A method for personalized brain mapping of neuroinflammation using 11C-DPA-713 PET

Objectives To facilitate personalized study of neuroinflammation by PET using the TSPO-targeted radiopharmaceutical 11C-DPA-713, we built a parametric image atlas based on healthy subjects and demonstrated its utility in brain mapping by voxel-level z-scoring of individuals with potential neuroinflammation.

Methods Healthy volunteers (n = 12) were imaged with dynamic 11C-DPA-713 PET [1, 2] and parametric images of distribution volume (Vt) were generated applying the Logan method. A normalization approach was devised to compensate for the effects of TSPO gene polymorphism [3] and other factors [4] affecting intra-subject reproducibility and inter-subject variation. All normalized Vt images of healthy subjects were warped to a standard brain space, generating population mean and standard deviation (SD) images to complete the atlas. Utilizing this, the Vt images of several subjects suffering from putative neuroinflammation (former NFL players: N=4, HIV+ patients: N=7) were processed and analyzed by calculating voxel-level z-scores, providing individual whole brain mapping indicative of potential disease-related neuroinflammation.

Results With the individual mean Vt value from gray matter used in normalization, the normalized Vt images demonstrated much improved intra-class correlation among healthy subjects, allowing generation of an atlas with reasonable SDs. Individuals with putative brain inflammation showed large z-scores (> 4) in various brain regions, indicating localized disease.

Conclusions We have developed an approach that may enable construction of a normal brain atlas for TSPO PET imaging and improve the sensitivity of personalized imaging studies of neuroinflammation. We have demonstrated the utility of this method in 11C-DPA-713 PET imaging of both healthy subjects and those with putative neuroinflammation.

Research Support We thank the support from NFL Charities and NIH Grant 5R21MH082277.