A local-neighborhood Lassen plot filter for creating occupancy and non-displaceable binding images

Area of Science:

• Neuroimaging
• Pharmacology
• Biophysics

Background:

• The Lassen plot is a method for estimating receptor occupancy by drugs using PET imaging when a reference region is unavailable.
• Spatial variations in binding potential can introduce bias in traditional Lassen plot analyses.
• Developing methods to accurately assess drug occupancy in the presence of spatial heterogeneity is crucial for quantitative PET imaging.

Purpose of the Study:

• To introduce and validate a Lassen plot filter for robust estimation of drug-induced receptor occupancy in PET imaging.
• To overcome the limitations of the conventional Lassen plot in handling spatial variations in binding potential.
• To compare the performance of the Lassen plot filter against conventional methods using simulated and real PET data.

Main Methods:

• Simulated PET image data with controlled regional variations in binding potential and non-specific binding were generated.
• The Lassen plot filter was applied to local neighborhoods within PET images at both region of interest (ROI) and voxel levels.
• Performance was evaluated by comparing estimates from the Lassen plot filter, conventional Lassen plot, and change in binding potential (BPND) in simulated and [11C]flumazenil human PET studies.

Main Results:

• The Lassen plot filter provided unbiased estimates of receptor occupancy, even with regional variations in binding potential or non-specific binding.
• Conventional Lassen plot and BPND methods showed bias in the presence of spatial heterogeneity.
• Analysis of human [11C]flumazenil data demonstrated regional variations in occupancy consistent with radioligand and drug distribution.

Conclusions:

• The local-neighborhood Lassen plot filter offers a robust and unbiased approach for estimating drug receptor occupancy from PET data.
• This method eliminates the need for user intervention, improving the reliability of quantitative PET analyses.
• The Lassen plot filter is a valuable tool for accurate assessment of drug effects in neuroimaging studies.