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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158222003011
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author 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
author_facet 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
author_sort Jeffrey B. Ware
collection DOAJ
description 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.
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spelling doaj.art-52f7ca57dd4046d8819122492aed000a2022-12-22T02:36:44ZengElsevierNeuroImage: Clinical2213-15822022-01-0136103236Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injuryJeffrey B. Ware0Saurabh Sinha1Justin Morrison2Alexa E. Walter3James J. Gugger4Andrea L.C. Schneider5Cian Dabrowski6Hannah Zamore7Leroy Wesley8Brigid Magdamo9Dmitriy Petrov10Junghoon J. Kim11Ramon Diaz-Arrastia12Danielle K. Sandsmark13Division 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.Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment 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, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment 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, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USADepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USABackground 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.http://www.sciencedirect.com/science/article/pii/S2213158222003011TBIDynamic contrast-enhanced MRIBlood–brain-barrierMicrovascular injury
spellingShingle 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
Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
NeuroImage: Clinical
TBI
Dynamic contrast-enhanced MRI
Blood–brain-barrier
Microvascular injury
title Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
title_full Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
title_fullStr Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
title_full_unstemmed Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
title_short Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury
title_sort dynamic contrast enhanced mri for characterization of blood brain barrier dysfunction after traumatic brain injury
topic TBI
Dynamic contrast-enhanced MRI
Blood–brain-barrier
Microvascular injury
url http://www.sciencedirect.com/science/article/pii/S2213158222003011
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