Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion.

Quantifying cerebral microbleeds using quantitative susceptibility mapping from magnetization-prepared rapid gradient-echo.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r2: 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B0 of 3 T or higher with no additional time cost, when standard T2*-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

Differentiating calcifications from cerebral microbleeds using quantitative susceptibility mapping.

OBJECTIVES: To differentiate cerebral microbleeds (CMBs) and calcifications using quantitative susceptibility mapping (QSM). METHODS: CMBs were visualized and located using QSM from susceptibility-weighted imaging data collected on a 3-T MR scanner. Calcifications of the pineal gland and the choroid plexus were localized first using CT. All calcifications and CMBs were assessed using QSM to evaluate their magnetic susceptibility. The distribution of the magnetic susceptibility for the CMBs was determined and the CT attenuation was correlated with the mean magnetic susceptibility for the calcifications. RESULTS: A total of 232 hypointense foci were selected from the QSM data: 121 were CMBs and 111 were calcifications. The mean magnetic susceptibility was -214 ± 112 ppb for the calcifications and 392 ± 204 ppb for the CMBs. The minimum value of magnetic susceptibility was 75 ppb for all the CMBs and the maximum value was -52 ppb for all the calcifications. The calcifications were clearly differentiable from the CMBs from the sign alone (p < 0.001). The magnetic susceptibility for the CMBs was 299 ± 133 ppb in the lobar subcortical white matter and 499 ± 220 ppb for deep CMBs in the basal ganglia, thalamus, and brainstem. There was a significant difference in the susceptibility between these two regions (p < 0.001). CONCLUSION: The sign of the magnetic susceptibility was sufficient to differentiate calcifications and CMBs. The concentration of calcium or iron can be determined from the susceptibility value itself. The deep CMBs had higher susceptibility on average than lobar bleeds. CLINICAL RELEVANCE STATEMENT: This study's ability to differentiate between CMBs and calcifications using QSM could enhance diagnostic accuracy, guiding more precise treatment decisions for stroke or tumor patients. KEY POINTS: The sign of magnetic susceptibility is sufficient to differentiate calcifications and CMBs. QSM can successfully differentiate calcifications from microbleeds. The concentration of calcium or iron can be determined from the susceptibility value itself.

Cerebral Microbleeds in Different Brain Regions and Their Associations With the Digital Clock-Drawing Test: Secondary Analysis of the Framingham Heart Study.

BACKGROUND: Cerebral microbleeds (CMB) increase the risk for Alzheimer disease. Current neuroimaging methods that are used to detect CMB are costly and not always accessible. OBJECTIVE: This study aimed to explore whether the digital clock-drawing test (DCT) may provide a behavioral indicator of CMB. METHODS: In this study, we analyzed data from participants in the Framingham Heart Study offspring cohort who underwent both brain magnetic resonance imaging scans (Siemens 1.5T, Siemens Healthcare Private Limited; T2*-GRE weighted sequences) for CMB diagnosis and the DCT as a predictor. Additionally, paper-based clock-drawing tests were also collected during the DCT. Individuals with a history of dementia or stroke were excluded. Robust multivariable linear regression models were used to examine the association between DCT facet scores with CMB prevalence, adjusting for relevant covariates. Receiver operating characteristic (ROC) curve analyses were used to evaluate DCT facet scores as predictors of CMB prevalence. Sensitivity analyses were conducted by further including participants with stroke and dementia. RESULTS: The study sample consisted of 1020 (n=585, 57.35% female) individuals aged 45 years and older (mean 72, SD 7.9 years). Among them, 64 (6.27%) participants exhibited CMB, comprising 46 with lobar-only, 11 with deep-only, and 7 with mixed (lobar+deep) CMB. Individuals with CMB tended to be older and had a higher prevalence of mild cognitive impairment and higher white matter hyperintensities compared to those without CMB (P<.05). While CMB were not associated with the paper-based clock-drawing test, participants with CMB had a lower overall DCT score (CMB: mean 68, SD 23 vs non-CMB: mean 76, SD 20; P=.009) in the univariate comparison. In the robust multiple regression model adjusted for covariates, deep CMB were significantly associated with lower scores on the drawing efficiency (ß=-0.65, 95% CI -1.15 to -0.15; P=.01) and simple motor (ß=-0.86, 95% CI -1.43 to -0.30; P=.003) domains of the command DCT. In the ROC curve analysis, DCT facets discriminated between no CMB and the CMB subtypes. The area under the ROC curve was 0.76 (95% CI 0.69-0.83) for lobar CMB, 0.88 (95% CI 0.78-0.98) for deep CMB, and 0.98 (95% CI 0.96-1.00) for mixed CMB, where the area under the ROC curve value nearing 1 indicated an accurate model. CONCLUSIONS: The study indicates a significant association between CMB, especially deep and mixed types, and reduced performance in drawing efficiency and motor skills as assessed by the DCT. This highlights the potential of the DCT for early detection of CMB and their subtypes, providing a reliable alternative for cognitive assessment and making it a valuable tool for primary care screening before neuroimaging referral.

Prevalence and associated factors of cerebral microbleeds in a rural population of the United States.

OBJECTIVE: Cerebral microbleeds (CMBs) can carry an advanced risk for the development and burden of cerebrovascular and cognitive disorders. Large-scale population-based studies are required to identify the at-risk population. METHOD: Ten percent (N = 3,056) of the Geisinger DiscovEHR Initiative Cohort participants who had brain magnetic resonance imaging (MRI) for any indication were randomly selected. Patients with CMBs were compared to an age-, gender-, body mass index-, and hypertension-matched cohort of patients without CMB. The prevalence of comorbidities and use of anticoagulation therapy was investigated in association with CMB presence (binary logistic regression), quantity (ordinal regression), and topography (multinomial regression). RESULTS: Among 3,056 selected participants, 477 (15.6 %) had CMBs in their MRI. Patients with CMBs were older and were more prevalently hypertensive, with ischemic stroke, arrhythmia, dyslipidemia, coronary artery disease, and the use of warfarin. After propensity-score matching, 477 patients with CMBs and 974 without were included for further analyses. Predictors of ≥5 CMBs were ischemic stroke (OR, 1.6; 95 % CI, 1.2 -2.0), peripheral vascular disease (OR, 1.6; 95 % CI, 1.1-2.3), and thrombocytopenia (OR, 1.9; 95 % CI, 1.2-2.9). Ischemic stroke was associated with strictly lobar CMBs more strongly than deep/infra-tentorial CMBs (OR, 2.1; 95 % CI, 1.5-3.1; vs. OR, 1.4; CI, 1.1-1.8). CONCLUSIONS: CMBs were prevalent in our white population. Old age, hypertension, anticoagulant treatment, thrombocytopenia, and a history of vascular diseases including stroke, were associated with CMBs.

Clinical, neuroimaging, and behavioural risk factors for neurocognitive impairment in Chinese patients with haemophilia: A multicentre study.

BACKGROUND: Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia. OBJECTIVES: To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors. METHODS: We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment. RESULTS: Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92-15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52-13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10-0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19-0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037). CONCLUSION: A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.

Association between Anatomical Variations of the Circle of Willis and Covert Vascular Brain Injury in the General Population.

BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.

Impact of Cerebral Microbleeds on Gait, Balance, and Upper Extremities Function in Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: White matter hyperintensites (WMHs) , lacunes and brain atrophy have been demonstrated to be positively related to gait disorder. However, cerebral microbleeds (CMBs) as a manifestation of cerebral small vessel disease (CSVD) is still under-investigated. Therefore, correlations between CMBs and upper extremity, gait and balance performance were investigated in this study. METHODS: A cross-sectional study of middle-aged to older adults was conducted. CSVD burden was measured with magnetic resonance imaging (MRI) and the location and number of CMBs were analysed. Gait and balance functions were evaluated using a four meter walkway, Tinetti, Timed-Up-and-Go (TUG) and Short Physical Performance Battery (SPPB) tests. Upper extremity function was measured by 10 repeated pronation-supination time, 10 repeated finger tapping time, and 10 repeated opening and closings of the hands. RESULTS: A total of 224 participants were included in this study, with a mean age of 60.6 ± 10.5 years. The prevalence of CMB was 34.8% and most was lobar. Multiple linear regression analysis showed that CMB was associated with lower gait velocity, wider stride width, longer TUG test time, and poor performance on Tinetti and SPPB tests independently of other coexisting CSVD markers and risk factors. These relationships appeared to be explained by CMBs in the frontal, temporal, basal ganglia and infratentorial regions. The motor function of upper extremity also had independent correlations with CMBs especially in frontal, parietal, and temporal areas, and in the basal ganglia. CONCLUSIONS: CMBs were found to be associated with both gait, balance and upper extremity disturbances. The presence of CMB seems to be another major driving force for CSVD on lower and upper extremity impairment in healthy elderly subjects.

Age-related macular degeneration is associated with probable cerebral amyloid angiopathy: A case-control study.

BACKGROUND: Age-related macular degeneration (AMD) is a common retinal degenerative disorder among older individuals. Amyloid deposits, a hallmark of cerebral amyloid angiopathy (CAA), may be involved in the pathogenesis of AMD. Since amyloid deposits may contribute to the development of both AMD and CAA, we hypothesized that patients with AMD have a higher prevalence of CAA. OBJECTIVE: To compare the prevalence of CAA in patients with or without AMD matched for age. METHODS: We conducted a cross-sectional, 1:1 age-matched, case-control study of patients ≥40 years of age at the Mayo Clinic who had undergone both retinal optical coherence tomography and brain MRI from 2011 to 2015. Primary dependent variables were probable CAA, superficial siderosis, and lobar and deep cerebral microbleeds (CMBs). The relationship between AMD and CAA was assessed using multivariable logistic regression and was compared across AMD severity (none vs early vs late AMD). RESULTS: Our analysis included 256 age-matched pairs (AMD 126, no AMD 130). Of those with AMD, 79 (30.9%) had early AMD and 47 (19.4%) had late AMD. The mean age was 75±9 years, and there was no significant difference in vascular risk factors between groups. Patients with AMD had a higher prevalence of CAA (16.7% vs 10.0%, p=0.116) and superficial siderosis (15.1% vs 6.2%, p=0.020), but not deep CMB (5.2% vs 6.2%, p=0.426), compared to those without AMD. After adjusting for covariates, having late AMD was associated with increased odds of CAA (OR 2.83, 95% CI 1.10-7.27, p=0.031) and superficial siderosis (OR 3.40, 95%CI 1.20-9.65, p=0.022), but not deep CMB (OR 0.7, 95%CI 0.14-3.51, p=0.669). CONCLUSIONS: AMD was associated with CAA and superficial siderosis but not deep CMB, consistent with the hypothesis that amyloid deposits play a role in the development of AMD. Prospective studies are needed to determine if features of AMD may serve as biomarkers for the early diagnosis of CAA.

Segmented 3D Echo Planar Acquisition for Rapid Susceptibility-Weighted Imaging: Application to Microhemorrhage Detection in Traumatic Brain Injury.

BACKGROUND: Susceptibility-weighted imaging (SWI) provides superior image contrast of cerebral microhemorrhages (CMBs). It is based on a three-dimensional (3D) gradient echo (GRE) sequence with a relatively long imaging time. PURPOSE: To evaluate whether an accelerated 3D segmented echo planar imaging SWI is comparable to GRE SWI in detecting CMBs in traumatic brain injury (TBI). STUDY TYPE: Prospective. SUBJECTS: Four healthy volunteers and 46 consecutive subjects (38.0 ± 14.4 years, 16 females; 12 mild, 13 moderate, and 7 severe TBI). FIELD STRENGTH/SEQUENCE: A 3 T scanner/3D gradient echo and 3D segmented echo planar imaging (segEPI). ASSESSMENT: Brain images were acquired using GRE and segEPI in a single session (imaging time = 9 minutes 47 seconds and 1 minute 30 seconds, respectively). The signal-to-noise ratio (SNR) calculated from healthy volunteer thalamus and centrum semiovale were compared. CMBs were counted by three raters blinded to diagnostic information. STATISTICAL TESTS: A t-test was used to assess SNR difference. Pearson correlation and Wilcoxon signed-rank test were performed using CMB counts. The intermethod agreement was evaluated using Bland-Altman method. Intermethod and interrater reliabilities of image-based diffuse axonal injury (DAI) diagnoses were evaluated using Cohen's kappa and percent agreement. P ≤ 0.05 was considered statistically significant. RESULTS: Thalamus SNRs were 16.9 ± 2.2 and 16.5 ± 3 for GRE and segEPI (P = 0.84), respectively. Centrum semiovale SNRs were 25.8 ± 4.6 and 21.1 ± 2.7 (P = 0.13). The correlation coefficient of CMBs was 0.93, and differences were not significant (P = 0.56-0.85). For DAI diagnoses, Cohen's kappa was 0.62-0.84 and percent agreement was 85%-94%. DATA CONCLUSION: CMB counts on segEPI and GRE were highly correlated, and DAI diagnosis was made equally effectively. segEPI SWI can potentially replace GRE SWI in detecting TBI CMBs, especially when time constraints are critical. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Spatial distribution of cerebral microbleeds reveals heterogeneous pathogenesis in CADASIL.

OBJECTIVES: Radiological diagnosis of subtypes of cerebral small vessel diseases remains challenging. This study aimed to explore the spatial distribution of cerebral microbleeds (CMBs) in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) in contrast to cerebral amyloid angiopathy (CAA) in the lobar regions. METHODS: Thirty-two patients with CADASIL and 33 patients with probable CAA were prospectively and consecutively included. On 3-Tesla susceptibility-weighted magnetic resonance images, CMBs were analyzed for incidence and volume within atlas-based regions of interest, followed by voxel-wise analysis using risk mapping. The distribution of CMBs was correlated with the status of hypertension. Correlation and group differences with a p-value less than 0.05 were considered to be significant. RESULTS: As compared with the CAA group, the CADASIL group presents a larger CMB volume in hippocampus/amygdala and white matter (nonparametric analysis of covariance, p = 0.014 and 0.037, respectively), a smaller CMB volume in parietal lobe (p = 0.038), and a higher incidence in hippocampus/amygdala, white matter, and insula (logistic regression, p = 0.019, 0.024, and 0.30, respectively). As part of the exclusion criteria of probable CAA, thalamus, basal ganglia, and pons exhibit greater CMB volume/incidence in the CADASIL group. In CADASIL patients, hot spots of CMBs are identified in the putamen and posteromedial thalamus; hypertension is associated with larger CMB volumes in insula, basal ganglia, and pons. CONCLUSIONS: The spatial distribution of CMBs is differentiable between CADASIL and CAA in lobar regions. In CADASIL patients, hypertension has a region-dependent mediating effect on the CMB volume. KEY POINTS: • The topological distribution of lobar CMBs is differentiable between CADASIL and CAA. • In CADASIL patients, hypertension mediates CMB volume and the mediation is region dependent. • CMB risk mapping allows for voxel-wise exploration of CMB distribution and reveals hot spots in the putamen and posteromedial thalamus in CADASIL.

Comparison of clinical and neuroimaging features between NOTCH3 mutations and nongenetic spontaneous intracerebral haemorrhage.

BACKGROUND AND PURPOSE: The NOTCH3 mutation is a common cause of hereditary cerebral small vessel disease (CSVD) and may be a cause of spontaneous intracerebral haemorrhage (ICH). The aim was to investigate the clinical/imaging features for identifying the NOTCH3-mutation-related ICH. METHODS: The study was based on a cohort of 749 CSVD patients in Taiwan who received next-generation sequencing of CSVD genes including NOTCH3. Patients with a history of ICH (n = 206) were included for analysis. The CSVD neuroimaging markers were compared between the patients with NOTCH3 and those without known genetic mutations. RESULTS: After excluding patients with other causes of ICH (structural lesions, systemic/medication related or amyloid angiopathy) and those without neuroimaging, 45 NOTCH3 mutation patients and 109 nongenetic ICH patients were included. The NOTCH3 mutation patients were more likely to have thalamic haemorrhage, a family history of stroke and more severe CSVD neuroimaging markers. A five-point NOTCH3-ICH score was constructed and consisted of a history of stroke in siblings, thalamic haemorrhage, any deep nuclei lacunae, any hippocampal cerebral microbleed (CMB) and a thalamic CMB >5 (one point for each). A score ≥2 had a sensitivity of 88.9% and a specificity of 64.2% in identifying the NOTCH3 mutation. The NOTCH3 mutation patients had a higher risk of recurrent stroke (9.1 vs. 4.5 per 100 person-years, log-rank p = 0.03) during follow-up. CONCLUSION: The patients with NOTCH3-mutation-related ICH had a higher burden of CMBs in the hippocampus/thalamus and a higher recurrent stroke risk. The NOTCH3-ICH score may assist in identifying genetic causes of ICH.

Patterns and Predictors of Extra-Corporeal Membrane Oxygenation Related Cerebral Microbleeds.

OBJECTIVES: Recent case-reports have described an atypical cerebral microbleed (CMB) topography after extracorporeal membrane oxygenation (ECMO). The objective of this study was to examine the prevalence, radiographic patterns, and clinical correlates of possibly-ECMO-related (PER) CMB. MATERIALS AND METHODS: We performed a retrospective study of 307 consecutive patients receiving ECMO support at our tertiary-care University Hospital (2013-2018). PER CMB were defined as CMB present in corpus-callosum and/or middle cerebellar peduncle with/without involvement of other lobar/deep structures. Leukoaraiosis was quantified using the Wahlund age-related white matter changes scale. Patient characteristics were compared between cohorts with and without PER CMB. RESULTS: Forty patients (median age 60 years; 33% vv-ECMO and 67% va-ECMO) received at-least one MRI-brain within 3 months of ECMO support. CMB were present in 77.5% (n = 31) patients with 39% (n = 12), 17% (n = 5), and 44% (n = 14) having low (< 10 CMB), moderate (10-30 CMB), and high (> 30 CMB) burden respectively. Among CMB-positive patients, 71% (n = 22) had PER CMB, with 91% of such cases demonstrating involvement of splenium. Leukoaraiosis did not corelate to PER CMB presence (p = 0.267) or burden (ρ = 0.09). Patients with PER CMB had higher rates of ischemic stroke (50 vs. 33%), intracranial hemorrhage (41 vs. 17%), and all-cause mortality (27 vs. 17%); with survivors demonstrating no differences in their discharge disposition or modified Rankin Score. CONCLUSIONS: Post-ECMO cerebral microbleeds have a distinct distribution pattern that commonly involves the splenium of corpus-callosum. Their etiopathogenesis may be independent of microvascular lipohyalinosis. This requires further study in a larger sample-size.

Advance of antithrombotic treatment in patients with cerebral microbleed.

With the elder proportion increasing and the antithrombotic agents widely using as well as the newly magnetic resonance imaging sequence emerging, the detection rate of cerebral microbleed (CMB) is gradually raising in recent years. As we all know that CMB mainly reflects the severity of deeply small vessel lesions, which predicts hemorrhagic transformation. Whereby, to some patients with both CMB and remarkable antithrombotic indication, treatment becomes a dilemma. We have to face the challenge of weighing the pros and cons of both drug indication and bleeding risk when making a proper decision for patients. This study summarized recent advance on CMB diagnosis and treatment, to provide a useful reference to physicians in their clinical practice.

Cerebral microbleeds in neurological practice: concepts, diagnostics and clinical aspects.

INTRODUCTION: Due to the widespread use of magnetic resonance imaging (MRI) in neurological diagnostics, the number of patients detected as having cerebral microbleeds (CMBs) continues to increase. However, their clinical impact still remains controversial, especially the question of whether CMBs significantly increase the risk of life-threatening intracerebral haemorrhage (ICH) in patients undergoing intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT), or in patients on anticoagulant therapy or statins. STATE OF THE ART: The term 'CMB' is a radiological concept that aims to illustrate microscopic pathology of perivascular hemosiderin deposits corresponding most probably to small foci of past bleeding. MRI images in sequence T2*-GRE and susceptibility-weighted imaging (SWI) are used for a diagnosis of a CMB. This review summarises the current knowledge regarding the definition, prevalence, genetics, risk factors, radiological diagnosis and differential diagnosis of a CMB. We discuss its role as an indicator of future ischaemic or haemorrhagic events in high risk patients or those on antiplatelet or anticoagulant therapy, and its prognostic value for reperfusion strategies and for the development of dementia. FUTURE DIRECTION: The place of CMBs in current guidelines is explored herein. It must be emphasised that the recommendations relating to CMBs are expert opinions. Therefore, at the end of this review, we pose a number of questions that future clinical trials should answer.

Magnetic resonance imaging assessment of cerebral small vessel disease intensification in patients with severe aortic valve stenosis.

PURPOSE: To assess the prevalence of the neuroradiological indices of cerebral small vessel disease (CSVD) in patients with severe aortic valve stenosis (AS) in magnetic resonance imaging (MRI). MATERIAL AND METHODS: 34 patients (age 60-90 years, 17 women and 17 men) with severe AS and 50 healthy controls (age 61-85 years, 29 women and 21 men) underwent MRI brain examinations, which were analysed for the neuroradiological indices of CSVD: hyperintensities in periventricular white matter (PVWM) and deep white matter (DWM), enlarged perivascular spaces (ePVS), lacunar strokes, and cerebral microbleeds (CMBs). RESULTS: PVWM hyperintensities were found in 46% of volunteers and was significantly lower (p = 0.027), corresponding to AS patients (80%), the density of lesions was higher in the AS group than in controls (p = 0.019). DWM hyperintensities were found more often in AS patients (76%) than in controls (66%) (p = 0.303), but the densities were similar in both groups. Lacunar strokes were found in 35% of AS patients and 16% of controls (p = 0.042). The average number of lacunar strokes per person was 0.9 in the AS group and 0.3 in the controls (p = 0.035). The AS group showed higher variance in the number of strokes: SD = 1.96 vs. SD = 1.06 in controls. Both prevalence and density of the ePVS and CMBs did not differ significantly between the groups. CONCLUSIONS: Neuroradiological indices of the vascular disease do not provide an unequivocal clue to the pathogenesis of CSVD in patients with severe AS. Most observations imply that CSVD is primarily a consequence of cerebral hypoperfusion caused by AS.

Microbleeds and Outcome in Patients With Acute Ischemic Stroke and Atrial Fibrillation Taking Anticoagulants.

BACKGROUND AND PURPOSE: We investigated the impact of the presence, burden, and location of cerebral microbleeds (CMBs) on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in patients with acute ischemic stroke and atrial fibrillation treated with oral anticoagulants (OACs). We also examined whether the clinical effect of CMBs differs according to the type of OACs. METHODS: A total of 1742 patients with acute ischemic stroke and atrial fibrillation treated with OACs were enrolled in this cohort study. The primary composite outcome was the occurrence of MACCE (a composite of stroke, acute myocardial infarction, or vascular death) over a 2-year period according to CMB status. RESULTS: CMB presence was significantly associated with the risk of future MACCE (hazard ratio, 1.89 [95% CI, 1.23-2.88]; P=0.003) after adjustment for confounders in patients with acute ischemic stroke and atrial fibrillation taking OACs. Patients with exactly 1 CMB had a similar rate of MACCE compared with those without CMBs (P=0.461). However, patients with multiple CMBs (≥2), particularly high burden CMBs (≥5), had a significantly higher proportion of MACCE. Both CMB-positive groups with lobar and deep CMB had more frequent MACCE than the CMB-negative group, and the rate of MACCE was not different according to CMB location. In patients treated with warfarin, CMB was significantly associated with a risk of MACCE (P=0.002), but not in patients treated with direct OACs (P=0.517). CONCLUSIONS: The study results indicate that the risk of future MACCE increased with increasing CMB burden in patients with AIS and atrial fibrillation taking OACs, while the anatomic location of CMBs did not influence the risk of future MACCE. This risk seemed to be more apparent in patients taking warfarin.

Traumatic microbleeds persist for up to five years following traumatic brain injury despite resolution of other acute findings on MRI.

OBJECTIVE: The primary objective of this study was to track the incidence and progression of traumatic microbleeds (TMBs) for up to five years following traumatic brain injury (TBI). METHODS: Thirty patients with mild, moderate, or severe TBI received initial MRI within 48 h of injury and continued in a longitudinal study for up to five years. The incidence and progression of MRI findings was assessed across the five year period. In addition to TMBs, we noted the presence of other imaging findings including diffusion weighted imaging (DWI) lesions, extra-axial and intraventricular hemorrhage, hematoma, traumatic meningeal enhancement (TME), fluid-attenuated inversion recovery (FLAIR) hyperintensities, and encephalomalacia. RESULTS: TMBs were observed in 60% of patients at initial presentation. At one-year follow-up, TMBs were more persistent than other neuroimaging findings, with 83% remaining visible on MRI. In patients receiving serial MRI 2-5 years post-injury, acute TMBs were visible on all follow-up scans. In contrast, most other imaging markers of TBI had either resolved or evolved into ambiguous abnormalities on imaging by one year post-injury. CONCLUSIONS: These findings suggest that TMBs may serve as a uniquely persistent indicator of TBI and reinforce the importance of acute post-injury imaging for accurate characterization of persistent imaging findings.

Asymptomatic Striatocapsular slit-like Hemorrhage as a Severity Marker in Patients with Hypertensive Angiopathy.

BACKGROUND: Concomitant asymptomatic striatocapsular slit-like hemorrhage (SSH) is occasionally found in patients of spontaneous intracerebral hemorrhage (ICH), but was seldomly described in the literature. In this study, we described the clinico-radiological features of asymptomatic SSH in ICH patients with hypertensive microangiopathy. METHODS AND RESULTS: 246 patients with strictly deep or mixed deep and lobar ICH/microbleeds were included. SSH was defined as hypointense lesions involving the lateral aspect of lentiform nucleus or external capsule in slit shape (>1.5 cm) on susceptibility-weighted imaging without history of associated symptoms. Demographics and neuroimaging markers were compared between patients with SSH and those without. Patients with SSH (n=24, 10%) and without SSH had comparable age (62.0 ± 12.6 vs. 62.3 ± 13.5, p = 0.912) and vascular risk factor profiles including the diagnosis of chronic hypertension, diabetes, and dyslipidemia (all p>0.05). SSH was associated with more common lobar microbleeds (79.2% vs 48.2%, p = 0.005), lacunes (75% vs. 41.4%, p = 0.002) and higher white matter hyperintensity (WMH) volumes (24.1 [10.4-46.3] vs. 13.9 [7.0-24.8] mL, p = 0.012) on MRI, as well as more frequent left ventricular hypertrophy (LVH) (50.0% vs. 20.5%, p = 0.004) and albuminuria (41.7% vs. 19.4%, p = 0.018). In multivariable analyses, SSH remains independently associated with LVH (p = 0.017) and albuminuria (p = 0.032) after adjustment for age, sex, microbleed, lacune and WMH volume. CONCLUSIONS: Asymptomatic SSH is associated with more severe cerebral small vessel disease-related change on brain MRI, and hypertensive cardiac and renal injury, suggesting a more advanced stage of chronic hypertension.

[Analysis of Diagnosis and Treatment of 6 Cases of Cerebral Amyloid Angiopathy-related Inflammation].

Cerebral amyloid angiopathy associated with inflammation (CAA-ri) is characterized by an inflammatory response to the vascular deposits of ß-amyloid within the brain that is a very rare subtype of cerebral amyloid angiopathy.The most common clinical manifestation of CAA-ri was headache, epilepsy, and cognitive dysfunction. Magnetic resonance imaging (MRI) showed focal or multiple white matter lesions, lobar intracerebral hemorrhage, extensive cortical or subcortical microbleeds. We reported 6 cases of probable CAA-ri diagnosed and treated in our hospital from January 2017 to September 2019 according to the revised diagnostic criteria in 2016.We found that 5 patients also had microbleeds and cortical superficial siderosison T2 and fluid-attenuated inversion recovery (FLAIR), suggesting that if the patients had a long course of disease, older age and heavy microbleeds load, the lesions could be found in the routine MRI, which is a clue for the diagnosis of CAA-ri. Clinicians should attach great importance to this phenomenon, and can further verify by susceptibility weighted imaging (SWI).