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Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

ABSTRACT: The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid ? clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

SUBMITTER: Iliff JJ

PROVIDER: S-EPMC3582150 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

Iliff Jeffrey J JJ Lee Hedok H Yu Mei M Feng Tian T Logan Jean J Nedergaard Maiken M Benveniste Helene H

The Journal of clinical investigation 20130222 3

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to a ...[more]

PMID: 23434588

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Project description:In the context of neurologic disorders, dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) MRI provide valuable insights into cerebral vascular function, integrity, and architecture. Even after two decades of use, these modalities continue to evolve as their biophysical and kinetic basis is better understood, with improvements in pulse sequences and accelerated imaging techniques and through application of more robust and automated data analysis strategies. Here, we systematically review each of these elements, with a focus on how their integration improves kinetic parameter accuracy and the development of new hemodynamic biomarkers that provide sub-voxel sensitivity (e.g., capillary transit time and flow heterogeneity). Regarding contrast mechanisms, we discuss the dipole-dipole interactions and susceptibility effects that give rise to simultaneous T1, T2 and T2∗ relaxation effects, including their quantification, influence on pulse sequence parameter optimization, and use in methods such as vessel size and vessel architectural imaging. The application of technologic advancements, such as parallel imaging, simultaneous multi-slice, undersampled k-space acquisitions, and sliding window strategies, enables improved spatial and/or temporal resolution of DSC and DCE acquisitions. Such acceleration techniques have also enabled the implementation of, clinically feasible, simultaneous multi-echo spin- and gradient echo acquisitions, providing more comprehensive and quantitative interrogation of T1, T2 and T2∗ changes. Characterizing these relaxation rate changes through different post-processing options allows for the quantification of hemodynamics and vascular permeability. The application of different biophysical models provides insight into traditional hemodynamic parameters (e.g., cerebral blood volume) and more advanced parameters (e.g., capillary transit time heterogeneity). We provide insight into the appropriate selection of biophysical models and the necessary post-processing steps to ensure reliable measurements while minimizing potential sources of error. We show representative examples of advanced DSC- and DCE-MRI methods applied to pathologic conditions affecting the cerebral microcirculation, including brain tumors, stroke, aging, and multiple sclerosis. The maturation and standardization of conventional DSC- and DCE-MRI techniques has enabled their increased integration into clinical practice and use in clinical trials, which has, in turn, spurred renewed interest in their technological and biophysical development, paving the way towards a more comprehensive assessment of cerebral hemodynamics.

Project description:Contrast-enhanced MRI (CE-MRI) is the most sensitive technique for breast cancer detection. Contrast-enhanced mammography (CEM) is emerging as a possible alternative to CE-MRI.PurposeTo evaluate the diagnostic performance of a low radiation dose contrast-enhanced mammography (L-CEM) in women with suspicious findings on conventional imaging compared to CE-MRI of the breast.Study typeProspective, single center.PopulationWomen with suspicious findings on mammography, tomosynthesis, or ultrasound, and no contraindications for L-CEM or CE-MRI. Eighty women were included.Field strength/sequence1.5 and 3T CE-MRI, standard protocol for breast, with dedicated coils, according to international guidelines. L-CEM was performed using a dedicated prototype.AssessmentThree, off-site, blinded readers evaluated the images according to the BI-RADS lexicon in a randomized order, each in two separate reading sessions. Histology served as a gold standard.Statistical testLesion detection rate, sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were calculated and compared with multivariate statistics.ResultsIncluded were 80 women (mean age, 54.3 years ±11.2 standard deviation) with 93 lesions (32 benign, 61 malignant). The detection rate was significantly higher with CE-MRI (92.5-94.6%; L-CEM 79.6-91.4%, P = 0.014). Sensitivity (L-CEM 65.6-90.2%; CE-MRI 83.6-93.4%, P = 0.086) and NPV (L-CEM 59.6-71.4%; CE-MRI 63.0-76.5%, P = 0.780) did not differ between the modalities. Specificity (L-CEM 46.9-96.9%; CE-MRI 37.5-53.1%, P = 0.001) and PPV (L-CEM 76.4-97.6%; CE-MRI 73.3-77.3%, P = 0.007) were significantly higher with L-CEM. Variations between readers were significant for sensitivity and NPV. The accuracy of L-CEM was as good as CE-MRI (75.3-76.3% vs. 72.0-75.3%, P = 0.514).Data conclusionL-CEM showed a high sensitivity and accuracy in women with suspicious findings on conventional imaging. Compared to CE-MRI, L-CEM has the potential to increase specificity and PPV. L-CEM might help to reduce false-positive biopsies while obtaining sensitivity comparable to that of CE-MRI LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:589-595.

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Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

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Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

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