Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study

AJNR Am J Neuroradiol. 2023 Jul;44(7):776-782. doi: 10.3174/ajnr.A7903. Epub 2023 Jun 15.

Abstract

Background and purpose: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation.

Materials and methods: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation.

Results: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation.

Conclusions: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calcium
  • Humans
  • Inflammation
  • Magnetic Resonance Imaging
  • Microglia*
  • Neuroinflammatory Diseases*
  • Positron Emission Tomography Computed Tomography

Substances

  • Calcium