Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease DOI
Rashi I. Mehta, Jeffrey Carpenter, Rupal I. Mehta

et al.

Radiology, Journal Year: 2021, Volume and Issue: 298(3), P. 654 - 662

Published: Jan. 5, 2021

Background Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-β plaque burden, improve memory performance, and facilitate delivery therapeutic agents brain. However, physiologic effects this procedure humans Alzheimer disease (AD) require further investigation. Purpose To assess imaging ultrasound–induced BBB opening hippocampus human participants early AD evaluate fluid flow patterns after by using serial contrast-enhanced MRI. Materials Methods Study recruited a Health Insurance Portability Accountability Act–compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate procedures that used 220-kHz transducer concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting entorhinal cortex between October 2018 May 2019. Posttreatment gadolinium-based enhancement were evaluated 3.0-T Results Three women (aged 61, 72, 73 years) consecutively enrolled successfully completed repeated cortex. Postprocedure was clearly identified within targeted brain volumes, indicating immediate spatially precise opening. Parenchymal resolved 24 hours all treatments, confirming closure. Transient perivenous consistently observed during acute Notably, reappeared perivenular regions This marker is consistent blood-meningeal permeability persisted for 24–48 before spontaneous resolution. No evidence intracranial hemorrhage or other adverse effect identified. Conclusion safely performed hippocampi without any effects. MRI reveals unique spatiotemporal pattern suggests immunologic healing response downstream from sites. © RSNA, 2021 Online supplemental material available article. See also editorial Klibanov issue.

Language: Английский

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain DOI
Katerina Deike‐Hofmann,

Julia Reuter,

Robert Haase

et al.

Investigative Radiology, Journal Year: 2018, Volume and Issue: 54(4), P. 229 - 237

Published: Nov. 22, 2018

The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies pathway through and out the central nervous system (CNS); malfunction is implicated in variety neurological disorders. In this exploratory study, we analyzed potential new imaging approach that coined delayed T2-weighted gadolinium-enhanced to visualize GS vivo.Heavily fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance was obtained before, 3 hours 24 after intravenous gadolinium-based contrast agent (GBCA) application 33 neurologically healthy patients 7 with an impaired blood-brain barrier (BBB) due cerebral metastases. Signal intensity (SI) determined various spaces, white matter hyperintensities were quantified by applying Fazekas scoring system.Delayed hT2w-FLAIR showed GBCA entry into CNS via choroid plexus ciliary body, drainage along perineural sheaths cranial nerves perivascular spaces penetrating cortical arteries. all sites, significant SI increase found for time points compared baseline. Although no difference between BBB, positive correlation post injection shown.Delayed can GS. Presence GBCAs within might be regarded as part natural excretion process should not mixed up gadolinium deposition. Rather, deep hyperintensities, sign vascular dementia, functioning demonstrated feasibility exploit diagnostic purposes.

Language: Английский

Citations

102
Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration DOI Creative Commons
Eric E. Smith, Geert Jan Biessels, François De Guio

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2019, Volume and Issue: 11(1), P. 191 - 204

Published: Feb. 25, 2019

Abstract Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus cerebral small vessel disease. Methods Surveys, teleconferences, an in‐person workshop were used identify gaps knowledge develop tools harmonizing analysis. Results A framework neuroimaging biomarker development was developed based validating repeatability reproducibility, biological principles, feasibility implementation. status current MRI biomarkers reviewed. website created at www.harness‐neuroimaging.org acquisition protocols, software database, rating scales case report forms, deidentified repository. Conclusions HARNESS initiative provides resources reduce variability measurement

Language: Английский

Citations

100
Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex DOI
Valentina Perosa, Jan Oltmer, Leon P. Munting

et al.

Acta Neuropathologica, Journal Year: 2021, Volume and Issue: 143(3), P. 331 - 348

Published: Dec. 20, 2021

Language: Английский

Citations

96
Altered perivascular fibroblast activity precedes ALS disease onset DOI
Anna Månberg, Nathan Skene,

Folkert Sanders

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(4), P. 640 - 646

Published: April 1, 2021

Language: Английский

Citations

90
Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease DOI
Rashi I. Mehta, Jeffrey Carpenter, Rupal I. Mehta

et al.

Radiology, Journal Year: 2021, Volume and Issue: 298(3), P. 654 - 662

Published: Jan. 5, 2021

Background Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-β plaque burden, improve memory performance, and facilitate delivery therapeutic agents brain. However, physiologic effects this procedure humans Alzheimer disease (AD) require further investigation. Purpose To assess imaging ultrasound–induced BBB opening hippocampus human participants early AD evaluate fluid flow patterns after by using serial contrast-enhanced MRI. Materials Methods Study recruited a Health Insurance Portability Accountability Act–compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate procedures that used 220-kHz transducer concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting entorhinal cortex between October 2018 May 2019. Posttreatment gadolinium-based enhancement were evaluated 3.0-T Results Three women (aged 61, 72, 73 years) consecutively enrolled successfully completed repeated cortex. Postprocedure was clearly identified within targeted brain volumes, indicating immediate spatially precise opening. Parenchymal resolved 24 hours all treatments, confirming closure. Transient perivenous consistently observed during acute Notably, reappeared perivenular regions This marker is consistent blood-meningeal permeability persisted for 24–48 before spontaneous resolution. No evidence intracranial hemorrhage or other adverse effect identified. Conclusion safely performed hippocampi without any effects. MRI reveals unique spatiotemporal pattern suggests immunologic healing response downstream from sites. © RSNA, 2021 Online supplemental material available article. See also editorial Klibanov issue.

Language: Английский

Citations

88