Non-invasive MRI of choroid plexus-cerebrospinal fluid water exchange using multi-TE FLAIR

The choroid plexus (CP), or blood-cerebrospinal fluid barrier, performs unique and diverse roles in support of brain homeostasis. Novel and non-invasive imaging biomarkers of choroid plexus physiology may be useful to further our understanding of its role in the development of pathology. Here, we introduce the concept of measuring water exchange between the choroid plexus tissue and the proximal CSF using a multiple TE fluid-suppressed (FLAIR) acquisition. By fitting the MRI signal at the choroid plexus acquired with a multi-TE FLAIR readout to a two-compartment bi-exponential model, we observed that the slow decaying T2 component of the signal had a T2 highly similar to that of cerebrospinal fluid (CSF). This finding, in turn, provides evidence that, paradoxically, this signal derives from CSF in a FLAIR image. The specific spatial co-localization of this long-T2 signal to the CP within the lateral ventricles provides evidence that this reflects the exchange of water molecules between the CP tissue and the CSF during the inversion time. A reduction in choroid plexus-CSF water exchange rate was then detected in the aged vs. young mouse brain using this method. Preliminary application of the method to the human brain at 3T, however, yielded weaker results which suggest that the method may not be able to capture this phenomenon clinically with equivalent sensitivity. Nonetheless, in pre-clinical studies, this novel MRI contrast mechanism provides a specific and quantitative signature of choroid plexus physiology and thus may represent a useful non-invasive imaging biomarker of CP dysfunction.