scholarly journals Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus

2019 ◽  
Vol 40 (9) ◽  
pp. 1849-1858 ◽  
Author(s):  
Per Kristian Eide ◽  
Lars Magnus Valnes ◽  
Are Hugo Pripp ◽  
Kent-Andre Mardal ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Choroid Plexus ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Resonance Imaging ◽  
Lateral Ventricles

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.

scholarly journals Magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics  in idiopathic normal pressure hydrocephalus

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Per Kristian Eide ◽  
Are H Pripp ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Imaging Biomarkers ◽  
Resonance Imaging ◽  
Intracranial Compliance ◽  
The Brain

Abstract Disturbed clearance of toxic metabolites from the brain via cerebrospinal fluid is emerging as an important mechanism behind dementia and neurodegeneration. To this end, magnetic resonance imaging work-up of dementia diseases is largely focused on anatomical derangements of the brain. This study explores magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in patients with the dementia subtype idiopathic normal pressure hydrocephalus and a cohort of reference subjects. All study participants underwent multi-phase magnetic resonance imaging up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml, 1 mmol/ml), serving as cerebrospinal fluid tracer. Imaging biomarkers of cerebrospinal fluid tracer dynamics (i.e. ventricular reflux grades 0–4 and clearance) were compared with anatomical magnetic resonance imaging biomarkers of cerebrospinal fluid space anatomy (Evans’ index, callosal angle and disproportional enlargement of subarachnoid spaces hydrocephalus) and neurodegeneration (Schelten’s medial temporal atrophy scores, Fazeka’s scores and entorhinal cortex thickness). The imaging scores were also related to a pulsatile intracranial pressure score indicative of intracranial compliance. In shunt-responsive idiopathic normal pressure hydrocephalus, the imaging biomarkers demonstrated significantly altered cerebrospinal fluid tracer dynamics (ventricular reflux grades 3–4 and reduced clearance of tracer), deranged cerebrospinal fluid space anatomy and pronounced neurodegeneration. The altered MRI biomarkers were accompanied by pressure indices of impaired intracranial compliance. In conclusion, we present novel magnetic resonance imaging biomarkers characterizing idiopathic normal pressure hydrocephalus pathophysiology, namely measures of cerebrospinal fluid molecular redistribution and clearance, which add information to traditional imaging scores of cerebrospinal fluid space anatomy and neurodegeneration.

scholarly journals Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: A glymphatic magnetic resonance imaging study

2018 ◽  
Vol 39 (7) ◽  
pp. 1355-1368 ◽  
Author(s):  
Per K Eide ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Entorhinal Cortex ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Toxic Waste ◽  
Resonance Imaging ◽  
Csf Leaks

The glymphatic system plays a key role for clearance of waste solutes from the rodent brain. We recently found evidence of glymphatic circulation in the human brain when using magnetic resonance imaging (MRI) contrast agent as cerebrospinal fluid (CSF) tracer in conjunction with multiple MRI acquisitions (gMRI). The present study explored the hypothesis that reduced glymphatic clearance in entorhinal cortex (ERC) may be instrumental in idiopathic normal pressure hydrocephalus (iNPH) dementia. gMRI acquisitions were obtained over a 24–48 h time span in cognitively affected iNPH patients and non-cognitively affected patients with suspected CSF leaks. The CSF tracer enrichment was determined as changes in normalized MRI T1 signal units. The study included 30 patients with iNPH and 8 individuals with suspected CSF leaks (i.e. reference individuals). Compared to reference individuals, iNPH patients presented with higher medial temporal lobe atrophy score and Evan's index and inferior ERC thickness. We found delayed clearance of the intrathecal CSF tracer gadobutrol from CSF, the ERC and adjacent white matter, suggesting impaired glymphatic circulation. Reduced clearance and accumulation of toxic waste product such as amyloid-β may be a mechanism behind dementia in iNPH. Glymphatic MRI (gMRI) may become a tool for assessment of early dementia.

Sign in / Sign up

Export Citation Format

Share Document