MTT and blood-brain barrier disruption within asymptomatic vascular WM lesions

B. E. Dewey; X. Xu; L. Knutsson; A. Jog; J. L. Prince; P. B. Barker; P. C.M. van Zijl; R. Leigh; Paul Nyquist

doi:10.3174/ajnr.A7165

MTT and blood-brain barrier disruption within asymptomatic vascular WM lesions

B. E. Dewey, X. Xu, L. Knutsson, A. Jog, J. L. Prince, P. B. Barker, P. C.M. van Zijl, R. Leigh, Paul Nyquist

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes^-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes^-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P,.046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

Original language	English (US)
Pages (from-to)	1396-1402
Number of pages	7
Journal	American Journal of Neuroradiology
Volume	42
Issue number	8
DOIs	https://doi.org/10.3174/ajnr.A7165
State	Published - Aug 1 2021

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Clinical Neurology

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@article{7f3ecdd2711045d5b4dd9d8b83e759eb,

title = "MTT and blood-brain barrier disruption within asymptomatic vascular WM lesions",

abstract = "BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P,.046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.",

author = "Dewey, {B. E.} and X. Xu and L. Knutsson and A. Jog and Prince, {J. L.} and Barker, {P. B.} and {van Zijl}, {P. C.M.} and R. Leigh and Paul Nyquist",

note = "Funding Information: Received October 16, 2020; accepted after revision March 13, 2021. From the Departments of Electrical and Computer Engineering (B.E.D., J.L.P.) and Radiology and Radiological Science (X.X., L.K., J.L.P., P.B.B., P.C.M.v.Z.), Division of MRI Research, and Department of Neurology (R.L., P.N.), Johns Hopkins University, Baltimore, Maryland; F.M. Kirby Research Center for Functional Brain Imaging (B.E.D., X.X., P.B.B., P.C.M.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland; Department of Medical Radiation Physics (L.K.), Lund University, Lund, Sweden; and Athinoula A. Martinos Center for Biomedical Imaging (A.J.), Harvard University Medical School, Boston Massachusetts. B.E. Dewey and X. Xu contributed equally to this work. This work was supported by funding from the National Institutes of Health– National Institute of Neurological Disorders and Stroke (R01NS062059) and the Johns Hopkins Department of Anesthesia, Stimulating and Advancing ACCM Research award. Funding Information: This work was supported by funding from the National Institutes of Health-National Institute of Neurological Disorders and Stroke (R01NS062059) and the Johns Hopkins Department of Anesthesia, Stimulating and Advancing ACCM Research award. Publisher Copyright: {\textcopyright} 2021 American Society of Neuroradiology. All rights reserved.",

year = "2021",

month = aug,

day = "1",

doi = "10.3174/ajnr.A7165",

language = "English (US)",

volume = "42",

pages = "1396--1402",

journal = "American Journal of Neuroradiology",

issn = "0195-6108",

publisher = "American Society of Neuroradiology",

number = "8",

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TY - JOUR

T1 - MTT and blood-brain barrier disruption within asymptomatic vascular WM lesions

AU - Dewey, B. E.

AU - Xu, X.

AU - Knutsson, L.

AU - Jog, A.

AU - Prince, J. L.

AU - Barker, P. B.

AU - van Zijl, P. C.M.

AU - Leigh, R.

AU - Nyquist, Paul

N1 - Funding Information: Received October 16, 2020; accepted after revision March 13, 2021. From the Departments of Electrical and Computer Engineering (B.E.D., J.L.P.) and Radiology and Radiological Science (X.X., L.K., J.L.P., P.B.B., P.C.M.v.Z.), Division of MRI Research, and Department of Neurology (R.L., P.N.), Johns Hopkins University, Baltimore, Maryland; F.M. Kirby Research Center for Functional Brain Imaging (B.E.D., X.X., P.B.B., P.C.M.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland; Department of Medical Radiation Physics (L.K.), Lund University, Lund, Sweden; and Athinoula A. Martinos Center for Biomedical Imaging (A.J.), Harvard University Medical School, Boston Massachusetts. B.E. Dewey and X. Xu contributed equally to this work. This work was supported by funding from the National Institutes of Health– National Institute of Neurological Disorders and Stroke (R01NS062059) and the Johns Hopkins Department of Anesthesia, Stimulating and Advancing ACCM Research award. Funding Information: This work was supported by funding from the National Institutes of Health-National Institute of Neurological Disorders and Stroke (R01NS062059) and the Johns Hopkins Department of Anesthesia, Stimulating and Advancing ACCM Research award. Publisher Copyright: © 2021 American Society of Neuroradiology. All rights reserved.

PY - 2021/8/1

Y1 - 2021/8/1

N2 - BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P,.046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

AB - BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P,.046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

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DO - 10.3174/ajnr.A7165

M3 - Article

C2 - 34083262

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SN - 0195-6108

VL - 42

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EP - 1402

JO - American Journal of Neuroradiology

JF - American Journal of Neuroradiology

IS - 8

ER -

MTT and blood-brain barrier disruption within asymptomatic vascular WM lesions

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