On the assessment of cerebrovascular reactivity using hypercapnia BOLD MRI.
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ABSTRACT:
SUBMITTER: Yezhuvath US
PROVIDER: S-EPMC2726998 | biostudies-other | 2009 Aug
REPOSITORIES: biostudies-other
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Project description:PurposeTo develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice.MethodsWe described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated.ResultsCerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p = 0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p = 0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6 months after the study without noticeable aberrant behavior or appearance.ConclusionsWe demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.
| S-EPMC9574885 | biostudies-literature
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.
| S-EPMC6811507 | biostudies-literature
Project description:In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO2) modulations, in units of [%?BOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO2-based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p?0.1). In contrast, for the more qualitative CVR measures, significant within-subject association with qCVR was only achieved in 50-70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously.
| S-EPMC5148619 | biostudies-literature
Project description:BackgroundObstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk.PurposeTo investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects.Study typeProspective.SubjectsTwenty-six SCD patients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemic patients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%).Field strength/sequence3T, gradient-echo echo-planar imaging.AssessmentA transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR).Statistical testsUnivariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups.ResultsCompared to controls, SCD and chronically anemic patients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline).Data conclusionTransient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.
| S-EPMC7655661 | biostudies-literature
Project description:Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories.Patients (n?=?12; age?=?55 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported.BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P???0.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P?>?0.003) or across territories (P?>?0.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease.Dual echo VE-ASL can provide simultaneous cerebral blood flow and qualitative BOLD contrast consistent with lateralizing disease severity in patients with asymmetric steno-occlusive disease. The methodological strengths and limitations of composite BOLD and VE-ASL measurements in the clinic are discussed.
| S-EPMC4435663 | biostudies-literature
Project description:Cerebrovascular reactivity (CVR) is defined as the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. We used changes in blood oxygenation level-dependent (BOLD) MRI as surrogates for changes of CBF, and standardized quantitative changes in arterial partial pressure of carbon dioxide as the stimulus. Despite uniform stimulus and test conditions, differences in voxel-wise BOLD changes between testing sites may remain, attributable to physiologic and machine variability. We generated a reference atlas of normal CVR metrics (voxel-wise mean and SD) for each of two sites. We hypothesized that there would be no significant differences in CVR between the two atlases enabling each atlas to be used at any site. A total of 69 healthy subjects were tested to create site-specific atlases, with 20 of those individuals tested at both sites. 38 subjects were scanned at Site 1 (17F, 37.5 ± 16.8 y) and 51 subjects were tested at Site 2 (22F, 40.9 ± 17.4 y). MRI platforms were: Site 1, 3T Magnetom Skyra Siemens scanner with 20-channel head and neck coil; and Site 2, 3T HDx Signa GE scanner with 8-channel head coil. To construct the atlases, test results of individual subjects were co-registered into a standard space and voxel-wise mean and SD CVR metrics were calculated. Map comparisons of z scores found no significant differences between white matter or gray matter in the 20 subjects scanned at both sites when analyzed with either atlas. We conclude that individual CVR testing, and atlas generation are compatible across sites provided that standardized respiratory stimuli and BOLD MRI scan parameters are used. This enables the use of a single atlas to score the normality of CVR metrics across multiple sites.
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Project description:Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12-18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO2 regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.
| S-EPMC7820694 | biostudies-literature
Project description:Cerebrovascular reactivity (CVR) reflects the CBF change to meet different physiological demands. The reference CVR technique is PET imaging with vasodilators but is inaccessible to most patients. DSC can measure transit time to evaluate patients suspected of stroke, but the use of gadolinium may cause side-effects. Arterial spin labeling (ASL) is a non-invasive MRI technique for CBF measurements. Here, we investigate the effectiveness of ASL with single and multiple post labeling delays (PLD) to replace PET and DSC for CVR and transit time mapping in 26 Moyamoya patients. Images were collected using simultaneous PET/MRI with acetazolamide. CVR, CBF, arterial transit time (ATT), and time-to-maximum (Tmax) were measured in different flow territories. Results showed that CVR was lower in occluded regions than normal regions (by 68 ± 12%, 52 ± 5%, and 56 ± 9%, for PET, single- and multi-PLD PCASL, respectively, all p < 0.05). Multi-PLD PCASL correlated slightly higher with PET (CCC = 0.36 and 0.32 in affected and unaffected territories respectively). Vasodilation caused ATT to reduce by 4.5 ± 3.1% (p < 0.01) in occluded regions. ATT correlated significantly with Tmax (R2 > 0.35, p < 0.01). Therefore, multi-PLD ASL is recommended for CVR studies due to its high agreement with the reference PET technique and the capability of measuring transit time.
| S-EPMC9274857 | biostudies-literature
Project description:Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54?±?0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N?=?39) revealed a similar correlation of 0.57?±?0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.
| S-EPMC6338507 | biostudies-literature
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.
| S-EPMC7292765 | biostudies-literature