FV 12. High resolution MR elastography of the hippocampus as a novel biomarker for Alzheimer’s disease?

Background Alzheimer’s disease (AD), the most common cause of dementia, is marked by progressive neurodegenerative changes of brain tissue, which affect the hippocampus early in the course of the disease (1). Whole brain MR elastography (MRE) has been demonstrated to detect decreased overall brain stiffness in AD compared to healthy controls (HC) (2). In this pilot study we investigate whether multifrequency MRE (MMRE) can detect differences in the elasticity of the hippocampus between patients with clinical diagnosis of AD and HC. Methods 14 patients with clinical diagnosis of AD (median age 77 years, 8 females) and 14 age- and sex-matched HC underwent MMRE (3T MRI; Siemens Trio) using a single-shot EPI-based MRE sequence (3). Full 3D wave fields were acquired at 7 mechanical frequencies (30 to 60 Hz, 5 Hz increments) in 16 contiguous coronal slices (8 instances of the wave cycle). For parameter reconstruction, multifrequency dual elasto-visco (MDEV) inversion was applied (3). By this method, two independent parameter maps of the magnitude ( | G ∗ | ) and the phase angle ( ϕ ) of the complex shear modulus are obtained. The Hippocampus and the Thalamus were segmented from the individual T1-structural images (FSL-FIRST, fsl version 4.1) and then co-registered to the native space elasticity parameter maps (FSL-FLIRT). Thirdly, we generated a whole brain white matter (WM) mask directly from the elasticity-maps.Within all masks median values were extracted. Results In the AD-group clinical diagnosis had been established for 3.6 ± 2.2 years. In 9/14 patients, information about CSF-analysis was available; of these 6/9 displayed a typical constellation of the CSF-biomarkers. Patients in the AD-group had a median score of 20 on the Mini-Mental-State-Exam compared to 29 for HC. In the AD group | G ∗ | - and ϕ -values in the hippocampus region were significantly lower than in HC ( | G ∗ | : p ϕ : p = 0.001; Table 1 ). For the thalamus we observed a trend towards lower measures in the AD-group. Within the whole brain WM mask we observed significantly lower measures of | G ∗ | in the AD group (p = 0.016) but not for ϕ (see Table 1 ). Fig. 2 a shows boxplots of | G ∗ | in the three regions. If we postulate | G ∗ | of the Hippocampus as a diagnostic test to differentiate between AD and HC and plot the ROC-curve, this suggests a cutoff of | G ∗ | = 900 Pa( Fig. 2 b). This would provide a sensitivity of 78% and a specificity of 92% with an AuROC-value of 0.92 (95%CI: 0.82–1.00). Discussion Our data confirm that whole brain WM masks show reduced stiffness in patients with AD (2). However, we report for the first time that MMRE is capable of detecting differences in the elasticity of small brain regions such as the Hippocampus. Our data suggest that the stiffness within the Hippocampus is reduced in patients with clinical diagnosis of AD. Since the Hippocampus is involved in neurodegenerative processes early in the course of AD, the detection of decreased hippocampal stiffness could become a biomarker for early diagnosis and progression monitoring. The relatively high specificity observed in our study motivates further investigation whether MMRE can detect decreased brain stiffness already in early stages of the disease such as mild cognitive impairment and whether these changes predict clinical decline.