The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

Co-existing intracranial and extracranial carotid atherosclerosis predicts large-artery atherosclerosis stroke recurrence: a single-center prospective study utilizing combined head-and-neck vessel wall imaging.

OBJECTIVES: Intracranial and extracranial plaque features on high-resolution vessel wall imaging (HR-VWI) are associated with large-artery atherosclerosis (LAA) stroke recurrence. However, most studies have focused on a single vascular bed, and the prognostic value of combined intracranial and extracranial plaque features has yet to be studied. This study aimed to investigate the roles of plaque features, plaque number, and co-existing atherosclerosis in predicting stroke recurrence, utilizing combined head-and-neck HR-VWI. METHODS: From September 2016 to March 2020, participants with acute LAA ischemic strokes were prospectively enrolled and underwent combined head-and-neck HR-VWI. The participants were followed for stroke recurrence for at least 12 months or until a subsequent event occurred. The imaging features at baseline, including conventional and histogram plaque features, plaque number, and co-existing atherosclerosis, were evaluated. Univariable Cox regression analysis and the least absolute shrinkage and selection operator (lasso) method were used for variable screening. Multivariable Cox regression analyses were used to determine the independent risk factors of stroke recurrence. RESULTS: A total of 97 participants (59 ± 12 years, 63 men) were followed for a median of 30.9 months, and 21 participants experienced recurrent strokes. Multivariable Cox analysis identified co-existing intracranial high signal on T1-weighted fat-suppressed images (HST1) and extracranial carotid atherosclerosis (HR, 6.12; 95% CI, 2.52-14.82; p = 0.001) as an independent imaging predictor of stroke recurrence. CONCLUSION: Co-existing intracranial HST1 and extracranial carotid atherosclerosis independently predicted LAA stroke recurrence. Combined head-and-neck HR-VWI is a promising technique for atherosclerosis imaging. CLINICAL RELEVANCE STATEMENT: This prospective study using combined head-and-neck HR-VWI highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. KEY POINTS: • This study highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. • This prospective study using combined head-and-neck HR-VWI found co-existing intracranial HST1 and extracranial carotid atherosclerosis to be independent predictors of stroke recurrence.

Cerebral blood flow regulates iron overload in the cerebral nuclei of hemodialysis patients with anemia.

Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia.