TY - JOUR

T1 - A SPECT-based method for dynamic imaging of the glymphatic system in rats

AU - Sigurdsson, Björn

AU - Hauglund, Natalie L.

AU - Lilius, Tuomas O.

AU - Mogensen, Frida L.H.

AU - Mortensen, Kristian N.

AU - Beschorner, Natalie

AU - Klinger, Laura

AU - Bærentzen, Simone L.

AU - Rosenholm, Marko P.

AU - Shalgunov, Vladimir

AU - Herth, Matthias

AU - Mori, Yuki

AU - Nedergaard, Maiken

N1 - Funding Information: Funding was provided by Lundbeck Foundation grant R386-2021-165, Novo Nordisk Foundation grant NNF20OC0066419, National Institutes of Health grant R01AT011439, National Institutes of Health grant U19NS128613, US Army Research Office grant MURI W911NF1910280, Human Frontier Science Program grant RGP0036, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Simons Foundation grant 811237. Acknowledgements

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - cerebrospinal fluid dynamics

KW - lymph nodes

KW - rat brain

KW - Waste clearance

KW - [111In]-DTPA

U2 - 10.1177/0271678X231156982

DO - 10.1177/0271678X231156982

M3 - Journal article

C2 - 36809165

AN - SCOPUS:85148585708

VL - 43

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 7

ER -