Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer

Area of Science:

• Neuroscience
• Biomedical Imaging
• Fluid Dynamics

Background:

• Neurodegenerative diseases like Alzheimer\'s involve protein aggregation and neuronal dysfunction.
• The glymphatic system clears waste products, including amyloid-beta, from the brain.
• Assessing glymphatic function is crucial for predicting neurodegenerative disease risk and progression, but clinical methods are lacking.

Purpose of the Study:

• To evaluate the feasibility of using lumbar intrathecal infusions of cerebrospinal fluid (CSF) tracers to assess glymphatic pathway function.
• To compare the efficacy of lumbar vs. intracisternal infusions for delivering CSF tracers to the brain parenchyma.

Main Methods:

• Ex vivo fluorescence imaging of rat and mouse brain slices after intrathecal infusion of low (3 kDa) and high (500 kDa) molecular weight tracers.
• Quantification of tracer influx into various brain regions following lumbar and intracisternal infusions.
• Analysis of tracer distribution in perivascular spaces and brain interstitium.

Main Results:

• Lumbar intrathecal infusion of low molecular weight tracers allowed entry into the brain along perivascular pathways and exchange with interstitial fluid.
• High molecular weight tracers remained confined to perivascular spaces following lumbar infusion.
• Lumbar infusions resulted in delayed and reduced peak fluorescence in brain parenchyma compared to intracisternal infusions.

Conclusions:

• Lumbar intrathecal contrast delivery is a viable method for assessing glymphatic pathway function.
• This approach, combined with dynamic contrast-enhanced MRI, offers a potential clinical tool for evaluating glymphatic function in humans.
• This technique may aid in the early detection and monitoring of neurodegenerative diseases.