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

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...

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Published inBrain communications Vol. 2; no. 2; p. fcaa187
Main Authors Eide, Per Kristian, Pripp, Are H, Ringstad, Geir
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.01.2020
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Abstract 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. Disturbed clearance of toxic metabolites from brain via cerebrospinal fluid is emerging as an important mechanism behind dementia. This study presents MRI biomarkers characterizing cerebrospinal fluid molecular redistribution and clearance and degree of neurodegeneration in human brain of patients with a dementia subtype. Graphical Abstract Graphical Abstract
AbstractList 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. Disturbed clearance of toxic metabolites from brain via cerebrospinal fluid is emerging as an important mechanism behind dementia. This study presents MRI biomarkers characterizing cerebrospinal fluid molecular redistribution and clearance and degree of neurodegeneration in human brain of patients with a dementia subtype. Graphical Abstract
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.
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.
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. Disturbed clearance of toxic metabolites from brain via cerebrospinal fluid is emerging as an important mechanism behind dementia. This study presents MRI biomarkers characterizing cerebrospinal fluid molecular redistribution and clearance and degree of neurodegeneration in human brain of patients with a dementia subtype. Graphical Abstract Graphical 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.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.
Author Eide, Per Kristian
Pripp, Are H
Ringstad, Geir
AuthorAffiliation 3 Oslo Centre of Biostatistics and Epidemiology, Oslo University Hospital , Oslo, Norway
1 Department of Neurosurgery, Oslo University Hospital-Rikshospitalet , Oslo, Norway
2 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo, Norway
4 Department of Radiology, Oslo University Hospital- Rikshospitalet , Oslo, Norway
AuthorAffiliation_xml – name: 2 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo, Norway
– name: 1 Department of Neurosurgery, Oslo University Hospital-Rikshospitalet , Oslo, Norway
– name: 4 Department of Radiology, Oslo University Hospital- Rikshospitalet , Oslo, Norway
– name: 3 Oslo Centre of Biostatistics and Epidemiology, Oslo University Hospital , Oslo, Norway
Author_xml – sequence: 1
  givenname: Per Kristian
  orcidid: 0000-0001-6881-9280
  surname: Eide
  fullname: Eide, Per Kristian
  email: p.k.eide@medisin.uio.no
  organization: Department of Neurosurgery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
– sequence: 2
  givenname: Are H
  surname: Pripp
  fullname: Pripp, Are H
  organization: Oslo Centre of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
– sequence: 3
  givenname: Geir
  surname: Ringstad
  fullname: Ringstad, Geir
  organization: Department of Radiology, Oslo University Hospital- Rikshospitalet, Oslo, Norway
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33381757$$D View this record in MEDLINE/PubMed
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Issue 2
Keywords idiopathic normal pressure hydrocephalus
glymphatic system
MRI biomarkers
ICP
cerebrospinal fluid
Language English
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Snippet Abstract Disturbed clearance of toxic metabolites from the brain via cerebrospinal fluid is emerging as an important mechanism behind dementia and...
Disturbed clearance of toxic metabolites from the brain via cerebrospinal fluid is emerging as an important mechanism behind dementia and neurodegeneration. To...
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Title Magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in idiopathic normal pressure hydrocephalus
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http://hdl.handle.net/10852/85572
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