A SPECT-based method for dynamic imaging of the glymphatic system in rats

Abstract

The glymphatic system is a brain-wide waste drainage system that promotes cerebrospinal fluid circulation through the brain to remove waste metabolites. Currently, the most common methods for assessing glymphatic function are ex vivo fluorescence microscopy of brain slices, macroscopic cortical imaging, and MRI. While all these methods have been crucial for expanding our understanding of the glymphatic system, new techniques are required to overcome their specific drawbacks. Here, we evaluate SPECT/CT imaging as a tool to assess glymphatic function in different anesthesia-induced brain states using two radiolabeled tracers, [111In]-DTPA and [99mTc]-NanoScan. Using SPECT, we confirmed the existence of brain state-dependent differences in glymphatic flow and we show brain state-dependent differences of CSF flow kinetics and CSF egress to the lymph nodes. We compare SPECT and MRI for imaging glymphatic flow and find that the two imaging modalities show the same overall pattern of CSF flow, but that SPECT was specific across a greater range of tracer concentrations than MRI. Overall, we find that SPECT imaging is a promising tool for imaging the glymphatic system, and that qualities such as high sensitivity and the variety of available tracers make SPECT imaging a good alternative for glymphatic research.

Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

“…However, radiotracers may be used for dynamic scans that are three to four times longer than their half-life. Moreover, a recent study suggested the useful role of radiotracers for in vivo imaging of glymphatic function 47 . We recently introduced another method to assess CSF-to-blood clearance capacity 13 , incorporating an intrathecal injection of a CSF tracer (e.g., gadobutrol), followed by repeated plasma samples.…”

Glymphatic system dysfunction in neurodegenerative diseases

“…This makes developments in noninvasive whole brain imaging technologies and computational analysis of fluid dynamics even more important. While the current most common methods for the assessment of glymphatic function are ex vivo fluorescence microscopy of brain slices and macroscopic cortical imaging with invasive tracer infusion, new techniques like noninvasive MR imaging are required to overcome these specific drawbacks (for a detailed review of current innovations in MR and SPECT imaging [80,81]). Using these techniques, future clinical trials will show whether maintaining vascular structure and function and improvement of glymphatic flow will prevent or delay the onset Alzheimer's disease and Cerebral Amyloid Angiopathy.…”

Dominance of Tau Burden in Cortical Over Subcortical Regions Mediates Glymphatic Activity and Clinical Severity in PSP

“…30 Recently, several methods have been developed that may reveal regional glymphatic activity. [54][55][56] Therefore, the relationship between the DTI-ALPS index and glycemic clearance should be interpreted with caution. The sequential effect among glymphatic dysfunction, tau deposition, and clinical symptoms needs to be verified in longitudinal studies.…”

“…There has been only one study that directly compared glymphatic activity measurement between the intrathecal contrast media administration method and the DTI-ALPS index method 30 . Recently, several methods have been developed that may reveal regional glymphatic activity 54–56 . Therefore, the relationship between the DTI-ALPS index and glycemic clearance should be interpreted with caution.…”