Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI

Harrison, Ian F.; Siow, Bernard; Akilo, Aisha B; Evans, Phoebe; Ismail, Ozama; Ohene, Yolanda; Nahavandi, Payam; Thomas, David L.; Lythgoe, Mark F.; Wells, Jack A.

doi:10.7554/elife.34028

Cited by 118 publications

(111 citation statements)

References 41 publications

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“…It has been suggested that glymphatic dysfunction represents a fundamental constituent of cSVD . Although it has previously been shown in the rat brain that diffusion MRI has the potential for the assessment of perivascular fluid motion in relation to the glymphatic system, whether the current clinical application of NNLS‐based IVIM can accurately detect glymphatic failure remains to be investigated. For this, future studies should combine these measures with assessments of cardiac pulsatility (eg, pulsatility of small perforating lenticulostriatal arteries) and aquaporin‐4 dependent fluid movement .…”

Section: Discussionmentioning

confidence: 99%

Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease

Wong

Backes

Drenthen

et al. 2019

Magnetic Resonance Imaging

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Background Cerebral intravoxel incoherent motion (IVIM) imaging assumes two components. However, more compartments are likely present in pathologic tissue. We hypothesized that spectral analysis using a nonnegative least‐squares (NNLS) approach can detect an additional, intermediate diffusion component, distinct from the parenchymal and microvascular components, in lesion‐prone regions. Purpose To investigate the presence of this intermediate diffusion component and its relation with cerebral small vessel disease (cSVD)‐related lesions. Study Type Prospective cross‐sectional study. Population Patients with cSVD (n = 69, median age 69.8) and controls (n = 39, median age 68.9). Field Strength/Sequence Whole‐brain inversion recovery IVIM acquisition at 3.0T. Assessment Enlarged perivascular spaces (PVS) were rated by three raters. White matter hyperintensities (WMH) were identified on a fluid attenuated inversion recovery (FLAIR) image using a semiautomated algorithm. Statistical Tests Relations between IVIM measures and cSVD‐related lesions were studied using the Spearman's rank order correlation. Results NNLS yielded diffusion spectra from which the intermediate volume fraction fint was apparent between parenchymal diffusion and microvasular pseudodiffusion. WMH volume and the extent of MRI‐visible enlarged PVS in the basal ganglia (BG) and centrum semiovale (CSO) were correlated with fint in the WMHs, BG, and CSO, respectively. fint was 4.2 ± 1.7%, 7.0 ± 4.1% and 13.6 ± 7.7% in BG and 3.9 ± 1.3%, 4.4 ± 1.4% and 4.5 ± 1.2% in CSO for the groups with low, moderate, and high number of enlarged PVS, respectively, and increased with the extent of enlarged PVS (BG: r = 0.49, P < 0.01; CSO: r = 0.23, P = 0.02). fint in the WMHs was 27.1 ± 13.1%, and increased with the WMH volume (r = 0.57, P < 0.01). Data Conclusion We revealed the presence of an intermediate diffusion component in lesion‐prone regions of cSVD and demonstrated its relation with enlarged PVS and WMHs. In tissue with these lesions, tissue degeneration or perivascular edema can lead to more freely diffusing interstitial fluid contributing to fint. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1170–1180.

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Section: Discussionmentioning

confidence: 99%

Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease

Wong

Backes

Drenthen

et al. 2019

Magnetic Resonance Imaging

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“…Further confirmation of this flow pattern in a non‐invasive manner was provided by the work of Harrison et al. (). Using novel magnetic resonance imaging sequences, these authors showed that CSF flows along the middle cerebral artery in rats.…”

Section: The Paravascular Space and Direction Of Flowmentioning

confidence: 57%

“…Using microsphere tracking, recent work from our group confirmed that at the brain surface, CSF flows along arteries in the direction of blood flow in a pulsatile manner (Bedussi, Almasian, de Vos, VanBavel, & Bakker, 2018). Further confirmation of this flow pattern in a noninvasive manner was provided by the work of Harrison et al (2018).…”

Section: The Paravascular Space and Direction Of Flowmentioning

confidence: 71%

Paravascular spaces: entry to or exit from the brain?

Bakker

Naessens

VanBavel

2019

Experimental Physiology

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New Findings What is the topic of this review? In this symposium report, we review the glymphatic clearance from the brain. What advances does it highlight? Evaluation of the evidence indicates that cerebrospinal fluid flows along paravascular spaces at the surface of the brain. However, bulk flow along penetrating arteries into the brain, followed by exit along veins, requires further confirmation. Clearance from the brain, based on mixing, might provide an alternative explanation for experimental findings. Abstract The interstitial fluid of the brain provides the environment for proper neuronal function. Maintenance of the volume and composition of interstitial fluid requires regulation of the influx and removal of water, ions, nutritive and waste products. The recently described glymphatic pathway might contribute to some of these functions. It is proposed that cerebrospinal fluid enters the brain via paravascular spaces along arteries, mixes with interstitial fluid, and leaves the brain via paravascular spaces along veins. In this symposium report, we review the glymphatic concept, its concerns, and alternative views on interstitial fluid–cerebrospinal fluid exchange.

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“…Therefore, alternative methods are needed to investigate the glymphatic system non-invasively, especially in the human brain. Fluid-dynamics driven and BOLD fast MRI have the potential to evaluate CSF pulsations in the ventricles and hemodynamics [11,20,21], while IVIM and diffusion MRI have been shown as promising methods for the evaluation of the ISF [7,22–24].…”

Section: Introductionmentioning

confidence: 99%

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

Debacker¹,

Djemaï²,

Tsurugizawa³

et al. 2020

Preprint

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21The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its 22 dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key 23 component of the GS and brain tissue water circulation is the astrocyte which is regulated by 24 acquaporin4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we 25 investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model 26 through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a 27 significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase 28 of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline 29 injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo 30 and non-invasively. 31

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Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI

Cited by 118 publications

References 41 publications

Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease

Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease

Paravascular spaces: entry to or exit from the brain?

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

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