122 research outputs found

    Respiratory challenge MRI: practical aspects

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    Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques

    Lag-Optimized Blood Oxygenation Level Dependent Cerebrovascular Reactivity Estimates Derived From Breathing Task Data Have a Stronger Relationship With Baseline Cerebral Blood Flow

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    Published: 15 June 2022Cerebrovascular reactivity (CVR), an important indicator of cerebrovascular health, is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. Theoretical and empirical evidence suggests that baseline cerebral blood flow (CBF) modulates BOLD signal amplitude and may influence BOLD-CVR estimates. We address how acquisition and modeling choices affect the relationship between baseline cerebral blood flow (bCBF) and BOLD-CVR: whether BOLD-CVR is modeled with the inclusion of a breathing task, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. We assessed between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a breathing task addition to a resting-state acquisition, alongside lag-optimization within BOLD-CVR modeling, can improve BOLD-CVR correlations with bCBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive correlations between bCBF and BOLD-CVR, both between- and within-subjects. The physiological explanation of this positive correlation is unclear; research with larger samples and tightly controlled vasoactive stimuli is needed. Insights into what drives variability in BOLD-CVR measurements and related measurements of cerebrovascular function are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve.This work was supported by the Center for Translational Imaging at Northwestern University. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [K12HD073945]. KZ was supported by an NIH-funded training program [T32EB025766]. SM was supported by the European Unionā€™s Horizon 2020 research and innovation program [Marie Skłodowska-Curie grant agreement No. 713673] and a fellowship from La Caixa Foundation [ID 100010434, fellowship code LCF/BQ/IN17/11620063]. CC-G was supported by the Spanish Ministry of Economy and Competitiveness [Ramon y Cajal Fellowship, RYC2017-21845], the Basque Government [BERC 2018-2021 and PIBA_2019_104], and the Spanish Ministry of Science, Innovation and Universities [MICINN; PID2019- 105520GB-100]

    Multi-Vendor and Multisite Evaluation of Cerebrovascular Reactivity Mapping Using Hypercapnia Challenge

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    Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain\u27s vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate the reliability of CO2-CVR quantification in three studies. First, the inter-rater reliability of CO2-CVR data processing was evaluated by having raters from 5 MarkVCID sites process the same 30 CVR datasets using a cloud-based CVR data processing pipeline. Second, the inter-scanner reproducibility of CO2-CVR quantification was assessed in 10 young subjects across two scanners of different vendors. Third, test-retest repeatability was evaluated in 20 elderly subjects from 4 sites with a scan interval of less than 2 weeks. In all studies, the CO2 CVR measurements were performed using the fixed inspiration method, where the subjects wore a nose clip and a mouthpiece and breathed room air and 5% CO2 air contained in a Douglas bag alternatively through their mouth. The results showed that the inter-rater CoV of CVR processing was 0.08 Ā± 0.08% for whole-brain CVR values and ranged from 0.16% to 0.88% in major brain regions, with ICC of absolute agreement above 0.9959 for all brain regions. Inter-scanner CoV was found to be 6.90 Ā± 5.08% for whole-brain CVR values, and ranged from 4.69% to 12.71% in major brain regions, which are comparable to intra-session CoVs obtained from the same scanners on the same day. ICC of consistency between the two scanners was 0.8498 for whole-brain CVR and ranged from 0.8052 to 0.9185 across major brain regions. In the test-retest evaluation, test-retest CoV across different days was found to be 18.29 Ā± 17.12% for whole-brain CVR values, and ranged from 16.58% to 19.52% in major brain regions, with ICC of absolute agreement ranged from 0.6480 to 0.7785. These results demonstrated good inter-rater, inter-scanner, and test-retest reliability in healthy volunteers, and suggested that CO2-CVR has suitable instrumental properties for use as an imaging biomarker of cerebrovascular function in multi-site and longitudinal observational studies and clinical trials

    MRI-based cerebrovascular reactivity using transfer function analysis reveals temporal group differences between patients with sickle cell disease and healthy controls

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    AbstractObjectivesCerebrovascular reactivity (CVR) measures the ability of cerebral blood vessels to change their diameter and, hence, their capacity to regulate regional blood flow in the brain. High resolution quantitative maps of CVR can be produced using blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with a carbon dioxide stimulus, and these maps have become a useful tool in the clinical evaluation of cerebrovascular disorders. However, conventional CVR analysis does not fully characterize the BOLD response to a stimulus as certain regions of the brain are slower to react to the stimulus than others, especially in disease. Transfer function analysis (TFA) is an alternative technique that can account for dynamic temporal relations between signals and has recently been adapted for CVR computation. We investigated the application of TFA in data on children with sickle cell disease (SCD) and healthy controls, and compared them to results derived from conventional CVR analysis.Materials and methodsData from 62 pediatric patients with SCD and 34 age-matched healthy controls were processed using conventional CVR analysis and TFA. BOLD data were acquired on a 3Tesla MRI scanner while a carbon dioxide stimulus was quantified by sampling the end-tidal partial pressures of each exhaled breath. In addition, T1 weighted structural imaging was performed to identify grey and white matter regions for analysis. The TFA method generated maps representing both the relative magnitude change of the BOLD signal in response to the stimulus (Gain), as well as the BOLD signal speed of response (Phase) for each subject. These were compared to CVR maps calculated from conventional analysis. The effect of applying TFA on data from SCD patients versus controls was also examined.ResultsThe Gain measures derived from TFA were significantly higher than CVR values based on conventional analysis in both SCD patients and healthy controls, but the difference was greater in the SCD data. Moreover, while these differences were uniform across the grey and white matter regions of controls, they were greater in white matter than grey matter in the SCD group. Phase was also shown to be significantly correlated with the amount that TFA increases CVR estimates in both the grey and white matter.ConclusionsWe demonstrated that conventional CVR analysis underestimates vessel reactivity and this effect is more prominent in patients with SCD. By using TFA, the resulting Gain and Phase measures more accurately characterize the BOLD response as it accounts for the temporal dynamics responsible for the CVR underestimation. We suggest that the additional information offered through TFA can provide insight into the mechanisms underlying CVR compromise in cerebrovascular diseases

    Arterial stiffness and brain health : investigating the impact of sex-related differences

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    Introduction: Il est bien eĢtabli que les maladies vasculaires, ceĢreĢbrovasculaires et cardiovasculaires se manifestent diffeĢremment chez les hommes que chez les femmes. La rigiditeĢ arteĢrielle (RA), un preĢdicteur indeĢpendant de la maladie cardiovasculaire (MCV), a eĢteĢ associeĢe aĢ€ des changements de la reĢactiviteĢ ceĢreĢbrovasculaire (RCV) et aĢ€ un deĢclin cognitif lors du vieillissement. Plus preĢciseĢment, les personnes aĢ‚geĢes ayant une RA plus eĢleveĢe preĢsentent un deĢclin plus marqueĢ au niveau des taĢ‚ches exeĢcutives. Une diminution des fonctions exeĢcutives (FE) est eĢgalement lieĢe aĢ€ une reĢduction de la RCV chez les personnes aĢ‚geĢes. Cependant, il est important de noter que la relation entre la RA et la RCV est plus complexe. Certaines eĢtudes montrent une diminution de la RCV associeĢe avec une RA plus eĢleveĢe, tandis que dā€™autres rapportent une RCV preĢserveĢe avec une RA eĢleveĢe. De plus, des travaux reĢcents suggeĢ€rent que les diffeĢrences de concentration en heĢmatocrit (HCT) pourraient avoir une incidence sur les mesures de RA. Ici, nous avons eĢtudieĢ le roĢ‚le possible du sexe et de l'HCT sur ces relations heĢmodynamiques. MeĢthodes: Des acquisitions ont eĢteĢ effectueĢes chez 48 adultes aĢ‚geĢs en bonne santeĢ (31 femmes, 63 Ā± 5 ans) dans un scanneur dā€™imagerie par reĢsonance magneĢtique (IRM) 3T. Des donneĢes de marquage de spin arteĢriel pseudo-continu utilisant des lectures aĢ€ double eĢcho ont eĢteĢ collecteĢes pendant un deĢfi d'hypercapnie (changement de CO2 de 5mmHg, pendant deux blocs de 2 minutes). La RCV a eĢteĢ calculeĢe comme eĢtant le % de changement du signal de deĢbit sanguin ceĢreĢbral (% āˆ†CBF) par changement de mmHg dans le CO2 aĢ€ la fin de lā€™expiration. Les donneĢes de vitesse dā€™onde de pouls (VOP) aortique ont eĢteĢ acquises aĢ€ lā€™aide dā€™une seĢrie de contraste de phase cine encodeĢe par la vitesse durant 60 phases cardiaques avec un encodage en veĢlociteĢ de 180cm/s dans le plan. La VOP dans l'arcade aortique a eĢteĢ calculeĢe entre l'aorte ascendante et descendante. Les analyses statistiques ont eĢteĢ effectueĢes aĢ€ l'aide de SPSS. ReĢsultats: Un test de modeĢration controĢ‚lant pour lā€™aĢ‚ge et le volume des hyperintensiteĢs de la matieĢ€re blanche a reĢveĢleĢ un effet direct significatif de la VOP sur la RCV (Ī² = 1,630, IC aĢ€ 95% [.654, 2,607), ainsi que de la VOP sur la FE (Ī² = -. 998, IC 95% [-1,697, -,299]). Le sexe a modeĢreĢ la relation entre VOP et RCV (Ī² = -1,013, IC 95% [-1,610, -,4169]), et VOP et FE (Ī² = .447, IC 95% [.020, .875]). En outre, il existait un effet significatif de lā€™HCT sur les diffeĢrences de sexe observeĢes dans lā€™effet de modeĢration (VOP * SEXE) sur la FE (Ī² = -0,7680, SE = 0,3639, IC 95% [-1,5047, -0,0314], p = 0,0414). Conclusion: Nos reĢsultats indiquent que les relations entre la VOP, la RCV et la FE sont complexes et que le sexe et lā€™HCT modulentces relations. Lā€™influence des variations hormonales (p. ex. la meĢnopause) sur ces relations devrait eĢ‚tre eĢtudieĢe dans le futur et pourrait permettre de personnaliser les strateĢgies de preĢvention des MCV.Introduction: It is well established that sex differences exist in the manifestation of vascular, cerebrovascular and cardiovascular disease. Arterial stiffness (AS), an independent predictor of cardiovascular disease (CVD), has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a steeper decline on executive function (EF) tasks. Decreased EF is also linked with reduction in CVR among older adults. Interestingly, the relationship between AS and CVR is more complex, where some works show decreased CVR with increased AS, and others demonstrate preserved CVR with higher AS. In addition, recent work suggests that measurements of AS may be affected by differences in the concentration of hematocrit (HCT). Here, we investigated the possible role of sex and HCT on these hemodynamic relationships. Methods: Acquisitions were completed in 48 healthy older adults (31 females, 63 Ā± 5 years) on a 3T MRI. Pseudo-continuous arterial spin labeling using dual-echo readouts were collected during a hypercapnia challenge (5mmHg CO2 change, during two, 2 min blocks). CVR was calculated as the %āˆ†CBF signal per mmHg change in end-tidal CO2. Aortic PWV data was acquired using a cine phase contrast velocity encoded series during 60 cardiac phases with a velocity encoding of 180cm/s through plane. PWV in the aortic arch was computed between ascending and descending aorta. Statistical analyses were done using SPSS. Results: A moderation model test controlling for age and white matter hyperintensity volume revealed a significant direct effect of PWV on CVR (Ī²=1.630, 95% CI [.654, 2.607), as well as PWV on EF (Ī²=-.998, 95% CI [-1.697, -.299]). Sex moderated the relationship between PWV and CVR (Ī²=-1.013, 95% CI [-1.610, -.4169]), and PWV and EF (Ī²=.447, 95% CI [.020, .875]). In addition, there was a significant effect of HCT on the sex differences observed in the moderation effect (PWV*SEX) on EF (Ī²=-0.7680, SE = 0.3639 ,95% CI [-1.5047, -0.0314], p=0.0414). Conclusion: Together, our results indicate that the relationships between PWV, CVR and EF is complex and in part mediated by sex and HCT. Future work should investigate the role of hormone variations (e.g., menopause) on these relationships to better personalize CVD prevention strategies

    The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity

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    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 Ī”%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Ī”%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

    Assessment of the effects of aerobic fitness on cerebrovascular function in young adults using multiple inversion time arterial spin labelling MRI

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    The cross-sectional study investigated the effects of aerobic fitness on cerebrovascular function in the healthy brain. We quantified grey matter (GM) cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), in a sample of young adults within a normal fitness range. Based on existing TCD and fMRI evidence, we predicted a positive relationship between fitness and resting GM CBF, and CVR. Exploratory hypotheses that highe

    Modeling of dynamic cerebrovascular reactivity to spontaneous and externally induced CO2 fluctuations in the human brain using BOLD-fMRI

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    In this work, we investigate the regional characteristics of the dynamic interactions between arterial CO2 and BOLD (dynamic cerebrovascular reactivity - dCVR) during normal breathing and hypercapnic, externally induced step CO2 challenges. To obtain dCVR curves at each voxel, we use a custom set of basis functions based on the Laguerre and gamma basis sets. This allows us to obtain robust dCVR estimates both in larger regions of interest (ROIs), as well as in individual voxels. We also implement classification schemes to identify brain regions with similar dCVR characteristics. Our results reveal considerable variability of dCVR across different brain regions, as well as during different experimental conditions (normal breathing and hypercapnic challenges), suggesting a differential response of cerebral vasculature to spontaneous CO2 fluctuations and larger, externally induced CO2 changes that are possibly associated with the underlying differences in mean arterial CO2 levels. The clustering results suggest that anatomically distinct brain regions are characterized by different dCVR curves that in some cases do not exhibit the standard, positive valued curves that have been previously reported. They also reveal a consistent set of dCVR cluster shapes for resting and forcing conditions, which exhibit different distribution patterns across brain voxels
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