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Comparative Evaluation of Resting-State and CO2-Induced Cerebrovascular Reactivity in Patients with Traumatic Brain Injury

delete2025-12-01
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PRE
AI
D
D.Y. Kim
J
Joosup Kim
Y
Yechan Kim
D
Dominique Duncan
F
Franck Amyot
K
Kimbra Kenney
R
Ramon Diaz‐Arrastia *
C
Choi, Joon Yul *
DOI:10.1177/08977151251407598delete
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Abstract

Abstract

En 中文
Cerebrovascular reactivity (CVR) mapping is a promising biomarker for evaluating vascular dysfunction following traumatic brain injury (TBI). Traditional CVR assessment requires carbon dioxide (CO2) administration. Assessing CVR from resting-state blood-oxygen-level-dependent (BOLD) sequences (RS-CVR) offers a task-free alternative, but its validity in TBI has not yet been established. We aimed to evaluate whether RS-CVR can reliably detect cerebrovascular impairment in patients with TBI by comparing it with CO2-inhalation CVR (CO2-CVR). We enrolled 23 chronic moderate-to-severe TBI patients and 13 healthy controls (HC) who underwent both CO2-CVR and RS-CVR imaging using BOLD functional magnetic resonance imaging (BOLD fMRI). RS-CVR maps were computed using a voxel-wise general linear model (GLM) across 120 bandpass filters. Spatial correlations between RS-CVR and CO2-CVR were calculated to identify the optimal frequency bands. Z-score analyses and lesion-based comparisons were performed to assess CVR reductions in TBI. In the TBI cohort, lesion-based CVR was correlated with clinical outcomes using GLM adjusted for age and sex. The highest whole-brain spatial correlation between RS-CVR and CO2-CVR in HC occurred at [0-116.4 mHz] (r = 0.5239 +/- 0.1107). In TBI, the peak correlation slightly shifted to [0-74.5 mHz] (r = 0.5217 +/- 0.1108) but remained comparable at [0-116.4 mHz] (r = 0.5093 +/- 0.1263). As expected, regions of encephalomalacia, fluid-attenuated inversion recovery hyperintensity, showed CVR reductions on RS-CVR and CO2-CVR maps, but low CVR was also identified through both methods in normal-appearing brain tissue. Across lesion areas, RS-CVR detected deficits consistent with CO2-CVR, with mean z-scores of -0.217 +/- 0.334 and -0.391 +/- 0.294 for encephalomalacia and hyperintensities, respectively. Lesion-based CVR values were associated with clinical outcomes, with both CO2-CVR and RS-CVR positively correlated with days in the intensive care unit (ICU; p < 0.05) and showing negative associations with Rivermead post-concussion symptoms questionnaire scores, statistically significant for CO2-CVR (p = 0.031) and trending for RS-CVR (p = 0.089). RS-CVR closely mirrors CO2-CVR in both global and lesion-specific analyses, validating its use as a noninvasive method for detecting vascular deficits in TBI. This task-free and scalable tool for cerebrovascular assessment offers a valuable approach for characterizing vascular health relevant to TBI prognosis and guiding neurorehabilitation efforts.
Keywords:
cerebrovascular reactivity
hypercapnia
resting-state fMRI
traumatic brain injury
vascular dysfunction

Journal

Journal of Neurotrauma cover
Journal of Neurotrauma
IF:
3.8
Papers:
5.6K
Citations:
1.7W

Organization

W
walter reed national military medical center
Scholars:
44
Papers: 21
Citations: 0
U
University of Pennsylvania
Scholars:
1.0W
Papers: 3.7K
Citations: 11.8W
Y
yonsei university
Scholars:
3.7K
Papers: 1.5K
Citations: 0
C
city university of new york (cuny) system
Scholars:
1.6W
Papers: 1.5W
Citations: 26
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