Alzheimer's Imaging Consortium.

Area of Science:

• Neuroimaging
• Biophysics
• Alzheimer's Disease Research

Background:

• Myelin degeneration is implicated in Alzheimer's Disease (AD), but quantifying these changes is challenging.
• Diffusion MRI and X-ray scattering offer complementary sensitivity to myelin structure.

Purpose of the Study:

• To utilize advanced diffusion MRI metrics and X-ray scattering to detect and quantify myelin degeneration in an ex vivo Alzheimer's Disease mouse model.
• To compare the sensitivity of diffusion MRI and X-ray scattering in detecting myelin changes in white and gray matter.

Main Methods:

• Acquisition of diffusion MRI and X-ray scattering data from hAPP mutant and wild-type mouse brains.
• Application of advanced diffusion metrics (e.g., RD, AWF, RK) and X-ray scattering tomographic reconstruction for myelin quantification.
• Non-linear registration to the Allen Atlas and statistical comparison of white and gray matter regions between groups.

Main Results:

• Diffusion MRI revealed myelin degeneration in white matter (increased RD, reduced AWF, reduced RK) in AD mice.
• X-ray scattering showed trends consistent with white matter myelin degeneration and detected significantly lower myelin levels in gray matter (cortex, thalamus).
• Diffusion MRI did not show clear trends in gray matter, highlighting X-ray scattering's sensitivity in these regions.

Conclusions:

• Both white and gray matter showed imaging evidence of compromised myelin in AD mice.
• Diffusion MRI was more sensitive for white matter myelin changes, while X-ray scattering detected gray matter myelin loss.
• X-ray scattering may detect subtle myelin degeneration in gray matter where MRI sensitivity is limited due to complex microstructure.