SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods

Area of Science:

• Neuroimaging
• Radiochemistry
• Pharmacokinetics

Background:

• Cerebral microglial activation quantification in vivo often uses (R)-[11C]PK11195 PET with plasma input or reference tissue methods.
• Region of interest (ROI) approaches are laborious and prone to interobserver variability, limiting analysis to predefined areas.
• Standard pharmacokinetic models struggle with voxel-wise analysis of (R)-[11C]PK11195 binding due to noise sensitivity.

Purpose of the Study:

• To compare the performance of linearized plasma input and reference tissue parametric methods for statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding.
• To evaluate the sensitivity of different parametric imaging approaches in detecting age-related differences in microglial activation.

Main Methods:

• Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were conducted in healthy younger and elderly subjects.
• Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearized Logan (plasma input) and Reference Parametric Mapping (reference tissue) models.
• Group-level SPM analysis (two-sample t-test) was performed on parametric images, with and without proportional scaling.

Main Results:

• Parametric BP images analyzed without scaling demonstrated the highest sensitivity in detecting age-related differences in (R)-[11C]PK11195 binding.
• Vd images only revealed age-related differences when analyzed with proportional scaling, attributed to intersubject variations in K1/k2.
• Reference tissue parametric mapping (RPS) proved more effective than plasma input models for voxel-wise BP analysis in this context.

Conclusions:

• Linearized reference tissue parametric methods, particularly for binding potential (BP) without scaling, offer a sensitive approach for voxel-wise analysis of (R)-[11C]PK11195 binding.
• This parametric imaging strategy enhances the detection of differences in cerebral microglial activation between subject groups.
• The findings support the use of reference tissue parametric mapping for robust in vivo quantification of neuroinflammation markers.