Publisher Correction: Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System

Koundal, Sunil; Elkin, Rena; Nadeem, Saad; Xue, Yuechuan; Constantinou, Stefan; Sanggaard, Simon; Liu, Xiaodan; Monte, Brittany; Xu, Feng; Nostrand, William Van; Lee, Hedok; Wardlaw, Joanna M.; Benveniste, Helene; Tannenbaum, Allen

doi:10.1038/s41598-020-60586-2

Cited by 9 publications

(2 citation statements)

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“…However, some studies 35–37 have questioned the role of advection and contended that diffusion plays the most important role in the transport of neurofluids 38–44 . One recent study 45,46 used mathematic modeling to suggest that both diffusion and advection are involved in fluid transport in the parenchyma. However, a review of such studies 47 concluded that there is a consensus that suggests diffusion is most likely the primary agent that drives fluid transport in the interstitial space.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the DTI‐ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia

Steward

Venkatraman

Lui

et al. 2021

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI‐ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS All 36 participants imaged on a Siemens 3.0T Tim Trio. Single‐SE diffusion weighted Echo‐planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI‐ALPS parameter was calculated in these regions and correlated with cognitive status, Mini‐Mental State Examination (MMSE), and ADASCog11 measures. RESULTS Significant correlations were found between DTI‐ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI‐ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION Further work is needed to determine the utility of DTI‐ALPS index in larger elderly cohorts and whether it measures glymphatic activity.

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Section: Discussionmentioning

confidence: 99%

Assessment of the DTI‐ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia

Steward

Venkatraman

Lui

et al. 2021

Journal of Neuroimaging

View full text Add to dashboard Cite

show abstract

“…Typically, cluster analysis is performed on time-series signal data to show the speed of contrast agent uptake in different brain regions or the general direction of contrast agent movement (17,31,38). Optimal mass transport (OMT) modelling has emerged as an excellent tool for visualizing movement of intrathecal contrast agents through the brain (39). However, these semi-quantitative techniques do not permit the determination of the fundamental parameters characterizing molecular transport that are independent of experimental procedures and allow direct comparison with known diffusion rates.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Analysis of Macroscopic Solute Transport in the Murine Brain

Ray

Pike

Simon

et al. 2021

Preprint

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Background: Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE) MRI offers a whole-brain view of transport and the potential for quantitative analysis to determine fundamental transport parameters. However, few DCE-MRI studies have utilized this potential, instead reporting parameters with arbitrary units disconnected from fundamental transport processes. Methods: In this work, DCE-MRI experimental data is combined with subject-specific finite-element models to quantify transport parameters in different anatomical regions across the whole mouse brain. Effective diffusivity ( ), a transport parameter combining all mechanisms of transport, is determined for each region by minimizing the root mean square error between simulations and data. The resulting sets are compared to apparent diffusivity ( ) to draw conclusions about dominant transport mechanisms in each region. Results: In the perivascular regions of major arteries, was over 10,000 times greater than . In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, was 10-25 times greater than .Conclusions: The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 10,000) and significant to large molecules (>1 kDa) in the combined interstitial space and perivascular space of smaller arteries (not resolved by DCE-MRI). Importantly, this work supports periarterial convection along penetrating and smaller arteries.

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Brain Glymphatic/Lymphatic Imaging by MRI and PET

Lee

Suh

Sarker

et al. 2020

Nucl Med Mol Imaging

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Since glymphatic was proposed and meningeal lymphatic was discovered, MRI and even PET were introduced to investigate brain parenchymal interstitial fluid (ISF), cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previous findings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodents were reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRI in rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrast to rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSF-lymphatic efflux. In mice, ISF-CSF exchange was examined thoroughly using an intra-cistern injection of fluorescent tracers during sleep, aging, and neurodegeneration yielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over the dorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymph nodes and systemic circulation is also well-delineated especially in humans onintrathecal contrast MRI. Sleep-or anesthesia-related changes of glymphatic-lymphatic flow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humans should be interpreted based on human anatomy and physiology, different in some aspects, using MRI recently. Based on the summary in this review, we propose non-invasive and longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.

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Publisher Correction: Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 9 publications

References 0 publications

Assessment of the DTI‐ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia

Assessment of the DTI‐ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia

Quantitative Analysis of Macroscopic Solute Transport in the Murine Brain

Brain Glymphatic/Lymphatic Imaging by MRI and PET

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