Disrupted Topological Organization of Functional Networks in Asymptomatic Carotid Plaque Without Significant Carotid Stenosis: A Resting-State fMRI Study.
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ABSTRACT:
SUBMITTER: Tuo J
PROVIDER: S-EPMC8375554 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE This article describes the use of ultrasound measurements of physical strain within carotid atherosclerotic plaques as a measure of instability and the potential for vascular cognitive decline, microemboli, and white matter changes. METHODS Asymptomatic patients with significant (> 60%) carotid artery stenosis were studied for dynamic measures of plaque instability, presence of microemboli, white matter changes, and vascular cognitive decline in comparison with normative controls and premorbid state. RESULTS Although classically asymptomatic, these patients showed vascular cognitive decline. The degree of strain instability measured within the atherosclerotic plaque directly predicted vascular cognitive decline in these patients thought previously to be asymptomatic according to classic criteria. Furthermore, 26% of patients showed microemboli, and patients had twice as much white matter hyperintensity as controls. CONCLUSIONS These data show that physical measures of plaque instability are possible through interpretation of ultrasound strain data during pulsation, which may be more clinically relevant than solely measuring degree of stenosis. The data also highlight the importance of understanding that the definition of symptoms should not be limited to motor, speech, and vision function but underscore the role of vascular cognitive decline in the pathophysiology of carotid atherosclerotic disease. Clinical trial registration no.: NCT02476396 (clinicaltrials.gov).
| S-EPMC5592121 | biostudies-literature
Project description:Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.
| S-EPMC3866189 | biostudies-literature
Project description:To evaluate the cost-effectiveness of a decision-making rule based on the magnetic resonance (MR) imaging assessment of intraplaque hemorrhage (IPH) in patients with asymptomatic carotid artery stenosis.Two competing stroke prevention strategies were compared: (a) an intensive medical therapy-based management strategy versus (b) an imaging-based strategy in which the subset of patients with asymptomatic carotid artery stenosis with IPH on MR images would undergo immediate carotid endarterectomy in addition to ongoing intensive medical therapy. Patients in the medical therapy-only group could undergo carotid endarterectomy only with substantial carotid artery stenosis disease progression. Lifetime quality-adjusted life years (QALYs) and costs were modeled for patients with asymptomatic carotid artery stenosis with 70%-89% and 50%-69% carotid artery stenosis at presentation. Risks of stroke and complications from carotid endarterectomy, costs, and quality of life values were estimated from published sources.The medical therapy-based strategy had a lower life expectancy (12.65 years vs 12.95 years), lower lifetime QALYs (9.96 years vs 10.05 years), and lower lifetime costs ($13 699 vs $15 297) when compared with the MR imaging IPH-based strategy. The incremental cost-effectiveness ratio (ICER) for the MR imaging IPH strategy compared with the medical therapy-based strategy was $16 000 per QALY by using a base-case 70-year-old patient. When using starting patient ages of 60 and 80 years, the ICERs for the MR imaging IPH strategy were $3100 per QALY and $73 000 per QALY, respectively. The ICERs for the MR imaging IPH strategy were slightly higher at all ages for 50%-69% stenosis but remained below a willingness-to-pay threshold of $100 000 per QALY for starting ages of 60 and 70 years.MR imaging IPH can be used as a cost-effective tool to identify patients with asymptomatic carotid artery stenosis most likely to benefit from carotid endarterectomy.
| S-EPMC4672599 | biostudies-literature
Project description:Ultrasonographic plaque echolucency has been studied as a stroke risk marker in carotid atherosclerotic disease. We performed a systematic review and meta-analysis to summarize the association between ultrasound-determined carotid plaque echolucency and future ipsilateral stroke risk.We searched the medical literature for studies evaluating the association between carotid plaque echolucency and future stroke in asymptomatic patients. We included prospective observational studies with stroke outcome ascertainment after baseline carotid plaque echolucency assessment. We performed a meta-analysis and assessed study heterogeneity and publication bias. We also performed subgroup analyses limited to patients with stenosis ?50%, studies in which plaque echolucency was determined via subjective visual interpretation, studies with a relatively lower risk of bias, and studies published after the year 2000.We analyzed data from 7 studies on 7557 subjects with a mean follow-up of 37.2 months. We found a significant positive relationship between predominantly echolucent (compared with predominantly echogenic) plaques and the risk of future ipsilateral stroke across all stenosis severities (0% to 99%; relative risk, 2.31; 95% confidence interval, 1.58-3.39; P<0.001) and in subjects with ?50% stenosis (relative risk, 2.61; 95% confidence interval, 1.47-4.63; P=0.001). A statistically significant increased relative risk for future stroke was preserved in all additional subgroup analyses. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses.The presence of ultrasound-determined carotid plaque echolucency provides predictive information in asymptomatic carotid artery stenosis beyond luminal stenosis. However, the magnitude of the increased risk is not sufficient on its own to iden tify patients likely to benefit from surgical revascularization.
| S-EPMC4280234 | biostudies-literature
Project description:Background Imaging may play an important role in identifying high-risk plaques in patients who have carotid disease and who could benefit from surgical revascularization. We sought to evaluate the cost effectiveness of a decision-making rule based on the ultrasound imaging assessment of plaque echolucency in patients with asymptomatic carotid stenosis. Methods and Results We used a decision-analytic model to project lifetime quality-adjusted life years and costs for 5 stroke prevention strategies: (1) medical therapy only; (2) revascularization if both plaque echolucency and stenosis progression to >90% are present; (3) revascularization only if plaque echolucency is present; (4) revascularization only if stenosis progression >90% is present; or (5) either plaque echolucency or stenosis progression is present. Risks of clinical events, costs, and quality-of-life values were estimated based on published sources and the analysis was conducted from a healthcare system perspective for asymptomatic patients with 70% to 89% carotid stenosis at presentation. Patients who did not undergo revascularization had the highest stroke events (17.6%) and lowest life-years (8.45), while those who underwent revascularization on the basis of either presence of plaque echolucency on ultrasound or progression of carotid stenosis had the lowest stroke events (12.0%) and longest life-years (14.41). The either plaque echolucency or progression-based revascularization group had an incremental cost-effectiveness ratio of $110 000/quality-adjusted life years compared with the plaque echolucency-based strategy, which had an incremental cost-effectiveness ratio of $29 000/quality-adjusted life years compared with the joint echolucency and progression-based strategy. Conclusions Plaque echolucency on ultrasound can be a cost-effective tool to identify patients with asymptomatic carotid artery stenosis most likely to benefit from carotid endarterectomy.
| S-EPMC6898827 | biostudies-literature
Project description:Even clinically "asymptomatic" carotid stenosis is associated with multidomain cognitive impairment, gray matter (GM) atrophy, and silent lesion. However, the links between them remain unclear. Using structural MRI data, we examined GM asymmetry index (AI) and white matter hyperintensity (WMH) in 24 patients with severe asymptomatic carotid stenosis (SACS), 24 comorbidity-matched controls, and independent samples of 84 elderly controls and 22 young adults. As compared to controls, SACS patients showed worse verbal memories, higher WMH burden, and right-lateralized GM in posterior middle temporal and mouth-somatomotor regions. These clusters extended to pars triangularis, lateral temporal, and cerebellar regions, when compared with young adults. Further, a full-path of WMH burden (X), GM volume (atrophy, M1), AI (asymmetry, M2), and neuropsychological variables (Y) through a serial mediation model was analyzed. This analysis identified that left-dominated GM atrophy and right-lateralized asymmetry in the posterior middle temporal cortex mediated the relationship between WMH burden and recall memory in SACS patients. These results suggest that the unbalanced hemispheric atrophy in the posterior middle temporal cortex is crucial to mediating relationship between WMH burden and verbal recall memories, which may underlie accelerated aging and cognitive deterioration in patients with SACS and other vascular cognitive impairment.
| S-EPMC8559457 | biostudies-literature
Project description:Two positive randomized trials established carotid endarterectomy (CEA) as a superior treatment to medical management alone for the treatment of asymptomatic carotid artery stenosis. However, advances in medical therapy have led to an active and spirited debate about the best treatment for asymptomatic carotid stenosis. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST 2) trial aims to better define the best treatment for the average patient with severe asymptomatic carotid stenosis. Enrollment in the trial may be hampered by strong opinions on either side of the debate. It is important to realize that equipoise exists and that neither the old data on CEA nor the new data on optimal medical therapy provide a rigorous answer. The assumption that medical therapy has already been proven superior to revascularization procedures may hinder both enrollment in the trial and technical advancements in revascularization procedures.
| S-EPMC5440242 | biostudies-literature
Project description:"Asymptomatic" carotid artery stenosis (aCAS) patients usually have cognitive impairment in the domains of executive, psychomotor speed, and memory function. However, the pathophysiology of this impairment in aCAS patients is still unclear. In this study, amplitude of low-frequency fluctuation (ALFF) method was used based on resting-state blood oxygenation level dependent (BOLD) signals, to investigate local brain activity in 19 aCAS patients and 24 healthy controls, aimed to explore this pathophysiology mechanism. We analyzed this intrinsic activity in four individual frequency bands: Slow-2 (0.198-0.25 Hz), Slow-3 (0.073-0.198 Hz), Slow-4 (0.027-0.073 Hz), and Slow-5 (0.01-0.027 Hz). The aCAS-related ALFF changes were mainly distributed in (1) cortical midline structure, including bilateral dorsomedial prefrontal (dmPFC), cingulate cortex (CC) and precuneus (PCu); (2) hippocampus and its adjacent structures, including bilateral hippocampus, thalamus and medial temporal regions. We found these spatial patterns were frequency-dependent. Significant interaction between frequency and group was found distributed in left putamen, triangle part of inferior temporal and bilateral precentral/postcentral gyrus when Slow-4 and Slow-5 were considered. The delay recall ability of aCAS patient was significantly positive correlated to the mean ALFF in dmPFC within Slow-4 band and the mean ALFF in the bilateral hippocampus within Slow-3 band, respectively. We also found the Montreal Cognitive Assessme score of aCAS patient was significantly positive correlated to the mean ALFF in right fusiform and parahippocampus within Slow-3 band. Furthermore, we built the automatic diagnosis and prediction models based on support vector machine (SVM) and back propagation neural network (BPNN), respectively. Both two types of models could achieve relatively competent performance, which meant the frequency-dependent changes in ALFF could not only reveal the pathophysiology mechanism of cognitive impairment of aCAS, but also could be used as neuroimaging marker in the analysis of cognition impairment for aCAS patients.
| S-EPMC6021536 | biostudies-other
Project description:Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA. Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed. Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features. Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
| S-EPMC8651616 | biostudies-literature
Project description:ObjectiveWe have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV).MethodsStructural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients.ResultsOf the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively).ConclusionsInterhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.
| S-EPMC8209736 | biostudies-literature