AD development. We examined the potential of MRTA to identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden
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