Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging

Valerie C. Anderson; Ian J. Tagge; Xin Li; Joseph F. Quinn; Jeffrey A. Kaye; Dennis N. Bourdette; Rebecca I. Spain; Louis P. Riccelli; Manoj K. Sammi; Charles S. Springer; William D. Rooney

doi:10.1111/jon.12744

Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging

Valerie C. Anderson, Ian J. Tagge, Xin Li, Joseph F. Quinn, Jeffrey A. Kaye, Dennis N. Bourdette, Rebecca I. Spain, Louis P. Riccelli, Manoj K. Sammi, Charles S. Springer, William D. Rooney

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

6 Scopus citations

Abstract

BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood–brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (v_b) and capillary water efflux rate constant (k_po) were determined by fitting changes in the ¹H₂O longitudinal relaxation rate constant (R₁) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R₁ values and WM volume showed similar trajectories of age-related decline. Among all subjects, v_b and k_po averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s⁻¹, respectively. While v_b showed minimal changes over the 40-year-age span of participants, k_po declined 0.06 s⁻¹ (ca. 3%) per year (r = −.66; P '.0005), from near 4 s⁻¹ at age 30 to ca. 2 s⁻¹ at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that k_po tracks Na⁺, K⁺-ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in k_po observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.

Original language	English (US)
Pages (from-to)	658-665
Number of pages	8
Journal	Journal of Neuroimaging
Volume	30
Issue number	5
DOIs	https://doi.org/10.1111/jon.12744
State	Published - Sep 1 2020

Keywords

Aging
blood brain barrier, DCE-MRI, water cycling
white matter

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Clinical Neurology

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10.1111/jon.12744

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@article{0b4fc9d36f8745768d51e4904bd01506,

title = "Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging",

abstract = "BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood–brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (vb) and capillary water efflux rate constant (kpo) were determined by fitting changes in the 1H2O longitudinal relaxation rate constant (R1) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R1 values and WM volume showed similar trajectories of age-related decline. Among all subjects, vb and kpo averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s−1, respectively. While vb showed minimal changes over the 40-year-age span of participants, kpo declined 0.06 s−1 (ca. 3%) per year (r = −.66; P '.0005), from near 4 s−1 at age 30 to ca. 2 s−1 at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that kpo tracks Na+, K+-ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in kpo observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.",

keywords = "Aging, blood brain barrier, DCE-MRI, water cycling, white matter",

author = "Anderson, {Valerie C.} and Tagge, {Ian J.} and Xin Li and Quinn, {Joseph F.} and Kaye, {Jeffrey A.} and Bourdette, {Dennis N.} and Spain, {Rebecca I.} and Riccelli, {Louis P.} and Sammi, {Manoj K.} and Springer, {Charles S.} and Rooney, {William D.}",

note = "Publisher Copyright: {\textcopyright} 2020 American Society of Neuroimaging",

year = "2020",

month = sep,

day = "1",

doi = "10.1111/jon.12744",

language = "English (US)",

volume = "30",

pages = "658--665",

journal = "Journal of Neuroimaging",

issn = "1051-2284",

publisher = "Wiley-Blackwell",

number = "5",

}

TY - JOUR

T1 - Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging

AU - Anderson, Valerie C.

AU - Tagge, Ian J.

AU - Li, Xin

AU - Quinn, Joseph F.

AU - Kaye, Jeffrey A.

AU - Bourdette, Dennis N.

AU - Spain, Rebecca I.

AU - Riccelli, Louis P.

AU - Sammi, Manoj K.

AU - Springer, Charles S.

AU - Rooney, William D.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood–brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (vb) and capillary water efflux rate constant (kpo) were determined by fitting changes in the 1H2O longitudinal relaxation rate constant (R1) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R1 values and WM volume showed similar trajectories of age-related decline. Among all subjects, vb and kpo averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s−1, respectively. While vb showed minimal changes over the 40-year-age span of participants, kpo declined 0.06 s−1 (ca. 3%) per year (r = −.66; P '.0005), from near 4 s−1 at age 30 to ca. 2 s−1 at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that kpo tracks Na+, K+-ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in kpo observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.

AB - BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood–brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (vb) and capillary water efflux rate constant (kpo) were determined by fitting changes in the 1H2O longitudinal relaxation rate constant (R1) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R1 values and WM volume showed similar trajectories of age-related decline. Among all subjects, vb and kpo averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s−1, respectively. While vb showed minimal changes over the 40-year-age span of participants, kpo declined 0.06 s−1 (ca. 3%) per year (r = −.66; P '.0005), from near 4 s−1 at age 30 to ca. 2 s−1 at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that kpo tracks Na+, K+-ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in kpo observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.

KW - Aging

KW - blood brain barrier, DCE-MRI, water cycling

KW - white matter

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U2 - 10.1111/jon.12744

DO - 10.1111/jon.12744

M3 - Article

C2 - 32558031

AN - SCOPUS:85086520104

SN - 1051-2284

VL - 30

SP - 658

EP - 665

JO - Journal of Neuroimaging

JF - Journal of Neuroimaging

IS - 5

ER -

Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging

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Keywords

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