MR elastography of frontotemporal dementia

Abstract

Several imaging and biofliud biomarkers exist to measure various disease processes associated with frontotemporal dementia (FTD). However, the field is still in need of novel disease biomarkers. Magnetic resonance elastography (MRE) is a noninvasive technique to measure tissue stiffness, akin to manual palpation. Our objective was to investigate the effect of FTD on brain stiffness. We examined 14 subjects with brain MRE including 9 PIB-negative cognitively normal controls (CN), and 5 male subjects with behavioral variant FTD (age range 53–65, mean 60) including monozygotic twins with a mutation in gene encoding progranulin, 2 with mutations in the gene encoding microtubule-associated protein tau and one with the GGGGCC expansion in chromosome 9 open reading frame 72. MRE data were collected with a modified spin-echo EPI pulse sequence resulting in images with 3 mm isotropic sampling and were acquired in just less than 7 minutes. In each subject we measured age adjusted global brain stiffness (entire brain excluding cerebellum), in 8 regions and a summary ROI that included the frontal and temporal lobes but excluded the sensory/motor strip (labeled FT). Group-wise difference in global stiffness demonstrated decreased brain stiffness in FTD (2.59 kPa) compared with NC (2.77 kPa) (p=0.007). Regional differences were most prominent in the frontal lobes (p=0.001) and the temporal lobes (p=0.005). Stiffness did not differ by group in the parietal or occipital lobes or the pre- and post-central gyri. Based on these results, a summary ROI composed of the frontal and temporal lobes but excluding the sensory/motor areas was generated which obtains complete separation between the two groups. Figure 1 shows a boxplot of stiffness. It has been previously reported that global brain stiffness is decreased in subjects with AD [1]. We now report a specific pattern of fronto-temporal stiffness reduction in FTD, expanding the diagnostic utility of this novel biomarker of neurodegenerative disease.