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Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies.

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.

SUBMITTER: Kannurpatti SS

PROVIDER: S-EPMC3923811 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies.

Kannurpatti Sridhar S SS Motes Michael A MA Biswal Bharat B BB Rypma Bart B

PloS one 20140213 2

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 g ...[more]

PMID: 24551151

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Project description:Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (n = 20; 25 ± 3 years) and older (n = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults (p < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (p < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (p < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.

Project description:The cerebral vascular network regulates blood flow distribution by adjusting vessel diameters, and consequently resistance to flow, in response to metabolic demands (neurovascular coupling) and changes in perfusion pressure (autoregulation). Deliberate changes in carbon dioxide (CO2) partial pressure may be used to challenge this regulation and assess its performance since CO2 also acts to change vessel diameter. Cerebrovascular reactivity (CVR), the ratio of cerebral blood flow (CBF) response to CO2 stimulus is currently used as a performance metric. However, the ability of CVR to reflect the responsiveness of a particular vascular region is confounded by that region's inclusion in the cerebral vascular network, where all regions respond to the global CO2 stimulus. Consequently, local CBF responses reflect not only changes in the local vascular resistance but also the effect of changes in local perfusion pressure resulting from redistribution of flow within the network. As a result, the CBF responses to CO2 take on various non-linear patterns that are not well-described by straight lines. We propose a method using a simple model to convert these CBF response patterns to the pattern of resistance responses that underlie them. The model, which has been used previously to explain the steal phenomenon, consists of two vascular branches in parallel fed by a major artery with a fixed resistance unchanging with CO2. One branch has a reference resistance with a sigmoidal response to CO2, representative of a voxel with a robust response. The other branch has a CBF equal to the measured CBF response to CO2 of any voxel under examination. Using the model to calculate resistance response patterns of the examined branch showed sigmoidal patterns of resistance response, regardless of the measured CBF response patterns. The sigmoid parameters of the resistance response pattern of examined voxels may be mapped to their anatomical location. We show an example for a healthy subject and for a patient with steno-occlusive disease to illustrate. We suggest that these maps provide physiological insight into the regulation of CBF distribution.

Project description:Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects' individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects' individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33-0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation.

Project description:Performing a BOLD functional MRI (fMRI) acquisition during breath-hold (BH) tasks is a non-invasive, robust method to estimate cerebrovascular reactivity (CVR). However, movement and breathing-related artefacts caused by the BH can substantially hinder CVR estimates due to their high temporal collinearity with the effect of interest, and attention has to be paid when choosing which analysis model should be applied to the data. In this study, we evaluate the performance of multiple analysis strategies based on lagged general linear models applied on multi-echo BOLD fMRI data, acquired in ten subjects performing a BH task during ten sessions, to obtain subject-specific CVR and haemodynamic lag estimates. The evaluated approaches range from conventional regression models, i.e. including drifts and motion timecourses as nuisance regressors, applied on single-echo or optimally-combined data, to more complex models including regressors obtained from multi-echo independent component analysis with different grades of orthogonalization in order to preserve the effect of interest, i.e. the CVR. We compare these models in terms of their ability to make signal intensity changes independent from motion, as well as the reliability as measured by voxelwise intraclass correlation coefficients of both CVR and lag maps over time. Our results reveal that a conservative independent component analysis model applied on the optimally-combined multi-echo fMRI signal offers the largest reduction of motion-related effects in the signal, while yielding reliable CVR amplitude and lag estimates, although a conventional regression model applied on the optimally-combined data results in similar estimates. This work demonstrates the usefulness of multi-echo based fMRI acquisitions and independent component analysis denoising for precision mapping of CVR in single subjects based on BH paradigms, fostering its potential as a clinically-viable neuroimaging tool for individual patients. It also proves that the way in which data-driven regressors should be incorporated in the analysis model is not straight-forward due to their complex interaction with the BH-induced BOLD response.

Dataset Information

Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies.

Publications

Assessment of unconstrained cerebrovascular reactivity marker for large age-range FMRI studies.

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