Cerebrovascular reactivity in the brain white matter: magnitude, temporal characteristics, and age effects.
Ontology highlight
ABSTRACT:
SUBMITTER: Thomas BP
PROVIDER: S-EPMC3915204 | biostudies-other | 2014 Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:ObjectiveTo compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR).MethodsSeventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons.ResultsAreas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p < 0.01), compared to areas with positive CVR.ConclusionsImpaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease.
| S-EPMC5135028 | biostudies-literature
Project description:AimsThis study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline.MethodsA total of 233 WMH subjects were recruited and categorized into WMH-I (n = 106), WMH-II (n = 72), and WMH-III (n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored.ResultsSubjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = -0.1248, 95% CI: -0.4689, -0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = -0.1436, 95% CI: -0.4584, -0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG.ConclusionThe CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals.
| S-EPMC8930816 | biostudies-literature
Project description:ObjectiveAdvanced paternal age is associated with poor offspring developmental outcome. Though an increase in paternal age-related germline mutations may affect offspring white matter development, outcome differences could also be due to psychosocial factors. Here we investigate possible cerebral changes prior to strong environmental influences using brain MRI in a cohort of healthy term-born neonates.MethodsWe used structural and diffusion MRI images acquired soon after birth from a cohort (n = 275) of healthy term-born neonates. Images were analysed using a customised tract based spatial statistics (TBSS) processing pipeline. Neurodevelopmental assessment using the Bayley-III scales was offered to all participants at age 18 months. For statistical analysis neonates were compared in two groups, representing the upper quartile (paternal age ≥38 years) and lower three quartiles. The same method was used to assess associations with maternal age.ResultsIn infants with older fathers (≥38 years), fractional anisotropy, a marker of white matter organisation, was significantly reduced in three early maturing anatomical locations (the corticospinal tract, the corpus callosum, and the optic radiation). Fractional anisotropy in these locations correlated positively with Bayley-III cognitive composite score at 18 months in the advanced paternal age group. A small but significant reduction in total brain volume was also observed in in the infants of older fathers. No significant associations were found between advanced maternal age and neonatal imaging.ConclusionsThe epidemiological association between advanced paternal age and offspring outcome is extremely robust. We have for the first time demonstrated a neuroimaging phenotype of advanced paternal age before sustained parental interaction that correlates with later outcome.
| S-EPMC7284122 | biostudies-literature
Project description:There has been little change in morbidity and mortality in traumatic brain injury (TBI) in the last 25 years. However, literature has emerged linking impaired cerebrovascular reactivity (a surrogate of cerebral autoregulation) with poor outcomes post-injury. Thus, cerebrovascular reactivity (derived through the pressure reactivity index; PRx) is emerging as an important continuous measure. Furthermore, recent literature indicates that autonomic dysfunction may drive impaired cerebrovascular reactivity in moderate/severe TBI. Thus, to improve our understanding of this association, we assessed the physiological relationship between PRx and the autonomic variables of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) using time-series statistical methodologies. These methodologies include vector autoregressive integrative moving average (VARIMA) impulse response function analysis, Granger causality, and hierarchical clustering. Granger causality testing displayed inconclusive results, where PRx and the autonomic variables had varying bidirectional relationships. Evaluating the temporal profile of the impulse response function plots demonstrated that the autonomic variables of BRS, ratio of low/high frequency of HRV and very low frequency HRV all had a strong relation to PRx, indicating that the sympathetic autonomic response may be more closely linked to cerebrovascular reactivity, then other variables. Finally, BRS was consistently associated with PRx, possibly demonstrating a deeper relationship to PRx than other autonomic measures. Taken together, cerebrovascular reactivity and autonomic response are interlinked, with a bidirectional impact between cerebrovascular reactivity and circulatory autonomics. However, this work is exploratory and preliminary, with further study required to extract and confirm any underlying relationships.
| S-EPMC10013014 | biostudies-literature
Project description:Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon whereby brief ischemic exposure confers tolerance to a subsequent ischemic challenge. IPC has not been studied selectively in CNS white matter (WM), although stroke frequently involves WM. We determined whether IPC is present in WM and, if so, its mechanism. We delivered a brief in vivo preconditioning ischemic insult (unilateral common carotid artery ligation) to 12- to 14-week-old mice and determined WM ischemic vulnerability [oxygen-glucose deprivation (OGD)] 72 h later, using acutely isolated optic nerves (CNS WM tracts) from the preconditioned (ipsilateral) and control (contralateral) hemispheres. Functional and structural recovery was assessed by quantitative measurement of compound action potentials (CAPs) and immunofluorescent microscopy. Preconditioned mouse optic nerves (MONs) showed better functional recovery after OGD than the non-preconditioned MONs (31 ± 3 vs 17 ± 3% normalized CAP area, p < 0.01). Preconditioned MONs also showed improved axon integrity and reduced oligodendrocyte injury compared with non-preconditioned MONs. Toll-like receptor-4 (TLR4) and type 1 interferon receptor (IFNAR1), key receptors in innate immune response, are implicated in gray matter preconditioning. Strikingly, IPC-mediated WM protection was abolished in both TLR4(-/-) and IFNAR1(-/-) mice. In addition, IPC-mediated protection in WM was also abolished in IFNAR1(fl/fl) LysM(cre), but not in IFNAR1(fl/fl) control, mice. These findings demonstrated for the first time that IPC was robust in WM, the phenomenon being intrinsic to WM itself. Furthermore, WM IPC was dependent on innate immune cell signaling pathways. Finally, these data demonstrated that microglial-specific expression of IFNAR1 plays an indispensable role in WM IPC.Significance statementIschemic preconditioning (IPC) has been studied predominantly in gray matter, but stroke in humans frequently involves white matter (WM) as well. Here we describe a novel, combined in vivo/ex vivo mouse model to determine whether IPC occurs in WM. It does. Using genetically altered mice, we identified two innate immune cell receptors, Toll-like receptor 4 and type 1 interferon receptor (IFNAR1), that are required for IPC-mediated protection in WM. Furthermore, using microglia-targeted IFNAR1 knockdown, we demonstrate that interferon signaling specifically in microglia is essential for this protection. The discovery of IPC as an intrinsic capability of WM is novel and important. This is also the first in vivo demonstration that cell-type-specific expression of an individual gene plays an indispensable role in IPC-mediated protection.
| S-EPMC4659824 | biostudies-literature
Project description:A fundamental, yet rarely tested premise of developmental cognitive neuroscience is that changes in brain activity and improvements in behavioral control across adolescent development are related to brain maturational factors that shape a more efficient, highly-interconnected brain in adulthood. We present the first multimodal neuroimaging study to empirically demonstrate that maturation of executive cognitive ability is directly associated with the relationship of white matter development and age-related changes in neural network functional integration. In this study, we identified specific white matter regions whose maturation across adolescence appears to reduce reliance on local processing in brain regions recruited for conscious, deliberate cognitive control in favor of a more widely distributed profile of functionally-integrated brain activity. Greater white matter coherence with age was associated with both increases and decreases in functional connectivity within task-engaged functional circuits. Importantly, these associations between white matter development and brain system functional integration were related to behavioral performance on tests of response inhibition, demonstrating their importance in the maturation of optimal cognitive control.
| S-EPMC2753497 | biostudies-literature
Project description:ObjectiveTo 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 designDecomposition 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 observationsWe 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.ConclusionDecomposition and novel iterative modeling of different temporal components of the dynamic CO 2-BOLD relationship improves quantitative CVR measurements.
| S-EPMC5607533 | biostudies-literature
Project description:Background: Current imaging-based discrimination between radiation necrosis versus recurrent glioblastoma contrast-enhancing lesions remains imprecise but is paramount for prognostic and therapeutic evaluation. We examined whether patients with radiation necrosis exhibit distinct patterns of blood oxygenation-level dependent fMRI cerebrovascular reactivity (BOLD-CVR) as the first step to better distinguishing patients with radiation necrosis from recurrent glioblastoma compared with patients with newly diagnosed glioblastoma before surgery and radiotherapy. Methods: Eight consecutive patients with primary and secondary brain tumors and a multidisciplinary clinical and radiological diagnosis of radiation necrosis, and fourteen patients with a first diagnosis of glioblastoma underwent BOLD-CVR mapping. For all these patients, the contrast-enhancing lesion was derived from high-resolution T1-weighted MRI and rendered the volume-of-interest (VOI). From this primary VOI, additional 3 mm concentric expanding VOIs up to 30 mm were created for a detailed perilesional BOLD-CVR tissue analysis between the two groups. Receiver operating characteristic curves assessed the discriminative properties of BOLD-CVR for both groups. Results: Mean intralesional BOLD-CVR values were markedly lower in radiation necrosis than in glioblastoma contrast-enhancing lesions (0.001 ± 0.06 vs. 0.057 ± 0.05; p = 0.04). Perilesionally, a characteristic BOLD-CVR pattern was observed for radiation necrosis and glioblastoma patients, with an improvement of BOLD-CVR values in the radiation necrosis group and persisting lower perilesional BOLD-CVR values in glioblastoma patients. The ROC analysis discriminated against both groups when these two parameters were analyzed together (area under the curve: 0.85, 95% CI: 0.65-1.00). Conclusions: In this preliminary analysis, distinctive intralesional and perilesional BOLD-cerebrovascular reactivity patterns are found for radiation necrosis.
| S-EPMC8069508 | biostudies-literature
Project description:White matter abnormalities, related to poor cerebral perfusion, are a core feature of small vessel cerebrovascular disease, and critical determinants of vascular cognitive impairment and dementia. Despite this importance there is a lack of treatment options. Proliferation of microglia producing an expanded, reactive population and associated neuroinflammatory alterations have been implicated in the onset and progression of cerebrovascular white matter disease, in patients and in animal models, suggesting that targeting microglial proliferation may exert protection. Colony-stimulating factor-1 receptor (CSF1R) is a key regulator of microglial proliferation. We found that the expression of CSF1R/Csf1r and other markers indicative of increased microglial abundance are significantly elevated in damaged white matter in human cerebrovascular disease and in a clinically relevant mouse model of chronic cerebral hypoperfusion and vascular cognitive impairment. Using the mouse model, we investigated long-term pharmacological CSF1R inhibition, via GW2580, and demonstrated that the expansion of microglial numbers in chronic hypoperfused white matter is prevented. Transcriptomic analysis of hypoperfused white matter tissue showed enrichment of microglial and inflammatory gene sets, including phagocytic genes that were the predominant expression modules modified by CSF1R inhibition. Further, CSF1R inhibition attenuated hypoperfusion-induced white matter pathology and rescued spatial learning impairments and to a lesser extent cognitive flexibility. Overall, this work suggests that inhibition of CSF1R and microglial proliferation mediates protection against chronic cerebrovascular white matter pathology and cognitive deficits. Our study nominates CSF1R as a target for the treatment of vascular cognitive disorders with broader implications for treatment of other chronic white matter diseases.
| S-EPMC10952452 | biostudies-literature
Project description:White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.
| S-EPMC3915198 | biostudies-literature