Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Jeffrey B. Ware; Saurabh Sinha; Justin Morrison; Alexa E. Walter; James J. Gugger; Andrea L.C. Schneider; Cian Dabrowski; Hannah Zamore; Leroy Wesley; Brigid Magdamo; Dmitriy Petrov; Junghoon J. Kim; Ramon Diaz-Arrastia; Danielle K. Sandsmark

NeuroImage: Clinical (Jan 2022)

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Jeffrey B. Ware,
Saurabh Sinha,
Justin Morrison,
Alexa E. Walter,
James J. Gugger,
Andrea L.C. Schneider,
Cian Dabrowski,
Hannah Zamore,
Leroy Wesley,
Brigid Magdamo,
Dmitriy Petrov,
Junghoon J. Kim,
Ramon Diaz-Arrastia,
Danielle K. Sandsmark

Affiliations

Jeffrey B. Ware: Division of Neuroradiology, Department of Radiology, Hospital of University of Pennsylvania, Perelman School of Medicine of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; Corresponding author.
Saurabh Sinha: Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Justin Morrison: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Alexa E. Walter: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
James J. Gugger: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Andrea L.C. Schneider: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Cian Dabrowski: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Hannah Zamore: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Leroy Wesley: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Brigid Magdamo: Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Dmitriy Petrov: Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Junghoon J. Kim: Department of Molecular, Cellular, and Biomedical Sciences, CUNY School of Medicine at The City College of New York, Townsend Harris Hall, 160 Convent Avenue, New York, NY 10031, USA
Ramon Diaz-Arrastia: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
Danielle K. Sandsmark: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA

Journal volume & issue: Vol. 36
p. 103236

Abstract

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Background and Purpose: Dysfunction of the blood–brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI. Materials and Methods: DCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (Ktrans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury. Results: TBI patients exhibited higher mean Ktrans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated Ktrans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = −0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level. Conclusions: This pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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