Dataset Information

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

ABSTRACT:

Objective

To improve quantitative cerebrovascular reactivity (CVR) measurements and CO ₂ arrival times, we present an iterative analysis capable of decomposing different temporal components of the dynamic carbon dioxide- Blood Oxygen-Level Dependent (CO ₂-BOLD) relationship.

Experimental design

Decomposition of the dynamic parameters included a redefinition of the voxel-wise CO ₂ arrival time, and a separation from the vascular response to a stepwise increase in CO ₂ (Delay to signal Plateau - DTP) and a decrease in CO ₂ (Delay to signal Baseline -DTB). Twenty-five (normal) datasets, obtained from BOLD MRI combined with a standardized pseudo-square wave CO ₂ change, were co-registered to generate reference atlases for the aforementioned dynamic processes to score the voxel-by-voxel deviation probability from normal range. This analysis is further illustrated in two subjects with unilateral carotid artery occlusion using these reference atlases.

Principal observations

We have found that our redefined CO ₂ arrival time resulted in the best data fit. Additionally, excluding both dynamic BOLD phases (DTP and DTB) resulted in a static CVR, that is maximal response, defined as CVR calculated only over a normocapnic and hypercapnic calibrated plateau.

Conclusion

Decomposition and novel iterative modeling of different temporal components of the dynamic CO ₂-BOLD relationship improves quantitative CVR measurements.

SUBMITTER: van Niftrik CHB

PROVIDER: S-EPMC5607533 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

van Niftrik Christiaan Hendrik Bas CHB Piccirelli Marco M Bozinov Oliver O Pangalu Athina A Fisher Joseph A JA Valavanis Antonios A Luft Andreas R AR Weller Michael M Regli Luca L Fierstra Jorn J

Brain and behavior 20170726 9

<h4>Objective</h4>To improve quantitative cerebrovascular reactivity (CVR) measurements and CO <sub>2</sub> arrival times, we present an iterative analysis capable of decomposing different temporal components of the dynamic carbon dioxide- Blood Oxygen-Level Dependent (CO <sub>2</sub>-BOLD) relationship.<h4>Experimental design</h4>Decomposition of the dynamic parameters included a redefinition of the voxel-wise CO <sub>2</sub> arrival time, and a separation from the vascular response to a stepwi ...[more]

PMID: 28948064

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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:Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict, has been shown to provide valuable information in the diagnosis and treatment evaluation of patients with various cerebrovascular conditions. CVR mapping is typically performed using hypercapnic gas inhalation as a vasoactive challenge while collecting BOLD images, but the inherent need of gas inhalation and the associated apparatus setup present a practical obstacle in applying it in routine clinical use. Therefore, we aimed to develop a new method to map CVR using resting-state BOLD data without the need of gas inhalation. This approach exploits the natural variation in respiration and measures its influence on BOLD MRI signal. In this work, we first identified a surrogate of the arterial CO2 fluctuation during spontaneous breathing from the global BOLD signal. Second, we tested the feasibility and reproducibility of the proposed approach to use the above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we validated the "resting-state CVR map" with a conventional CVR map obtained with hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility of this new approach in detecting abnormal CVR in a group of patients with Moyamoya disease, and again validated the results using the conventional gas inhalation method. Our results showed that global BOLD signal fluctuation in the frequency range of 0.02-0.04Hz contains the most prominent contribution from natural variation in arterial CO2. The CVR map calculated using this signal as a regressor is reproducible across runs (ICC=0.91±0.06), and manifests a strong spatial correlation with results measured with a conventional hypercapnia-based method in healthy subjects (r=0.88, p<0.001). We also found that resting-state CVR was able to identify vasodilatory deficit in patients with steno-occlusive disease, the spatial pattern of which matches that obtained using the conventional gas method (r=0.71±0.18). These results suggest that CVR obtained with resting-state BOLD may be a useful alternative in detecting vascular deficits in clinical applications when gas challenge is not feasible.

Project description:Cerebrovascular reactivity (CVR), an index of brain vessel's dilatory capacity, is typically measured using hypercapnic gas inhalation or breath-holding as a vasoactive challenge. However, these methods require considerable subject cooperation and could be challenging in clinical studies. More recently, there have been attempts to use resting-state BOLD data to map CVR by utilizing spontaneous changes in breathing pattern. However, in subjects who have small fluctuations in their spontaneous breathing pattern, the CVR results could be noisy and unreliable. In this study, we aim to develop a new method for CVR mapping that does not require gas-inhalation yet provides substantially higher sensitivity than resting-state CVR mapping. This new method is largely based on resting-state scan, but introduces intermittent modulation of breathing pattern in the subject to enhance fluctuations in their end-tidal CO2 (EtCO2) level. Here we examined the comfort level, sensitivity, and accuracy of this method in two studies. First, in 8 healthy young subjects, we developed the intermittent breath-modulation method using two different modulation frequencies, 6 s per breath and 12 s per breath, respectively, and compared the results to three existing CVR methods, specifically hypercapnic gas inhalation, breath-holding, and resting-state. Our results showed that the comfort level of the 6-s breath-modulation method was significantly higher than breath-holding (p = 0.007) and CO2-inhalation (p = 0.015) methods, while not different from the resting-state, i.e. free breathing method (p = 0.52). When comparing the sensitivity of CVR methods, the breath-modulation methods revealed higher Z-statistics compared to the resting-state scan (p < 0.008) and was comparable to breath-holding results. Next, we tested the feasibility of breath-modulation CVR mapping (6 s per breath) in 21 cognitively normal elderly participants and compared quantitative CVR values to that obtained with the CO2-inhalation method. Whole-brain CVR was found to be 0.150 ± 0.055 and 0.154 ± 0.032 %ΔBOLD/mmHg for the breath-modulation and CO2-inhalation method, respectively, with a significant correlation between them (y = 0.97x, p = 0.007). CVR mapping with intermittent breath modulation may be a useful method that combines the advantages of resting-state and CO2-inhalation based approaches.

Project description:In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50-69% stenosis, 70-90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class - including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.

Dataset Information

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

Objective

Experimental design

Principal observations

Conclusion

Publications

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

Similar Datasets

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