Choroid Plexus calcification correlates with cortical microglial activation in humans: a multimodal PET, CT, MRI study

Abstract

ABSTRACTBackgroundChoroid plexus (CP) within brain ventricles is well-known to produce CSF. Additional important CP functions are now recognized including critical modulation of inflammation. Recent MRI studies have demonstrated CP enlargement in human diseases including Multiple Sclerosis and Alzheimer’s Disease, and in association with neuroinflammation measured using translocator protein (TSPO) PET. The basis of MRI-visible CP enlargement is unknown.PurposeBased on tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously-unmeasured calcium within CP contributes to MRI-measured CP volume, and may be more specifically associated with neuroinflammation.Materials and MethodsWe performed a retrospective analysis of PET-CT studies performed between 2013-2019 on a single scanner using the TSPO radiotracer 11C-PK11195. Subjects included controls (n=43) and patients diagnosed with several non-inflammatory neuropsychiatric conditions (n=46.) Cortical inflammation / microglial activation was quantified as non-displaceable Binding Potential (BPnd.) CP and ventricle volume were measured using Freesurfer. CP calcium was measured semi-manually via tracing of low-dose CT acquired with PET and automatically using a new CT/MRI method. The contribution of CP calcium, CP overall volume, ventricle volume, subject age, sex and diagnosis to BPnd was assessed using linear regression.Results89 subjects (mean age 54+/-7 years; 52 men) were included. Fully-automated CP calcium quantification was accurate (ICC with semi-manual tracing = .98.) The significant predictors of cortical neuroinflammation were subject age (p=.002) and CP calcium volume (p=.041), but not ventricle or CP volume.ConclusionCP calcium volume can be accurately measured using low-dose CT acquired routinely with PET-CT. CP calcification – but not CP overall volume – was associated with cortical inflammation. Unmeasured CP calcification may be relevant to recent reports of CP enlargement in human inflammatory and other diseases. CP calcification may be a specific and relatively easily-acquired biomarker for neuroinflammation and CP pathology.Key ResultsChoroid plexus (CP) calcification volume can be reliably quantified using semi-manual tracing on low-dose CT acquired with PET-CT, and fully automatically using our new, accurate (ICC with semi-manual tracing = .98) CT/MRI method.CP calcification and age –but not overall CP volume– significantly predicted 11C-PK11195 PET-measured cortical neuroinflammation in 89 subjects.CP calcification is a relatively easily-assessed, previously-overlooked potential biomarker for neuroinflammation and CP pathology.