MRI investigation of clearance mechanisms of the Glymphatic System

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15m
Poster

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Description

Introduction:
The Glymphatic System has been identified as a metabolic waste products clearance system in the brain, depending on paravascular pathways and the flux of cerebrospinal fluid (CSF). CSF flow elutes soluble proteins and waste, and is intensified during sleep or anesthesia. In our experiments we evaluate the effect of brain state on distribution of contrast agent and water diffusivity.
Methods:
For the measurements we used female Fisher rats and performed MRI under three different anesthetic regimens (Isoflurane (Iso), Medetomidine (Mede) and Iso+Mede) to resolve potential differences in glymphatic clearance originating from different brain states, which were monitored by optical calcium recordings. As contrast agent we use Gadovist, delivered by a modified venous catheter implanted into the Cisterna magna. Apparent diffusion coefficient (ADC) maps and T1 weighted 3D FLASH MRI were acquired during 6 hours. Manually drawn ROIs in CSF-compartments and brain parenchyma were analyzed.
Results:
Signal changes in T1w MRI, originating from distribution of contrast agent, which is indicative of glymphatic activity, were dependent on the anesthetic regimen. Higher signal increase in subarachnoidal space and in cortex and brain stem parenchyma was observed under Mede compared to Iso. Under Mede a significantly lower ADC was observed as compared to Iso. The combination of Iso+Mede, although reproducing a sleep-like brain state as under Iso alone, resulted in high T1w signal (similar to Mede), but low ADC in cortex (similar to Iso).
Discussion:
Our data confirm the assumption that different brain states, induced by different anesthetics, have impact on glymphatic waste clearance. They also suggest a strong influence of CSF production, which is increased under Mede and Iso + Mede. ADC maps support the notion that the lowered diffusion under awake-like brain state (Mede) is possibly caused by an increase of cellular volume of activated neurons and therefore a reduced water volume in the ECM. Those results indicate a less efficient glymphatic clearance in awake-like brain state. Further investigation into the exact pathways of glymphatic clearance under different anesthetic regimens or pharmacological modulation is therefore warranted.

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