Quantitative Water Permeability Mapping of Blood-Brain-Barrier Dysfunction in Aging
Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k W ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI....
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| Published in: | Frontiers in aging neuroscience Vol. 14; p. 867452 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Frontiers Media S.A
08.04.2022
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| ISSN: | 1663-4365, 1663-4365 |
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| Abstract | Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k
W
) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k
W
in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k
W
values in the cerebral cortex (mean = 81.51 min
–1
,
SD
= 15.54) compared to cerebral white matter (mean = 75.19 min
–1
,
SD
= 13.85) (
p
< 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k
W
as an outcome showed that age was statistically significant in the cerebral cortex (
p
= 0.013), cerebral white matter (
p
= 0.033), hippocampi (
p
= 0.043), orbitofrontal cortices (
p
= 0.042), and precunei cortices (
p
= 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex (
p
= 0.026) and precunei cortices (
p
= 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k
W
and WMH volume (
r
= −0.51,
p
= 0.02), and normal-appearing white matter (NAWM) and WMH volume (
r
= −0.44,
p
= 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders. |
|---|---|
| AbstractList | Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (kW) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific kW in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher kW values in the cerebral cortex (mean = 81.51 min–1, SD = 15.54) compared to cerebral white matter (mean = 75.19 min–1, SD = 13.85) (p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with kW as an outcome showed that age was statistically significant in the cerebral cortex (p = 0.013), cerebral white matter (p = 0.033), hippocampi (p = 0.043), orbitofrontal cortices (p = 0.042), and precunei cortices (p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex (p = 0.026) and precunei cortices (p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) kW and WMH volume (r = −0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume (r = −0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders. Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer's disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (kW) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific kW in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher kW values in the cerebral cortex (mean = 81.51 min-1, SD = 15.54) compared to cerebral white matter (mean = 75.19 min-1, SD = 13.85) (p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with kW as an outcome showed that age was statistically significant in the cerebral cortex (p = 0.013), cerebral white matter (p = 0.033), hippocampi (p = 0.043), orbitofrontal cortices (p = 0.042), and precunei cortices (p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex (p = 0.026) and precunei cortices (p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) kW and WMH volume (r = -0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume (r = -0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders.Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer's disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (kW) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific kW in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher kW values in the cerebral cortex (mean = 81.51 min-1, SD = 15.54) compared to cerebral white matter (mean = 75.19 min-1, SD = 13.85) (p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with kW as an outcome showed that age was statistically significant in the cerebral cortex (p = 0.013), cerebral white matter (p = 0.033), hippocampi (p = 0.043), orbitofrontal cortices (p = 0.042), and precunei cortices (p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex (p = 0.026) and precunei cortices (p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) kW and WMH volume (r = -0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume (r = -0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders. Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer's disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k values in the cerebral cortex (mean = 81.51 min , = 15.54) compared to cerebral white matter (mean = 75.19 min , = 13.85) ( < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k as an outcome showed that age was statistically significant in the cerebral cortex ( = 0.013), cerebral white matter ( = 0.033), hippocampi ( = 0.043), orbitofrontal cortices ( = 0.042), and precunei cortices ( = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex ( = 0.026) and precunei cortices ( = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k and WMH volume ( = -0.51, = 0.02), and normal-appearing white matter (NAWM) and WMH volume ( = -0.44, = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders. Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k W ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k W in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k W values in the cerebral cortex (mean = 81.51 min –1 , SD = 15.54) compared to cerebral white matter (mean = 75.19 min –1 , SD = 13.85) ( p < 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k W as an outcome showed that age was statistically significant in the cerebral cortex ( p = 0.013), cerebral white matter ( p = 0.033), hippocampi ( p = 0.043), orbitofrontal cortices ( p = 0.042), and precunei cortices ( p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex ( p = 0.026) and precunei cortices ( p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k W and WMH volume ( r = −0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume ( r = −0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders. |
| Author | Sweeney, Elizabeth M. Merkler, Alexander E. Nguyen, Thanh D. Zhang, Qihao Ivanidze, Jana de Leon, Mony J. Ford, Jeremy N. Gupta, Ajay |
| AuthorAffiliation | 2 Department of Radiology, Weill Cornell Medicine , New York, NY , United States 1 Department of Radiology, Massachusetts General Hospital , Boston, MA , United States 3 Department of Biostatistics, University of Pennsylvania , Philadelphia, PA , United States 4 Department of Neurology, Weill Cornell Medicine , New York, NY , United States |
| AuthorAffiliation_xml | – name: 3 Department of Biostatistics, University of Pennsylvania , Philadelphia, PA , United States – name: 4 Department of Neurology, Weill Cornell Medicine , New York, NY , United States – name: 1 Department of Radiology, Massachusetts General Hospital , Boston, MA , United States – name: 2 Department of Radiology, Weill Cornell Medicine , New York, NY , United States |
| Author_xml | – sequence: 1 givenname: Jeremy N. surname: Ford fullname: Ford, Jeremy N. – sequence: 2 givenname: Qihao surname: Zhang fullname: Zhang, Qihao – sequence: 3 givenname: Elizabeth M. surname: Sweeney fullname: Sweeney, Elizabeth M. – sequence: 4 givenname: Alexander E. surname: Merkler fullname: Merkler, Alexander E. – sequence: 5 givenname: Mony J. surname: de Leon fullname: de Leon, Mony J. – sequence: 6 givenname: Ajay surname: Gupta fullname: Gupta, Ajay – sequence: 7 givenname: Thanh D. surname: Nguyen fullname: Nguyen, Thanh D. – sequence: 8 givenname: Jana surname: Ivanidze fullname: Ivanidze, Jana |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35462701$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2022 Ford, Zhang, Sweeney, Merkler, de Leon, Gupta, Nguyen and Ivanidze. Copyright © 2022 Ford, Zhang, Sweeney, Merkler, de Leon, Gupta, Nguyen and Ivanidze. 2022 Ford, Zhang, Sweeney, Merkler, de Leon, Gupta, Nguyen and Ivanidze |
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| Keywords | blood-brain barrier glymphatic cerebral small vessel disease aging arterial spin labeling |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience Edited by: Eszter Farkas, University of Szeged, Hungary Reviewed by: Alon Friedman, Dalhousie University, Canada; Donald Elbert, The University of Texas at Austin, United States; Istvan Krizbai, Hungarian Academy of Sciences (MTA), Hungary |
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| Title | Quantitative Water Permeability Mapping of Blood-Brain-Barrier Dysfunction in Aging |
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