Quantification of amyloid beta and tau PET without a structural MRI

Area of Science:

• Neuroimaging
• Radiochemistry
• Biomarkers

Background:

• Positron emission tomography (PET) imaging is crucial for quantifying amyloid beta (Aβ) and tau pathologies in Alzheimer's disease (AD).
• Reliance on magnetic resonance imaging (MRI) for PET image coregistration and quantification can limit the generalizability of findings across different research sites and scanners.
• Developing MRI-free quantification methods is essential for standardizing PET imaging protocols and broadening their clinical and research applications.

Purpose of the Study:

• To evaluate the accuracy and reliability of various MRI-free quantification techniques for amyloid beta (Aβ) and tau PET imaging.
• To compare MRI-free quantification results against established MRI-dependent methods, assessing both cross-sectional and longitudinal data.
• To determine if MRI-free approaches preserve the detection of AD-related signals and group differences.

Main Methods:

• Compared MRI-free and MRI-dependent quantification of Aβ PET ([18F]florbetapir, [18F]florbetaben) and tau PET ([18F]flortaucipir) in large cohorts (N=1290 for [18F]florbetapir, N=290 for [18F]florbetaben, N=768 for [18F]flortaucipir).
• Assessed continuous and dichotomous agreement, effect sizes between Alzheimer's disease (AD)-impaired and unimpaired groups, and longitudinal standardized uptake value ratio (SUVR) slopes.
• Utilized cross-sectional and longitudinal data to validate the performance of MRI-free quantification methods.

Main Results:

• The optimal MRI-free methods demonstrated high agreement (R² ≥0.95; ± agreement ≥92%) with MRI-dependent SUVRs for Aβ PET and temporal tau PET ([18F]flortaucipir).
• Effect sizes for differentiating AD-related groups were well-preserved using MRI-free quantification.
• Agreement was slightly reduced for entorhinal tau PET and longitudinal SUVR slopes compared to temporal tau PET.

Conclusions:

• MRI-free quantification of Aβ and tau PET images provides a reliable alternative to MRI-dependent methods.
• These MRI-free approaches effectively maintain the detection of baseline and longitudinal AD-related signals.
• The findings support the broader adoption of MRI-free PET quantification for enhanced generalizability in AD research and potentially clinical settings.