Perivascular cerebrospinal fluid inflow matches interstitial fluid efflux in anesthetized rat brains

Published: 8 April 2025| Version 1 | DOI: 10.17632/78rvmj2wh8.1
Contributor:
Kristian Mortensen

Description

This dataset contains all MRI from the paper: "Perivascular cerebrospinal fluid inflow matches interstitial fluid efflux in anesthetized rat brains". It consists of dynamic contrast-enhanced MRI after infusion of tracers in the cerebrospinal fluid (CSF) in the cisterna magna. The paper details the quantification of CSF inflow into brain tissue based on these data and validation data. data/Gd-DTPA contains data from the main experiment: T2-imaging to measure pial perivascular space cross-sectional area and dynamic contrast-enhanced MRI after infusion of Gd-DTPA in CSF to track CSF flow around and into the brain. data/GadospinP contains data from a validation experiment with a larger tracer molecule to validate that the observed flow velocity was not affected by diffusion effects of infusion artefacts. data/high_res_T2 contains data from a validation experiment to test how the imaging sequence affects the measured pial perivascular space cross-sectional area. data/template contains an anatomical template described here: https://doi.org/10.1016/j.jconrel.2023.01.054. The file 'input_sources.nii.gz' contains the template-space definition of the subarachnoid-space territory of the middle cerebral arteries used in the calculation of the CSF perfusion territory of the middle cerebral artery (Fig. 3 in the paper). code/python contains python scripts to produce quantitative DCE-MRI time series, i.e. 4D tracer concentration images. code/matlab contains Matlab scripts implementing the calculations necessary to produce the results described in the paper. Abstract: Waste solutes are cleared from the brain via outflow of interstitial fluid (ISF). Blood-brain-barrier water secretion and inflow of cerebrospinal fluid (CSF) via perivascular channels have been suggested as potential fluid sources to replace outflowing ISF. To assess the role of CSF inflow in brain clearance, we measured both CSF inflow and ISF outflow in ketamine/dexmedetomidine anesthetized rats. We used magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) to track tracer flows after infusion in CSF or ISF. CSF inflow was estimated at 0.5-0.7 µl·g-1·min-1 using either direct observation of perivascular flow or compartment modelling. ISF outflow was estimated at 0.47±0.05 µl·g-1·min-1 after intraparenchymal infusion. Our observations indicate that under the anesthetic condition examined, inflowing CSF is sufficient to replace outflowing ISF, that perivascular flow and CSF inflow to interstitium are dominated by convection, and that diffusion and convection both contribute to tracer transport within the brain parenchyma.

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MRI experiments were carried out on a 9.4T magnet Bruker BioSpec 94/30 USR) interfaced to a Bruker Avance III console and controlled by Paravision software (Bruker) v5. Imaging was carried out using an 86 mm volume RF-transmit coil and a 4-channel phased array RF receiver coil (Bruker). Rats (Sprague-Dawley ,175-400 g) were anesthetized with a mixture of ketamine (100 mg/kg, Ketaminol® Vet, MSD) and dexmedetomidine (0.5 mg/kg, Dexdomitor, Orion Pharma, Espoo, Finland) administered subcutaneously (2 ml/kg) and placed prone in the magnet with the teeth fixed in a bite bar. The surface receiver coil was centered over the cerebrum. Core temperature and respiration (in the case of non-ventilated experiments) were monitored using an MRI-compatible monitoring system (SA Instruments) for the duration of the experiment and heated waterbed was used to maintain the core temperature at 36.5-37.5°C. Gd-DTPA experiments consisted of: - Anatomical T2-weighted Rapid Acquisition with Relaxation Enhancement (RARE) images (echo time (TE): 36 ms, repetition time (TR): 16 s, RARE factor: 8, matrix: 330x384, , field of view (FOV): 30x35 mm, 128 slices, slice thickness: 0.312 mm; slice overlap: 0.156 mm, 2 frames). - Contrast infusion in Cisterna Magna (Gd-DTPA, 0.5 kDa, 12.5mM, 40µl, 2µl·min-1) - Quantitative DCE-MRI (https://doi.org/10.1002/mrm.26779): a double angle-experiment to measure RF transmission inhomogeneity using the 2D RARE sequence (TE: 22 ms, TR: 10 s, RARE factor: 4, 50 slices, matrix 128x128, FOV: 30x32mm, slice thickness: 0.4 mm; slice gap: 0.2 mm; FA: 70° and 140°), followed by variable flip angle SPGR to measure a baseline T1-map (TE: 4 ms, TR: 15 ms, matrix: 128x128x128, FOV: 30x32x30, flip angle (FA): 2, 5, 10, 15, 20, 30, frame rate: 4m5s min). DCE-MRI consisted of 3D SPGR images map (same parameters except FA: 15, frame rate: 4m5s, 3 baseline frames, 42 post-infusion frames). GadospinP experiments consisted of: - DCE-MRI: 3D SPGR images map (TE: 2.2 ms, TR: 11.6 ms, matrix: 280x75x340, FOV: 28x15x34 mm, FA: 15, frame rate: 2m30s min, 3 baseline frames, 24 post-infusion frames). High-resolution T2 experiments consisted of: - Anatomical T2-images: RARE (TE: 24.1ms, TR: 16s, Echo spacing: 8.033, RARE factor: 8, matrix: 375x250FOV): 30x20mm, 128 slices, slice thickness 220um, 110 um overlap, 8 repetitions, frame rate 6m8s). Creation of the high-resolution T2-template and tissue atlas was described in another paper: https://doi.org/10.1016/j.jconrel.2023.01.054

Categories

Magnetic Resonance Imaging, Cerebrospinal Fluid, Clearance Mechanism, Dynamic Contrast-Enhanced Imaging

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