On the origin of a potential clearance marker: The contribution of enlarged perivascular fluid diffusion to an MRI derived proxy of interstitial fluid

Abstract

AbstractBackgroundIntraVoxel Incoherent Motion (IVIM) MRI can detect the diffusion of cerebral interstitial fluid (ISF) (D int) and its volume fraction (f int), which has the potential as a proxy of cerebral waste clearance. fint has been suggested to both be driven by fluid diffusivity within enlarged perivascular spaces (ePVS) ‐ transporting fluid from the subarachnoid space into the parenchyma ‐ and the ISF between the parenchymal cells. Both factors play a crucial role in soluble protein clearance, e.g., Amyloid‐Beta (Aβ).This study simultaneously aims to verify the contribution of ePVS fluid diffusivity to fint and highlights the ability to specifically assess ePVS fluid diffusion in the cerebrum using a non‐invasive MR method.MethodTwenty neurotypical elderly subjects (Table 1) underwent ultra‐high field MRI (7T research system, Siemens Healthcare GmbH, Erlangen, Germany) (Table 2).The intermediate diffusion components (Dint) in the range 1.5*10‐3< Diffusivity<4.0*10‐3 mm2/s were calculated using spectral analysis (Fig.1). The relative signal contribution of Dint was quantified by fint.ePVS were segmented from the enhanced perivascular contrast images (Fig.2). Median fint values were extracted from ePVS and non‐ePVS voxels within the basal ganglia (BG).fint and Dint values from within the ePVS mask were compared with values from surrounding non‐ePVS voxels in the BG using Wilcoxon Signed Ranks Tests.ResultFigure 3 contains a graphic summary of the statistical comparison of Dint and fint values from the ePVS and non‐ePVS voxels in the BG. Higher Dint and fint values are observed in the ePVS compared to the non‐ePVS tissue.ConclusionThe current study identified a higher IVIM‐derived proxy of ISF within the ePVS compared to surrounding non‐ePVS tissue, confirming that ePVS indeed contribute to the waste clearance marker fint.ePVS are fluid‐filled spaces surrounding cerebral blood vessels, in which ISF diffusivity is less restricted. This explains the higher Dint values in ePVS compared to non‐ePVS.Furthermore, this study suggests a potential method to investigate diffusivity within the microscopic ePVS, independent of the ISF diffusivity between parenchymal cells. In patients with Alzheimer’s disease, this method could be applied to investigate alterations in ISF diffusivity which could be representative of potential Aβ blockages in ePVS.