High frame rate in vivo two-photon microscopy to quantify murine cerebrospinal fluid flow heterogeneity
- 1University of Minnesota
Abstract
Cerebrospinal fluid (CSF) flows through perivascular spaces (PVSs) surrounding brain vasculature, and impaired flow has been linked to neurodegenerative diseases such as Alzheimer's. However, the mechanisms driving CSF flow and its oscillatory dynamics remain poorly understood. Using high frame rate two-photon imaging (up to 113 Hz), we show that CSF flow is spatially heterogeneous and highly pulsatile, quantified using a regional CSF pulsatility index (PI). Reduced-order simulations with realistic domain length and Windkessel boundary conditions show that arterial pulsations generate peak CSF velocities but contribute negligibly to net transport. PI varies non-monotonically in space and substantially with downstream hydraulic resistance and compliance, indicating that CSF pulsatility is an emergent property of the hydraulic network rather than simply a consequence of local arterial wall motion. Measurements and simulations of the phase between arterial wall motion and CSF velocity further constrain proposed CSF driving mechanisms. Finally, we perform mouse-specific simulations to estimate average and peak wall shear stresses which support the potential role of pulsatile CSF flow in perivascular mechanotransduction. Together, these results establish CSF pulsatility as a measurable signature of network-scale CSF dynamics.
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BibTeX
@misc{gray2026high,
title = {{High frame rate in vivo two-photon microscopy to quantify murine cerebrospinal fluid flow heterogeneity}},
author = {C. Gray and K. Hu and D. H. Tse and K. Dieterle and S. Simpson and T. Ruhl and K. Duff and D. Kim and M. Mirzaee and A. Volker and T. S. Alturki and J. Tithof},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749497},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749497v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - High frame rate in vivo two-photon microscopy to quantify murine cerebrospinal fluid flow heterogeneity
AU - C. Gray
AU - K. Hu
AU - D. H. Tse
AU - K. Dieterle
AU - S. Simpson
AU - T. Ruhl
AU - K. Duff
AU - D. Kim
AU - M. Mirzaee
AU - A. Volker
AU - T. S. Alturki
AU - J. Tithof
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749497
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749497v1
AB - Cerebrospinal fluid (CSF) flows through perivascular spaces (PVSs) surrounding brain vasculature, and impaired flow has been linked to neurodegenerative diseases such as Alzheimer's. However, the mechanisms driving CSF flow and its oscillatory dynamics remain poorly understood. Using high frame rate two-photon imaging (up to 113 Hz), we show that CSF flow is spatially heterogeneous and highly pulsatile, quantified using a regional CSF pulsatility index (PI). Reduced-order simulations with realistic domain length and Windkessel boundary conditions show that arterial pulsations generate peak CSF velocities but contribute negligibly to net transport. PI varies non-monotonically in space and substantially with downstream hydraulic resistance and compliance, indicating that CSF pulsatility is an emergent property of the hydraulic network rather than simply a consequence of local arterial wall motion. Measurements and simulations of the phase between arterial wall motion and CSF velocity further constrain proposed CSF driving mechanisms. Finally, we perform mouse-specific simulations to estimate average and peak wall shear stresses which support the potential role of pulsatile CSF flow in perivascular mechanotransduction. Together, these results establish CSF pulsatility as a measurable signature of network-scale CSF dynamics.
ER -