Glymphatic Pathway in Brain Imaging
Study Details
Study Description
Brief Summary
To investigate the pathways of Gadolinium-based contrast agent (GBCA) in different brain compartments and evaluate correlations of GBCA enhancement with specific diseases.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
To investigate the contrast enhancement in different brain compartments. Until recently, it had been assumed that Gadolinium-based contrast agents do not cross the blood-brain barrier, but delayed imaging revealed signal increase in a number of compartments in the CSF (the perilymph of the inner ear, the internal auditory canal, the Meckel's cave, the suprasellar cistern, the ambient cistern and anterior eye compartment). These findings suggested, that Gadolinium-based contrast agents (GBCA) penetrate into the CSF through the choroid plexus and the aqueous chamber of the eye. MRI has provided the evidence of presence of meningeal lymphatic vessels in human and non-human primates for central nervous system waste clearance. It has been demonstrated that heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) MRI detects even very low concentrations of GBCA in the CSF.
The aim of our study is to find specific enhancement patterns in various cerebral compartments in correlation with specific diseases and procedures such as radiation, surgery and drug application in delayed gadolinium imaging. Only patients with a clinical indication for GBCA will be included in this prospective study. Before enrollment, each patient will have provided written informed consent of participation and publication prior to inclusion to the observational study. The scan will be performed as baseline before intravenous contrast administration of a single dose of gadoteric acid 20 minutes and 120 minutes after contrast administration. Whole-brain image stacks will be analyzed on patient basis. Regions of interest for signal intensity measurements will be drawn in various cerebral fluid spaces, the size of the region of interest will depend on the target structure. The following structures should be measured: lateral and central aqueous chamber and vitreous body of the eye, distal optic nerve sheath, Meckel's cave, lateral ventricles and basal cisterns.
Data will be expressed as mean values +/- one-fold standard deviation (SD). The normality of data distribution will be assessed using Levene's test. Data showing a Gaussian distribution will be evaluated by an analysis of variances (ANOVA) with a post-hoc analysis. Estimated sample size is around 30 patients in the control and the experimental group. Cases with missing or unavailable data will be excluded.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| experimental patients with a condition |
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| control patients without condition |
Outcome Measures
Primary Outcome Measures
- Change of Signal-Intensity (SI)-Measurements with ROI in 3 specific MRI Scans [Baseline (nativ scan), 20 minutes and 120 minutes after contrast media application]
Regions of interest for signal intensity measurements will be drawn in various cerebral fluid spaces, the size of the region of interest will depend on the target structure. Following structures will be measured: lateral and central aqueous chamber and vitreous body of the eye, distal optic nerve sheath, Meckel's cave, lateral ventricles and basal cisterns.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Only patients with a clinical indication for GBCA
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Written informed consent
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No allergies to GBCA
Exclusion Criteria:
- Contraindications for MRI
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Radiology and Nuclear Medicine | Nuremberg | Bavaria | Germany | 90419 |
Sponsors and Collaborators
- Paracelsus Medical University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6. pii: e29738. doi: 10.7554/eLife.29738.
- Bedussi B, Almasian M, de Vos J, VanBavel E, Bakker EN. Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow. J Cereb Blood Flow Metab. 2018 Apr;38(4):719-726. doi: 10.1177/0271678X17737984. Epub 2017 Oct 17. Erratum in: J Cereb Blood Flow Metab. 2018 Apr;38(4):746.
- Deike-Hofmann K, Reuter J, Haase R, Paech D, Gnirs R, Bickelhaupt S, Forsting M, Heußel CP, Schlemmer HP, Radbruch A. Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted. Invest Radiol. 2019 Apr;54(4):229-237. doi: 10.1097/RLI.0000000000000533.
- Dobson H, Sharp MM, Cumpsty R, Criswell TP, Wellman T, Finucane C, Sullivan JM, Weller RO, Verma A, Carare RO. The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain. Clin Sci (Lond). 2017 Nov 13;131(22):2745-2752. doi: 10.1042/CS20171265. Print 2017 Nov 15.
- Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012 Aug 15;4(147):147ra111. doi: 10.1126/scitranslmed.3003748.
- Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y, Deane R, Nedergaard M. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci. 2013 Nov 13;33(46):18190-9. doi: 10.1523/JNEUROSCI.1592-13.2013.
- Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA. 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. Brain Res. 1985 Feb 4;326(1):47-63.
- Smith AJ, Yao X, Dix JA, Jin BJ, Verkman AS. Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife. 2017 Aug 21;6. pii: e27679. doi: 10.7554/eLife.27679.
- Taoka T, Naganawa S. Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain. Magn Reson Med Sci. 2018 Apr 10;17(2):111-119. doi: 10.2463/mrms.rev.2017-0116. Epub 2018 Jan 25.
- GP_2021_KNN