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MRI of Whole Rat Brain Perivascular Network Reveals Role for Ventricles in Brain Waste Clearance

Journal Article · · Scientific Reports
 [1];  [2];  [2];  [2];  [3];  [2]
  1. Univ. of Florida, Gainesville, FL (United States); DOE/OSTI
  2. Univ. of Florida, Gainesville, FL (United States)
  3. Univ. of Florida, Gainesville, FL (United States); VA Medical Center, Gainesville, FL (United States)
+ Show Author Affiliations
Investigating the mechanisms by which metabolic wastes are cleared from nervous tissue is important for understanding natural function and the pathophysiology of several neurological disorders including Alzheimer’s disease. Recent evidence suggests clearance may be the function of annular spaces around cerebral blood vessels, called perivascular spaces (PVS), through which cerebrospinal fluid (CSF) is transported from the subarachnoid space into brain parenchyma to exchange with interstitial fluid (also known as the glymphatic system). In this work, an MRI-based methodology was developed to reconstruct the PVS network in whole rat brain to better elucidate both PVS uptake and clearance pathways. MR visible tracer (Gd-albumin) was infused in vivo into the CSF-filled lateral ventricle followed by ex vivo high-resolution MR imaging at 17.6 T with an image voxel volume two orders of magnitude smaller than previously reported. Imaged tracer distribution patterns were reconstructed to obtain a more complete brain PVS network. Several PVS connections were repeatedly highlighted across different animals, and new PVS connections between ventricles and different parts of the brain parenchyma were revealed suggesting a possible role for the ventricles as a source or sink for solutes in the brain. In the future, this methodology may be applied to understand changes in the PVS network with disease.
Research Organization:
Univ. of Florida, Gainesville, FL (United States). National High Magnetic Field Lab. (NHMFL)
Sponsoring Organization:
USDOE; National Science Foundation (NSF); National Institutes of Health (NIH)
OSTI ID:
1624474
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 9; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (53)

k-t BLAST andk-t SENSE: Dynamic MRI with high frame rate exploiting spatiotemporal correlations journal October 2003
Visualization of neural tissue water compartments using biexponential diffusion tensor MRI journal January 2001
Magnetic field and tissue dependencies of human brain longitudinal1H2O relaxation in vivo journal January 2007
Radio frequency coil technology for small-animal MRI journal January 2007
Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images journal October 2002
Diurnal fluctuation in levels of histamine metabolites in cerebrospinal fluid of rhesus monkey journal March 1989
The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? journal February 2018
Computational Model of Interstitial Transport in the Spinal Cord using Diffusion Tensor Imaging journal July 2006
The Glymphatic System: A Beginner’s Guide journal May 2015
A voxelized model of direct infusion into the corpus callosum and hippocampus of the rat brain: model development and parameter analysis journal December 2009
Evidence for a ‘Paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space journal February 1985
Distribution of extracellular tracers in perivascular spaces of the rat brain journal April 1991
Diffusion of albumins in rat cortical slices and relevance to volume transmission journal December 1996
Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease journal September 2016
Fsl journal August 2012
Magnetic resonance microscopy of human and porcine neurons and cellular processes journal April 2012
Flow of cerebral interstitial fluid as indicated by the removal of extracellular markers from rat caudate nucleus journal January 1977
A global optimisation method for robust affine registration of brain images journal June 2001
A new transgene reporter for in vivo magnetic resonance imaging journal March 2005
An artery-specific fluorescent dye for studying neurovascular coupling journal January 2012
CLARITY for mapping the nervous system journal June 2013
Glymphatic solute transport does not require bulk flow journal December 2016
Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes journal October 1997
A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules journal June 2015
Comparison of Magnetic Properties of MRI Contrast Media Solutions at Different Magnetic Field Strengths journal January 2005
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid   journal August 2012
The Binding of T-1824 and Structurally Related Diazo dyes by the Plasma Proteins journal April 1943
Bathing the brain journal February 2013
Impairment of the glymphatic system after diabetes journal July 2016
Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer journal May 2013
Pulsatile flow drivers in brain parenchyma and perivascular spaces: a resistance network model study journal July 2018
Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities journal January 2023
Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System journal January 2015
Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: Implications for gene and drug therapy journal March 2014
Aldehyde fixative solutions alter the water relaxation and diffusion properties of nervous tissue: Aldehyde Fixation Alters Tissue MRI Properties journal April 2009
MRI reporter genes: applications for imaging of cell survival, proliferation, migration and differentiation journal December 2012
Diurnal fluctuation in levels of histamine metabolites in cerebrospinal fluid of rhesus monkey journal March 1989
Diffusion of albumins in rat cortical slices and relevance to volume transmission journal December 1996
Flow of cerebral interstitial fluid as indicated by the removal of extracellular markers from rat caudate nucleus journal January 1977
A global optimisation method for robust affine registration of brain images journal June 2001
User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability journal July 2006
ScaleS: an optical clearing palette for biological imaging journal September 2015
Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow journal August 2017
A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis journal January 2000
Albumin Labeled with Gd-DTPA journal August 1987
Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery journal December 2017
Brain-wide pathway for waste clearance captured by contrast-enhanced MRI journal February 2013
Brain-wide glymphatic enhancement and clearance in humans assessed with MRI journal July 2018
Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain journal September 2016
Impairment of the glymphatic system after diabetes journal July 2016
Colloidal gold, a useful marker for transmission and scanning electron microscopy. journal April 1977
Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System journal January 2015
Aquaporin-4-dependent glymphatic solute transport in the rodent brain journal December 2018

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Figures / Tables (8)

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