Characterizing a perfusion-based periventricular small vessel region of interest

Sudipto Dolui; Dylan Tisdall; Marta Vidorreta; David R. Jacobs; Ilya M. Nasrallah; R. Nick Bryan; David A. Wolk; John A. Detre

doi:10.1016/j.nicl.2019.101897

Characterizing a perfusion-based periventricular small vessel region of interest

Sudipto Dolui, Dylan Tisdall, Marta Vidorreta, David R. Jacobs, Ilya M. Nasrallah, R. Nick Bryan, David A. Wolk, John A. Detre

Epidemiology & Community Health

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

26 Scopus citations

Abstract

The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

Original language	English (US)
Article number	101897
Journal	NeuroImage: Clinical
Volume	23
DOIs	https://doi.org/10.1016/j.nicl.2019.101897
State	Published - 2019

Bibliographical note

Funding Information:
CARDIA is supported by contracts HHSN268201300025C , HHSN268201300026C , HHSN268 201300027C , HHSN268201300028C , HHSN268201300029C , and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729 , P41 EB015893 , R01 AG040271 , P30 AG010124 , R00 HD074649 and R03 AG063213 .

Funding Information:
CARDIA is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268 201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729, P41 EB015893, R01 AG040271, P30 AG010124, R00 HD074649 and R03 AG063213. The authors thank Dr. Joao Lima for his insightful comments.

Publisher Copyright:
© 2019

Keywords

Arterial spin labeling
Cerebral blood flow
Cerebral small vessel disease
Periventricular white matter
White matter lesions

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10.1016/j.nicl.2019.101897

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@article{2ee1d55bd3814c9a98b0bde45da5c79e,

title = "Characterizing a perfusion-based periventricular small vessel region of interest",

abstract = "The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.",

keywords = "Arterial spin labeling, Cerebral blood flow, Cerebral small vessel disease, Periventricular white matter, White matter lesions",

author = "Sudipto Dolui and Dylan Tisdall and Marta Vidorreta and Jacobs, {David R.} and Nasrallah, {Ilya M.} and Bryan, {R. Nick} and Wolk, {David A.} and Detre, {John A.}",

note = "Funding Information: CARDIA is supported by contracts HHSN268201300025C , HHSN268201300026C , HHSN268 201300027C , HHSN268201300028C , HHSN268201300029C , and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729 , P41 EB015893 , R01 AG040271 , P30 AG010124 , R00 HD074649 and R03 AG063213 . Funding Information: CARDIA is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268 201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729, P41 EB015893, R01 AG040271, P30 AG010124, R00 HD074649 and R03 AG063213. The authors thank Dr. Joao Lima for his insightful comments. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

doi = "10.1016/j.nicl.2019.101897",

language = "English (US)",

volume = "23",

journal = "NeuroImage: Clinical",

issn = "2213-1582",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Characterizing a perfusion-based periventricular small vessel region of interest

AU - Dolui, Sudipto

AU - Tisdall, Dylan

AU - Vidorreta, Marta

AU - Jacobs, David R.

AU - Nasrallah, Ilya M.

AU - Bryan, R. Nick

AU - Wolk, David A.

AU - Detre, John A.

N1 - Funding Information: CARDIA is supported by contracts HHSN268201300025C , HHSN268201300026C , HHSN268 201300027C , HHSN268201300028C , HHSN268201300029C , and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729 , P41 EB015893 , R01 AG040271 , P30 AG010124 , R00 HD074649 and R03 AG063213 . Funding Information: CARDIA is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268 201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging. This study was further supported by NIH grants R01 MH080729, P41 EB015893, R01 AG040271, P30 AG010124, R00 HD074649 and R03 AG063213. The authors thank Dr. Joao Lima for his insightful comments. Publisher Copyright: © 2019

PY - 2019

Y1 - 2019

N2 - The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

AB - The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

KW - Arterial spin labeling

KW - Cerebral blood flow

KW - Cerebral small vessel disease

KW - Periventricular white matter

KW - White matter lesions

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DO - 10.1016/j.nicl.2019.101897

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AN - SCOPUS:85067582763

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VL - 23

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 101897

ER -

Characterizing a perfusion-based periventricular small vessel region of interest

Abstract

Bibliographical note

Keywords

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