Longitudinal study of sub-regional cerebral viscoelastic properties of 5XFAD Alzheimer's disease mice using multifrequency MR elastography.

PURPOSE: To study sub-regional, longitudinal changes occurring inside brains of 5XFAD mice, an Alzheimer's disease (AD) model, based on viscoelastic parameters derived using MR elastography and their spatial variation.

METHODS

Female 5XFAD and non-transgenic B6SJLF1/J mice as controls (n = 9 for both groups) were used for the study. Scans were performed inside a 9.4T preclinical MRI scanner using SampLe Interval Modulation-magnetic resonance elastography (SLIM-MRE). Experiments were performed at ages 2, 4, and 6 mo, and by using three actuation frequencies: 900, 1000, and 1100 Hz. Multifrequency dual elasto-visco (MDEV) reconstruction was used to combine 3D multifrequency MRE data and calculate magnitude G∗ , and phase angle φ, of the complex shear modulus G∗ . Mean values were measured for the overall brain and sub-regions associated with the early onset of AD, to check for the effect of aging and mouse model. Spatial coefficient of variation (CV) of both parameters across different age-groups were analyzed.

RESULTS

G∗ and φ values reduced with age for overall brain in 5XFAD mice with significant difference in mean G∗ between 5XFAD and control mice at 6 mo (P = .029). Analyzing values from the hippocampal region highlighted drop in mean G∗ and φ values. The CV of G∗ inside hippocampus enabled differentiation at 4 mo with it being significantly lower in 5XFAD mice (P = .0007).

CONCLUSION

Multifrequency 3D MRE revealed longitudinal viscoelastic changes in 5XFAD mice and the CV of G∗ in brain sub-regions may qualify as biomarker for early diagnosis of AD.