Multiparametric and multilevel characterization of morphological alterations in patients with transient ischemic attack.

Transient ischemic attack (TIA), an important risk factor for stroke, is associated with widespread disruptions of functional brain architecture. However, TIA-related structural alterations are not well established. By analyzing structural MRI data from 50 TIA patients versus 40 healthy controls (HCs), here we systematically investigated TIA-related morphological alterations in multiple cortical surface-based indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]) at multiple levels (local topography, interregional connectivity and whole-brain network topology). For the observed alterations, their associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers were further examined. We found that compared with the HCs, the TIA patients showed widespread morphological alterations and the alterations depended on choices of morphological index and analytical level. Specifically, the patients exhibited: (a) regional CT decreases in the transverse temporal gyrus and lateral sulcus; (b) impaired FD- and GI-based connectivity mainly involving visual, somatomotor and ventral attention networks and interhemispheric connections; and (c) altered GI-based whole-brain network efficiency and decreased FD-based nodal centrality in the middle frontal gyrus. Moreover, the impaired morphological connectivity showed high sensitivities and specificities for distinguishing the patients from HCs. Altogether, these findings demonstrate the emergence of morphological index-dependent and analytical level-specific alterations in TIA, which provide novel insights into neurobiological mechanisms underlying TIA and may serve as potential biomarkers to help diagnosis of the disease. Meanwhile, our findings highlight the necessity of using multiparametric and multilevel approaches for a complete mapping of cerebral morphology in health and disease.

Toward neuroimaging-based network biomarkers for transient ischemic attack.

Stroke is associated with topological disruptions of large-scale functional brain networks. However, whether these disruptions occur in transient ischemic attack (TIA), an important risk factor for stroke, remains largely unknown. Combining multimodal MRI techniques, we systematically examined TIA-related topological alterations of functional brain networks, and tested their reproducibility, structural, and metabolic substrates, associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers. We found that functional networks in patients with TIA exhibited decreased whole-brain network efficiency, reduced nodal centralities in the bilateral insula and basal ganglia, and impaired connectivity of inter-hemispheric communication. These alterations remained largely unchanged when using different brain parcellation schemes or correcting for micro head motion or for regional gray matter volume, cerebral blood flow or hemodynamic lag of BOLD signals in the patients. Moreover, some alterations correlated with the levels of high-density lipoprotein cholesterol (an index related to ischemic attacks via modulation of atherosclerosis) in the patients, distinguished the patients from healthy individuals, and predicted future ischemic attacks in the patients. Collectively, these findings highlight the emergence of characteristic network dysfunctions in TIA, which may aid in elucidating pathological mechanisms and establishing diagnostic and prognostic biomarkers for the disease.

Altered Functional Connectivity within Default Mode Network in Patients with Transient Ischemic Attack: A Resting-State Functional Magnetic Resonance Imaging Study.

Default mode network (DMN) is an important functional brain network that supports aspects of cognition. Stroke has been reported to be associated with functional connectivity (FC) impairments within DMN. However, whether FC within DMN changes in transient ischemic attack (TIA), an important risk factor for stroke, remains unclear. Forty-eight TIA patients and 41 age- and sex-matched healthy controls (HCs) were recruited in this study. Using resting-state functional magnetic resonance imaging seed-based FC methods, we examined FC alterations within DMN in TIA patients, tested its associations with clinical information, and further explored the ability of FC abnormalities to predict follow-up ischemic attacks. We found significantly decreased FC of left middle temporal gyrus/angular gyrus both with medial prefrontal cortex (mPFC) and posterior cingulate cortex/precuneus (PCC/Pcu) and significantly decreased FC among each pair of mPFC, left PCC, and right Pcu in patients with TIA as compared with HCs. Moreover, the connectivity between mPFC and left PCC could predict future ischemic attacks of the patients. Collectively, these findings may provide insights into further understanding of the underlying pathological mechanism in TIA, and aberrant FC between the hubs within DMN may provide a reference for the imaging diagnosis and early intervention of TIA.

Serum Soluble Corin is Decreased in Stroke.

BACKGROUND AND PURPOSE: Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS: Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS: Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS: Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.

Non-invasive evaluation of cerebral perfusion in patients with transient ischemic attack: an fMRI study.

Detection of hypoperfused tissue due to the ischemia is considered to be important in understanding the cerebral perfusion status and may be helpful in guiding therapeutic decisions for patients with transient ischemic attack (TIA). We hypothesized that the combination of two non-invasive fMRI techniques: resting-state BOLD-fMRI time-shift analysis (TSA) approach and 3D ASL, could detect the cerebral hemodynamic status in TIA patients noninvasively. From April 2015 to June 2016, 51 TIA patients were recruited in this study. We calculated the time delay between the resting-state BOLD signal at each voxel and the whole-brain signal using TSA approach and compared the results to CBF map derived from ASL. Out of the 51 patients, 24 patients with normal arrival time and CBF were in Stage 0; 14 patients who showed delayed arrival time and normal CBF which indicated elevated CBV were in Stage I; the other 13 patients who had both delayed arrival time and decreased CBF were in Stage II, the group average spatial overlap, i.e., Dice coefficient, of the two measurements was 0.55. Four patients in Stage 0 (17.4%), three patients in Stage I (23.1%) and five patients in Stage II (45.5%) suffered ischemic stroke or TIA symptoms in 1 year after MRI scan. The patients in Stage II was at highest risk of subsequent events when compared to other two stages. The combination of resting-state BOLD-fMRI and ASL hold the potential to noninvasively identify the hemodynamic status in TIA patients and help predict the risk of subsequent events.

The Local Brain Abnormalities in Patients With Transient Ischemic Attack: A Resting-State fMRI Study.

Background: Transient ischemic attack (TIA) is an important risk factor for stroke. Despite the transient episodes of clinical symptoms, brain alterations are still observed in patients with TIA. However, the functional mechanism of transient ischemia is still unclear. Here, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to explore the functional abnormalities in patients with TIA. Methods: 48 TIA patients and 41 age- and sex-matched healthy controls (HCs) were enrolled in the study. For each participant, we collected rs-fMRI data and clinical/physiological/biochemical data. Amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were then calculated. Two sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Furthermore, a correlation analysis was performed to explore the relationship between local brain abnormalities and clinical/physiological/biochemical characteristics tests in TIA patients. Results: Compared with the HCs, the TIA patients exhibited decreased ALFF in the left middle temporal gyrus, decreased DC in the triangular part of right inferior frontal gyrus, and no significant statistical difference in ReHo. No correlation was found between local abnormalities and clinical/physiological/biochemical scores in the patients with TIA. Conclusion: Collectively, we found decreased ALFF and DC in patients with TIA which provide evidence for local brain dysfunctions and may help to understand the pathological mechanism for the disease.

Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke.

OBJECTIVE: Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS: We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS: Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION: Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis.