Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region

Area of Science:

• Neuroimaging
• Alzheimer's Disease Research
• Radiopharmaceutical Imaging

Background:

• Subcortical white matter is generally unaffected by amyloid deposition in Alzheimer's disease (AD).
• Accurate quantification of radiotracer binding is crucial for understanding AD pathophysiology.
• The cerebellum has been a common reference region in PET studies.

Purpose of the Study:

• To investigate the utility of subcortical white matter as a reference region for quantifying [(18)F]FDDNP binding in the human brain.
• To assess the accuracy and reliability of using subcortical white matter compared to the cerebellum.

Main Methods:

• Dynamic [(18)F]FDDNP PET scans were conducted on control subjects and AD patients.
• Simplified reference tissue modeling was used to derive population efflux rate constants (k(')(2)) from subcortical white matter and cerebellum.
• Logan and simplified reference tissue methods were employed to estimate distribution volume ratios (DVRs), using both white matter and cerebellum as reference regions.
• Discriminant analysis was performed for classification of control and AD subjects.

Main Results:

• Subcortical white matter showed lower variability in individual k(')(2) estimates compared to the cerebellum.
• Logan DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly elevated in AD patients.
• Discriminant analysis using regional DVRs achieved accurate classification of control and AD subjects, comparable to using the cerebellum as a reference.

Conclusions:

• Subcortical white matter is a suitable reference region for quantitative [(18)F]FDDNP analysis using the Logan method.
• Employing subcortical white matter can lead to more accurate and less biased binding estimates.
• A pre-determined population efflux rate constant for white matter is necessary for this approach.