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J Cereb Blood Flow Metab. 2017 Jul;37(7):2526-2538. doi: 10.1177/0271678X16670921. Epub 2016 Jan 1.

Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge?

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1 Department of Radiology, Stanford University, Stanford, CA, USA.
2 Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
3 Departments of Neurology and Public Health Sciences, and the Neuroscience Program, Evelyn F. McKnight Brain Institute, University of Miami, Miami, FL, USA.
4 Geriatric Research and Education Clinical Center, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA.
5 Division of Nephrology, Stanford University, Stanford, CA, USA.


Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R2 = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.


Blood oxygenation level-dependent contrast; brain imaging; breath-holding challenge; cerebral hemodynamics; cerebrospinal fluid; cerebrovascular disease; functional magnetic resonance imaging; hemodynamics; magnetic resonance; magnetic resonance imaging; resting state fMRI; vascular cognitive impairment

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