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

Björn Sigurdsson; Natalie L. Hauglund; Tuomas O. Lilius; Frida L.H. Mogensen; Kristian N. Mortensen; Natalie Beschorner; Laura Klinger; Simone L. Bærentzen; Marko P. Rosenholm; Vladimir Shalgunov; Matthias Herth; Yuki Mori; Maiken Nedergaard

doi:10.1177/0271678X231156982

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

Björn Sigurdsson, Natalie L. Hauglund, Tuomas O. Lilius, Frida L.H. Mogensen, Kristian N. Mortensen, Natalie Beschorner, Laura Klinger, Simone L. Bærentzen, Marko P. Rosenholm, Vladimir Shalgunov, Matthias Herth, Yuki Mori, Maiken Nedergaard^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

10 Citations (Scopus)

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.

Original language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	43
Issue	7
Pages (from-to)	1153 - 1165
Number of pages	13
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678X231156982
Publication status	Published - Jul 2023

Keywords

cerebrospinal fluid dynamics
lymph nodes
rat brain
Waste clearance
[111In]-DTPA
Animals
Glymphatic System
Tomography, Emission-Computed, Single-Photon
Rats
Single Photon Emission Computed Tomography Computed Tomography
Magnetic Resonance Imaging/methods
Brain/blood supply

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10.1177/0271678X231156982

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Sigurdsson, B., Hauglund, N. L., Lilius, T. O., Mogensen, F. L. H., Mortensen, K. N., Beschorner, N., Klinger, L., Bærentzen, S. L., Rosenholm, M. P., Shalgunov, V., Herth, M., Mori, Y., & Nedergaard, M. (2023). A SPECT-based method for dynamic imaging of the glymphatic system in rats. Journal of Cerebral Blood Flow and Metabolism, 43(7), 1153 - 1165. https://doi.org/10.1177/0271678X231156982

@article{7acafed698004cffb8163956c654c912,

title = "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.",

keywords = "cerebrospinal fluid dynamics, lymph nodes, rat brain, Waste clearance, [111In]-DTPA, Animals, Glymphatic System, Tomography, Emission-Computed, Single-Photon, Rats, Single Photon Emission Computed Tomography Computed Tomography, Magnetic Resonance Imaging/methods, Brain/blood supply",

author = "Bj{\"o}rn Sigurdsson and Hauglund, {Natalie L.} and Lilius, {Tuomas O.} and Mogensen, {Frida L.H.} and Mortensen, {Kristian N.} and Natalie Beschorner and Laura Klinger and B{\ae}rentzen, {Simone L.} and Rosenholm, {Marko P.} and Vladimir Shalgunov and Matthias Herth and Yuki Mori and Maiken Nedergaard",

note = "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 Publisher Copyright: {\textcopyright} The Author(s) 2023.",

year = "2023",

month = jul,

doi = "10.1177/0271678X231156982",

language = "English",

volume = "43",

pages = "1153 -- 1165",

journal = "Journal of Cerebral Blood Flow and Metabolism",

issn = "0271-678X",

publisher = "SAGE Publications Ltd",

number = "7",

}

Sigurdsson, B, Hauglund, NL, Lilius, TO, Mogensen, FLH, Mortensen, KN, Beschorner, N, Klinger, L, Bærentzen, SL, Rosenholm, MP, Shalgunov, V, Herth, M, Mori, Y & Nedergaard, M 2023, 'A SPECT-based method for dynamic imaging of the glymphatic system in rats', Journal of Cerebral Blood Flow and Metabolism, vol. 43, no. 7, pp. 1153 - 1165. https://doi.org/10.1177/0271678X231156982

A SPECT-based method for dynamic imaging of the glymphatic system in rats. / Sigurdsson, Björn; Hauglund, Natalie L.; Lilius, Tuomas O. et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 43, No. 7, 07.2023, p. 1153 - 1165.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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 Publisher Copyright: © The Author(s) 2023.

PY - 2023/7

Y1 - 2023/7

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

KW - Animals

KW - Glymphatic System

KW - Tomography, Emission-Computed, Single-Photon

KW - Rats

KW - Single Photon Emission Computed Tomography Computed Tomography

KW - Magnetic Resonance Imaging/methods

KW - Brain/blood supply

UR - http://www.scopus.com/inward/record.url?scp=85148585708&partnerID=8YFLogxK

U2 - 10.1177/0271678X231156982

DO - 10.1177/0271678X231156982

M3 - Journal article

C2 - 36809165

AN - SCOPUS:85148585708

SN - 0271-678X

VL - 43

SP - 1153

EP - 1165

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 7

ER -

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

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Keywords

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