Abstract
Breath hold (BH), a commonly used task to measure cerebrovascular reactivity (CVR) in fMRI studies varies in outcome among individuals due to subject-physiology and/or BH-inspiration/expiration differences (i.e., performance). In prior age-related fMRI studies, smaller task-related BOLD response variability is observed among younger than older individuals. Also, a linear CVR versus task relationship exists in younger individuals which maybe useful to test the accuracy of CVR responses in older groups. Hence we hypothesized that subject-related physiological and/or BH differences, if present, may compromise CVR versus task linearity in older individuals. To test the hypothesis, empirical BH versus task relationships from motor and cognitive areas were obtained in younger (mean age = 26 years) and older (mean age = 58 years) human subjects. BH versus task linearity was observed only in the younger group, confirming our hypothesis. Further analysis indicated BH responses and its variability to be similar in both younger and older groups, suggesting that BH may not accurately represent CVR in a large age range. Using the resting state fluctuation of amplitude (RSFA) as an unconstrained alternative to BH, subject-wise correspondence between BH and RSFA was tested. Correlation between BH versus RSFA was significant within the motor but was not significant in the cognitive areas in the younger and was completely disrupted in both areas in the older subjects indicating that BH responses are constrained by subject-related physiology and/or performance-related differences. Contrasting BH to task, RSFA-task relationships were independent of age accompanied by age-related increases in CVR variability as measured by RSFA, not observed with BH. Together the results obtained indicate that RSFA accurately represents CVR in any age range avoiding multiple and yet unknown physiologic and task-related pitfalls of BH.
Highlights
A broad definition of cerebrovascular reactivity (CVR) is the ability of cerebrovasculature to respond to chemical agents or CO2 changes in the form of vasodilation or vasoconstriction
We propose that the unconstrained CVR marker resting state fluctuation of amplitude (RSFA), available from a resting functional Magnetic Resonance Imaging (fMRI) scan, well-tolerated by special populations, is a better option than breath hold (BH) for measuring CVR in larger age ranges
A subject-wise analysis was followed in this study as previous age-dependent BH-task relationships have shown no apparent differences at the voxel level [11,18,19,28,29]
Summary
A broad definition of cerebrovascular reactivity (CVR) is the ability of cerebrovasculature to respond to chemical agents or CO2 changes in the form of vasodilation or vasoconstriction. A feasible application of functional Magnetic Resonance Imaging (fMRI) to clinical assessment of CVR requires less invasive methods to evoke vascular activity To this end, carbon-dioxide (CO2), supplied through a breathing-mask to subjects have been utilized. Special groups such as chronic obstructive pulmonary disease (COPD) patients are often excluded from CO2 breathing studies using gas-masks narrowing the subject pool Alternatives such as the breath hold (BH) task have been utilized to produce mild hypercapnia in a matter of seconds [10], comparable to breathing a mixture of CO2 gas and air and is generally considered a reliable CVR measurement method for fMRI applications [1,2,3,11,12]. BH experiments and the variability of outcomes due to uncontrollable internal physiological factors must be critically considered and are often challenging to streamline, no matter how hard the subject or patient may try [15]
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