MRI detection of impairment of glymphatic function in rat after mild traumatic brain injury

Aug 21, 2020Brain research

MRI shows reduced brain waste clearance after mild brain injury in rats

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Abstract

Mild traumatic brain injury (mTBI) was associated with significantly reduced infusion and clearance rates of a contrast agent in the glymphatic pathway.

mTBI resulted in chronic changes in the influx and efflux of the contrast agent used to assess glymphatic function.
Significantly increased clearance time constants were observed in mTBI animals compared to healthy controls.
The efficiency of glymphatic function was reduced in multiple brain regions following mTBI.
Heterogeneous effects of mTBI on glymphatic function were noted across different anatomical regions.
Dynamic contrast-enhanced MRI combined with advanced kinetic analysis may facilitate objective assessment of mTBI.

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We investigated the effect of mild traumatic brain injury (mTBI) on the glymphatic pathway using contrast-enhanced magnetic resonance imaging (CE-MRI) and quantified with kinetic parameters obtained from an advanced two-compartment model. mTBI was induced in male Wistar rats using a closed head impact. Animals with and without mTBI (n = 7/group) underwent the identical MRI protocol 10-weeks post-injury, including T2-weighted imaging and 3D T1-weighted imaging with intra-cisterna magna injection of contrast agent (Gd-DTPA). The parameters of infusion rate, clearance rate and clearance time constant, characterizing the kinetic features of glymphatic tracer transport in a living brain, were quantified in multiple brain tissue regions. In the majority of examined regions, our quantification demonstrated significantly reduced infusion and clearance rates, and significantly increased clearance time constant in the mTBI animals compared to the healthy controls. These data indicate that mTBI induces chronic changes in influx and efflux of contrast agent and glymphatic pathway dysfunction. While the reduced efficiency of glymphatic function after mTBI was apparent in brain, regional evaluation revealed heterogeneous glymphatic effects of the mTBI in different anatomical regions. The suppression of glymphatic function, rather than the presence of focal lesions, indicates a persistent injury of the brain after mTBI. Thus, dynamic CE-MRI in conjunction with advanced kinetic analysis may offer a useful methodology for an objective assessment and confirmatory diagnosis of mTBI.

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MRI detection of impairment of glymphatic function in rat after mild traumatic brain injury

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