Number Of Cerebral Microbleeds Research Articles

Automated quantification of cerebral microbleeds in susceptibility-weighted MRI: association with vascular risk factors, white matter hyperintensity burden, and cognitive function.

To train and validate a deep learning (DL)-based segmentation model for cerebral microbleeds (CMB) on susceptibility-weighted MRI; and to find associations between CMB, cognitive impairment, and vascular risk factors. Participants in this single-institution retrospective study underwent brain MRI to evaluate cognitive impairment between January-September 2023. For training the DL model, the nnU-Net framework was used without modifications. The DL model's performance was evaluated on independent internal and external validation datasets. Linear regression analysis was used to find associations between log-transformed CMB numbers, cognitive function (mini-mental status examination [MMSE]), white matter hyperintensity (WMH) burden, and clinical vascular risk factors (age, sex, hypertension, diabetes, lipid profiles, and body mass index). Training of the DL model (n = 287) resulted in a robust segmentation performance with an average dice score of 0.73 (95% CI, 0.67-0.79) in an internal validation set, (n = 67) and modest performance in an external validation set (dice score = 0.46, 95% CI, 0.33-0.59, n = 68). In a temporally independent clinical dataset (n = 448), older age, hypertension, and WMH burden were significantly associated with CMB numbers in all distributions (total, lobar, deep, and cerebellar; all P <.01). MMSE was significantly associated with hyperlipidemia (β = 1.88, 95% CI, 0.96-2.81, P <.001), WMH burden (β = -0.17 per 1% WMH burden, 95% CI, -0.27-0.08, P <.001), and total CMB number (β = -0.01 per 1 CMB, 95% CI, -0.02-0.001, P = .04) after adjusting for age and sex. The DL model showed a robust segmentation performance for CMB. In all distributions, CMB had significant positive associations with WMH burden. Increased WMH burden and CMB numbers were associated with decreased cognitive function. CMB = cerebral microbleed; DL = deep learning, DSC = dice similarity coefficient; MMSE = mini-mental status examination; SVD = small vessel disease; SWI = susceptibility-weighted image; WMH = white matter hyperintensity.

Relationship between radiation dose and cerebral microbleed formation in dogs with intracranial tumors.

Cerebral microbleeds (CMBs) are a possible sequela in human brain tumor patients treated with radiation therapy (RT). No such association is reported in dogs. To investigate whether CMBs occur in dogs after radiotherapy, and if there is an association between number and dose, and an increase over time. Thirty-four client-owned dogs irradiated for primary intracranial neoplasia. ≥2 magnetic resonance imaging (MRI) scans including susceptibility-weighted imaging (SWI) were required. Retrospective, observational, single-center study. Cerebral microbleeds identified on 3 T SWI were counted within the entire brain, and within low- (<20 Gy), intermediate- (20-30 Gy), and high- (>30 Gy) dose regions. A generalized linear mixed-effects model was used to analyze the relationship between the CMBs count and the predictor variables (irradiation dose, time after treatment). Median follow-up time was 12.6 months (range, 1.8-37.6 months). Eighty-three MR scans were performed. In 4/15 dogs (27%, 95% CI, 10%-52%) CMBs were present at baseline. ≥1 CMBs after RT were identified in 21/34 dogs (62%, 95% CI, 45%-77%). With each month, the number of CMBs increased by 14% (95% CI, 11%-16%; P < .001). The odds of developing CMBs in the high-dose region are 4.7 times (95% CI, 3.9-5.6; P < .001) greater compared with the low-dose region. RT is 1 possible cause of CMBs formation in dogs. Cerebral microbleeds are most likely to occur in the peritumoral high-dose volume, to be chronic, and to increase in number over time. Their clinical relevance remains unknown.

Cerebral microbleeds in acute ischemic stroke after intravenous thrombolysis and their impact on short term outcome of stroke

Objectives Strong evidence suggests the occurrence of cerebral microbleeds (CMBs) in 5–13% of stroke patients within the first week after stroke onset. The aim of this work was to study risk factors associated with occurrence of CMBs in patients with stroke who received intravenous thrombolysis, and to clarify their impact on the clinical outcome. Methods This prospective observational study was conducted on 61 acute ischemic stroke patients eligible for treatment with recombinant tissue plasminogen activator (rt-PA). Assessment of stroke-related neurologic deficit was done using National Institute of Health Stroke Scale (NIHSS). Assessment of stroke related disability after 3 months from stroke onset was done using Modified Rankin Scale (mRS). CMBs were detected by T2*-weighed gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences. Results There was a statistically significant impact of age, mean arterial pressure (MAP) at stroke onset, history of hypertension (HTN), and white matter changes assessed by Fazekas scale on the occurrence of CMBs in the included stroke patients (P-value= 0.002, <0.001, <0.001, 0.008 respectively). There was no statistically significant difference between patients with favorable and those with unfavorable outcome regarding the total number of CMBs (P-value =0.542). There was also no statistically significant difference between patients who developed complications from rt-PA and those who didn’t develop regarding the total number of CMBs (P-value =0.186). Conclusion Cerebral microbleeds are more likely to occur in older stroke patients and in those who had high MAP at stroke onset, history of HTN, and white matter changes.

Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction/Disruption with Increased Risk of Hemorrhagic and Ischemic Stroke.

Globally, cerebral microbleeds (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5 mm, smooth, round, or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences MRI images. CMBs are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and is only expected to continue to grow, we can expect the healthcare burdens associated with CMBs to also grow. Increased numbers (≥10) of CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Herein author highlights that it is essential to learn as much as we can about CMB development, evolution, and their relation to impaired cognition, dementia, and the exacerbation of neurodegeneration.

Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77–9.50]mm2/s × 10−4) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm2/s × 10−4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16–0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08–0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22–0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13–0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = −0.42 [−0.69–0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.

Cerebral microbleeds is a predictor of recurrent small vessel cerebrovascular disease: Evaluation based on the recurrent stroke pattern

ObjectivesAn increased number of cerebral microbleeds (CMBs) is considered a predictive factor for recurrent small vessel cerebrovascular diseases, including lacunar infarction and non-lobar intracerebral hemorrhage (ICH). However, it is unclear which recurrent stroke pattern is mainly reflected in the number of CMBs. Materials and MethodsThis study enrolled 217 patients with their first stroke (148 deep lacunar infarctions and 69 non-lobar ICHs), between January 2009 and March 2015. The numbers of baseline and newly appearing CMBs in patients with recurrent stroke were compared with those in patients with non-recurrent stroke, and the dynamics of the number of CMBs was evaluated according to recurrent stroke patterns. ResultsFifty-nine patients with recurrent stroke were included in this study. A larger number of baseline and newly appearing CMBs was significantly associated with recurrent stroke (p = 0.04, p < 0.001, respectively). Recurrent stroke patterns were divided into four types: deep lacunar infarction/deep lacunar infarction (37 patients), deep lacunar infarction/non-lobar ICH (eight patients), non-lobar ICH/deep lacunar infarction (eight patients), and non-lobar ICH/non-lobar ICH (six patients). The number of newly appearing CMBs was significantly higher in patients with deep lacunar infarction/non-lobar ICH than in those with other recurrent stroke patterns (p = 0.04). ConclusionsThe number of CMBs is associated with recurrent stroke, including deep lacunar infarction and non-lobar ICH, and differs depending on the recurrent stroke patterns. The increase in the number of CMBs was strongly correlated with the deep lacunar infarction/non-lobar ICH recurrence pattern.

Clinical characteristics of cerebral amyloid angiopathy and risk factors of cerebral amyloid angiopathy related intracerebral hemorrhage.

There is limited understanding of the differences between cerebral amyloid angiopathy (CAA) with and without intracerebral hemorrhage (ICH). This article aimed to describe the characteristics of CAA and identify the risk factors of CAA-ICH in a multicenter cohort. Patients consecutively enrolled in the national multicenter prospective Cerebral Small Vessel Disease Cohort Study who met the Boston diagnostic criteria for CAA or CAA-related inflammation were included in this study. The demographic characteristics and clinical data were collected. The clinical and radiographic differences between CAA with and without ICH were compared to identify the risk factors for CAA-ICH. A total of 219 CAA patients were included, with an average age of 67.12 ± 9.93. Of all patients, 26.0% were CAA with ICH. Univariate analysis showed that CAA-ICH is associated with carrying more APOE ε2 allele, less lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), lower Fazekas scale, a tendency of gait disorder, and acute onset (P < 0.05). The generalized linear mixed model yielded statistically significant associations between CAA with ICH and carrying the APOE ε2 allele, cSS, the lower number of lobar CMBs, and the lower Fazekas scale (P < 0.05). It is meaningful to classify CAA with and without ICH, as there may be different mechanisms between the two. CAA with ICH has a susceptibility to carrying APOE ε2, cSS, and a relatively small number of CMBs. Fewer CMBs do not mean lower susceptibility to ICH in CAA. Larger prospective cohort studies are necessary to further clarify these conclusions.

Literature Review on the Association between Cerebral Large Artery Disease and Cerebral Microbleeds

CMBs are small areas of hemorrhage in the brain, often seen on neuroimaging studies, that have been associated with various cerebrovascular pathologies. Large-artery atherosclerosis and resulting vascular stenosis are major contributors to ischemic stroke. Given the structural continuity between intracranial large and small vessels, their susceptibility to hemodynamic influences, and their shared risk factors, they may coexist in the same individual. This article reviews recent advances in understanding the interplay between large artery atherosclerosis (LAA) and cerebral microbleeds (CMB). Methods: A comprehensive search of electronic databases including PubMed, MEDLINE, and Google Scholar was conducted using relevant keywords such as "cerebral large artery disease," "cerebral microbleeds," "arterial stenosis," and "atherosclerosis." Articles published in English between [2010] and [2024] were considered for inclusion. Studies investigating the relationship between LAA and CMBs through neuroimaging, pathological examination, or clinical correlations were selected for review. Results: The review identified a range of studies exploring the association between LAA and CMBs. Several cross-sectional imaging studies have demonstrated a significant correlation between LAA severity and the presence, number, and distribution of CMBs. Histopathological investigations have revealed microvascular alterations in regions affected by LAA, potentially contributing to CMB formation. The evidence indicates a correlation between cerebrovascular microbleeds (CMBs) and large artery diseases, impacting the prognosis of individuals with cerebral infarction resulting from large artery atherosclerosis (LAA). Keywords: Cerebral infarction; Large-artery atherosclerosis; Cerebral microbleeds.

COVID-19-associated cerebral microbleeds in the general population.

Cerebral microbleeds are frequent incidental findings on brain MRI and have previously been shown to occur in Coronavirus Disease 2019 (COVID-19) cohorts of critically ill patients. We aimed to determine the risk of having microbleeds on medically indicated brain MRI and compare non-hospitalized COVID-19-infected patients with non-infected controls. In this retrospective case-control study, we included patients over 18 years of age, having an MRI with a susceptibility-weighted sequence, between 1 January 2019 and 1 July 2021. Cases were identified based on a positive reverse transcriptase polymerase chain reaction test for SARS-CoV-2 and matched with three non-exposed controls, based on age, sex, body mass index and comorbidities. The number of cerebral microbleeds on each scan was determined using artificial intelligence. We included 73 cases and 219 matched non-exposed controls. COVID-19 was associated with significantly greater odds of having cerebral microbleeds on MRI [odds ratio 2.66 (1.23-5.76, 95% confidence interval)], increasingly so when patients with dementia and hospitalized patients were excluded. Our findings indicate that cerebral microbleeds may be associated with COVID-19 infections. This finding may add to the pathophysiological considerations of cerebral microbleeds and help explain cases of incidental cerebral microbleeds in patients with previous COVID-19.

Outcomes of patients with cerebral microbleeds undergoing percutaneous coronary intervention and dual antiplatelet therapy.

Cerebral microbleeds (CMBs) on brain magnetic resonance imaging (MRI) are predictive of intracerebral hemorrhage (ICH). However, the risk of ICH in patients with CMBs who undergo percutaneous coronary intervention (PCI) while receiving dual antiplatelet therapy (DAPT) is unclear. We conducted a study on 329 consecutive patients with coronary artery disease who underwent PCI and were evaluated using a 3T MRI scanner. Based on T2*-weighted imaging, patients were classified into three groups: no CMBs, < 5 CMBs, or ≥ 5 CMBs. We determined the occurrence of ICH during follow-up. At least 1 CMB was found in 109 (33%) patients. The mean number of CMBs per patient was 2.9 ± 3.6. Among the 109 patients with CMBs, 16 (15%) had ≥ 5 CMBs. Coronary stent implantation was performed in 321 patients (98%). DAPT was prescribed for 325 patients (99%). During a mean follow-up period of 2.3 years (interquartile range, 1.9-2.5 years), ICH occurred in one patient (1.1%) with four CMBs. There were no significant differences in the incidence of ICH (0% vs. 1.1% vs. 0%; p = 0.28). However, the rate of DAPT at 6 months of follow-up was significantly lower in patients with ≥ 5 CMBs than in patients with no CMBs or < 5 CMBs (89% vs. 91% vs. 66%, p = 0.026). Furthermore, there were no significant differences in systemic blood pressure during follow-up (123 ± 16 vs. 125 ± 16 vs. 118 ± 11 mmHg; p = 0.40). Although a substantial number of patients who underwent PCI had cerebral microbleeds, at approximately two years of follow-up, intracerebral hemorrhage was very rare in our study population.

Automatic detection of cerebral microbleeds using susceptibility weighted imaging and artificial intelligence.

Efficiently and accurately detecting cerebral microbleeds (CMBs) is crucial for diagnosing dementia, stroke, and traumatic brain injury. Manual CMB detection, however, is time-consuming and error-prone. This study evaluates a novel artificial intelligence (AI) software designed for the automated detection of CMBs using susceptibility weighted imaging (SWI). The SWI data from 265 patients, 206 of whom had a history of stroke and others of whom presented a variety of other medical histories, including hypertension, diabetes, hyperlipidemia, cerebral hemorrhage, intracerebral vascular malformations, tumors, and inflammation, collected between January 2015 and December 2018, were analyzed. Two independent radiologists initially reviewed the images to identify and count the number of CMBs. Subsequently, the images were processed using an automatic CMB detection software. The generated reports were then reviewed by the radiologists. A final consensus between the two radiologists, obtained after a second review of the images, was used to compare results obtained from the initial manual detection and those of the automatic CMB detection software. The differences of detection sensitivity and precision for patients with or without CMBs and for individual CMBs between the radiologist and the automatic CMB detection software were compared using Pearson chi-squared tests. A total of 1,738 CMBs were detected among 148 patients (71.4±10.7 years, 100 males) from the analyzed SWI data. While the radiologists identified 139 cases with CMBs, the automatic CMB detection software detected 145 cases. Nevertheless, there was no statistical difference in the sensitivity and specificity of the automatic CMB detection software compared to manual detection in determining patients with CMBs (P=0.656 and P=0.212, chi-square test). However, the radiologist identified 93 patients without CMBs, while the automatic CMB detection software detected 121 patients without CMBs, exhibiting a statistically significant difference (P=0.016, chi-square test). In terms of individual CMBs, the radiologists found 1,284, whereas the automatic CMB detection software detected 1,677 CMBs. The detection sensitivity for human versus the automatic CMB detection software were 75.5% and 96.5% respectively (P<0.001, chi-square test), while the precision rates were 92.2% and 86.0% (P<0.001, chi-square test), respectively. Notably, the radiologists were more likely to overlook CMBs when the number of CMBs was high (above 30). The automatic CMB detection software proved to be an effective tool for the detection and quantification of CMBs. It demonstrated higher sensitivity than the radiologists, especially in detecting minuscule CMBs and in cases with high CMB prevalence.

Associations of Growth-Associated Protein 43 with Cerebral Microbleeds: A Longitudinal Study.

Cerebral microbleeds (CMB) play an important role in neurodegenerative pathology. The present study aims to test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) level is linked to CMBs in elderly people. A total of 750 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had measurements of GAP-43 and CMBs were included in the study. According to the presence and extent of CMBs, participants were stratified into different groups. Regression analyses were used to assess cross-sectional and longitudinal associations between GAP-43 and CMBs. Participants with CMB were slightly older and had higher concentrations of CSF GAP43. In multivariable adjusted analyses for age, gender, APOEɛ4 status, and cognitive diagnoses, higher CSF GAP-43 concentrations were modestly associated with CMB presence (OR = 1.169, 95% CI = 1.001-1.365) and number (β= 0.020, SE = 0.009, p = 0.027). Similarly, higher CSF GAP43 concentrations were accrual of CMB lesions, associated with higher CMB progression (OR = 1.231, 95% CI = 1.044-1.448) and number (β= 0.017, SE = 0.005, p = 0.001) in the follow up scan. In stratified analyses, slightly stronger associations were noted in male participants, those 65 years and older, carriers of APOEɛ4 alleles, and with more advanced cognitive disorders. CSF GAP-43 was cross-sectionally associated with the presence and extent of CMBs. GAP-43 might be used as a biomarker to track the dynamic changes of CMBs in elderly persons.

Research Advancements on the Correlation Between Spontaneous Intracerebral Hemorrhage of Different Etiologies and Imaging Markers of Cerebral Small Vessel Disease.

The purpose of this review is to identify the correlation between ICH and CSVD imaging markers under SMASH-U classification by searching and analyzing a large number of literatures in recent years, laying a theoretical foundation for future clinical research. At the same time, by collecting clinical data to evaluate patient prognosis, analyzing whether there are differences or supplements between clinical trial conclusions and previous theories, and ultimately guiding clinical diagnosis and treatment through the analysis of imaging biomarkers. In this review, by searching CNKI, Web of Science, PubMed, FMRS and other databases, the use of "spontaneous intracerebral hemorrhage", "hypertensive hemorrhagic cerebral small vessel disease", "cerebral small vessel disease imaging", "Based cerebral small vessel diseases", "SMASH the -u classification" and their Chinese equivalents for the main search term. We focused on reading and analyzing hundreds of relevant literatures in the last decade from August 2011 to April 2020, and also included some earlier literatures with conceptual data sources. After screening and ranking the degree of relevance to this study, sixty of them were cited for analysis and elaboration. In patients with ICH, the number of cerebral microbleeds in lobes, basal ganglia, and the deep brain is positively correlated with ICH volume and independently correlated with neurological functional outcomes; white matter hyperintensity severity is positively correlated with ICH recurrence risk; multiple lacunar infarction independently predict the risk of ICH; severe brain atrophy is an independent risk factor for a poor prognosis in the long term in patients diagnosed with ICH; and the number of enlarged perivascular spaces is correlated with ICH recurrence. However, small subcortical infarct and ICH are the subject of few studies. Higher CSVD scores are independently associated with functional outcomes at 90 days in patients diagnosed with ICH.

Abstract WMP67: Pump Brain - A Leading Cause of Cortical Cerebral Microbleeds

Introduction: A major cause of cerebral microbleeds (CMBs) is underrecognized and has been attributed to cerebral amyloid angiopathy (CAA) throughout modern medicine. CMBs are acquired by patients undergoing cardiopulmonary bypass (CPB). CPB is utilized for heart and lung transplants, aorta repairs, valve surgeries, mass resections, and coronary artery bypass grafting (CABG) which alone accounts for 400k patients per year. CABGs can be done off CPB in certain patients. Due to their distribution, these CMBs are attributed to CAA, leading to confounding research and suboptimal patient care, especially in those requiring anticoagulation. Methods: This was a single-center, IRB approved, retrospective cohort study of patients who underwent CPB and had postop MRI between 11/1/11 and 3/1/23. Preop and additional postop MRIs were analyzed if available. Outcomes included number and distribution of CMBs, presence of superficial siderosis, FAZEKAS, and CPB duration. We also analyzed MRIs of patients who had off CPB CABG during the same period. Results: Out of 60 patients who underwent CPB, 60 had predominantly cortical CMBs on postop MRI, with a mean of 50 CMBs, and mean age of 61. The 6 patients who had CABG off CPB had 0 CMBs. Higher CMBs were associated with longer CPB duration and with procedures that are associated with more blood loss (p&lt; 0.05). Despite having CMBs, no CPB patients had superficial siderosis, and they had relatively low FAZEKAS scores. Nineteen of the CPB patients had future MRIs and had no evidence of CMB progression. Conclusion: Cortical CMBs are associated with procedures that use CPB and are not seen in off CPB CABG. The CMBs may be related to utilization of cardiotomy suction that exclusively uses roller pumps. CBP related CMBs are a unique clinical entity that is not associated with the progressive cognitive changes and bleeding risk of CAA. While no significant short-term changes are noted, their mechanism and natural history requires further investigation.

Artificial intelligence‐driven algorithm to detect and count cerebral microbleeds on Susceptibility Weighted Imaging

AbstractBackgroundAmyloid‐related imaging abnormalities (ARIA)‐H, characterized by cerebral microbleeds (CMB) and superficial siderosis, is an important Magnetic Resonance Imaging(MRI) finding observed in the patients with Alzheimer’s disease, especially receiving the anti‐amyloid immunotherapy. Because the severity of CMB can potentially lead to discontinuation of the therapy, the detection and counting of the CMB would be critical tasks in MRI analysis. We present an algorithm which can detect CMBs and count the number of them, automatically and accurately.MethodWe employed datasets of both SWI and phase images, developed in collaboration with Eunpyeong St. Mary’s Hospital, Kyung Hee, and HanYang University Medical Center. The data set comprises 463 participants with CMBs (N = 247) and without CMBs (N = 116). Experts denoted gold standard of each CMBs as bounding boxes. A localizer is trained by selecting 2D axial slices, including expert‐confirmed annotations. A modified recurrent layer was applied for weight‐sharing between two images. An optimized region proposal network was then applied. To reduce FP regions across entire slices, we developed a classifier with attention‐based 3D convolution blocks. From the CMB localizer, candidate 3D CMB patches were used in the classifier.ResultCMB prediction was performed on the test set including 140 participants (CMB:24; Non‐CMB:116), with 263 expert‐confirmed gold standard (Figure 1). The lesion‐wise sensitivity was 0.913 [95% Confidence interval (CI), 0.863‐0.963] and the average FP rate was 0.672 per patient [95% CI, 0.290‐1.154]. Patient‐wise sensitivity and specificity were 0.862 [95% CI, 0.792‐0.932] and 0.907 [95% CI, 0.880‐0.934], respectively. When we divided the patients into four groups according to the number of gold standard, the model predicted the groups correctly by the sensitivity of 0.879 [95% CI, 0.851‐0.907] (Table 1).ConclusionOur model outperformed the results of recent studies by reducing FP rate with comparable sensitivity. Moreover, our model may suggest additional clinical benefit, because it can automatically count the number of CMB and classify the participants into 4 groups, used in the clinical investigation of anti‐amyloid therapy, according to the number of CMB. We expect this model may improve the workflow of the time‐consuming reading task and act as a failsafe for the detection of CMBs.

Cerebral amyloid angiopathy frequency at baseline and after 4 years of follow‐up in the INSIGHT‐preAD study

AbstractBackgroundCerebral amyloid angiopathy (CAA) diagnostic is of special interest due to its association with cognitive impairment, Alzheimer disease (AD) and Amyloid‐Related Imaging Abnormalities (ARIA) in trials with anti‐amyloid immunotherapies. We aimed to assess the frequency of CAA diagnosis and associated lesions in subjects with cognitive complaint and normal cognition enrolled in the INSIGHT‐preAD study.MethodCognitively normal elderly with memory complaint included in the INSIGHT‐preAD study were assessed with multimodal explorations for 5 years follow‐up. 3T MRI‐scans were performed at baseline and during follow‐up at 2 and 4 years. Lobar cerebral microbleeds (CMB), cortical superficial siderosis (CSS), enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were rated according to validated scales and guidelines. Boston criteria V2.0 were applied to diagnose possible and probable CAA.ResultAmong the 318 subjects (median [Q1, Q3] age: 76.4 [74.1, 78.5] years, 201 (63.2%) women) enrolled at baseline, 41 (12.9%) had at least one lobar CMB, 4 (1.3%) CSS, 68 (21.7%) severe EPVS in the centrum semi‐ovale and 245 (77%) WMH with a spot pattern ≥10. The median FAZEKAS score was 2.0 [1.0, 2.0]. At baseline, 251 (78.9%) subjects had CAA: 218 (68.5%) possible CAA and 33 (10.4%) probable CAA with a median number of CMB of 1.0 [1.0, 1.0]. Compared to non‐CAA subjects (n = 67), those with probable CAA at baseline were not different on demographics and vascular risk factor, had more executive dysfunction, and tended to be associated with Apoe4 status and lower hippocampal volume. After 2‐ and 4‐ years of follow‐up, 81.2% and 81.3% of the subjects still in the study had CAA, with 13.3% and 14.1% of probable CAA respectively, and the number of subjects with CMB increased to 15.9% and 18.3%.ConclusionIn the INSIGHT‐preAD study, the high frequence of CAA, with minimal change after 4 years follow‐up, was essentially due to the non‐hemorrhagic lesions. The hemorrhagic lesions (CMB and CSS) were uncommon, probably underestimated by the MRI T2* sequence. These results have implications in clinical setting and could be useful in pre‐symptomatic AD anti‐amyloid immunotherapy trial.

Correlation between lipid-lowering therapy and cerebral microbleeds.

To investigate if there is a correlation between lipid-lowering treatment with statins and the occurrence, number, and location of cerebral microbleeds (CMBs) among patients with ischemic cerebrovascular disease (ICVD), and also to compare treatment with atorvastatin and rosuvastatin in terms of the occurrence of CMBs and their differences. In this retrospective study, we included patients who were diagnosed with ICVD and underwent susceptibility weighted imaging (SWI) in a grade A tertiary hospital from October 1, 2014 to October 1, 2022. We collected information on previous statin use, past medical history, clinical test indicators, and imaging data. We found that out of 522 patients, 310 patients (59.4%) had no CMB and 212 patients (40.6%) had CMBs. There was no statistically significant correlation between prior statin use, the occurrence, and number of CMBs in patients diagnosed with ICVD (P < 0.05). As for the location of CMB, there was a statistically significant correlation between prior statin use and lobar CMBs (P < 0.048). However, there was no statistically significant correlation between the use of atorvastatin and rosuvastatin and the occurrence of CMBs (P > 0.05). There was no independent correlation between previous statin use, and the occurrence, and number of CMBs in patients with ICVD. As for CMBs in different locations, there was a correlation between previous use of statin and lobar CMBs. There was no significant difference between atorvastatin and rosuvastatin in the occurrence of CMBs in patients with ICVD.

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: β = 0.251, P = 0.014; volume: β = 0.237, P = 0.042; total iron burden: β = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: β = 0.325, P = 0.001; Evans's index: β = 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.

Microbleed clustering in thalamus sign in CADASIL patients with NOTCH3 R75P mutation.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan. We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL. Clinical and imaging analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. To assess the presence of cerebral microbleeds (CMBs), we utilized several established rating scales including the Fazekas scale, Scheltens rating scale, and Microbleed Anatomical Rating Scale, based on brain MRI images. Among the 32 CADASIL patients, 24 cases were found carrying the R75P mutation in NOTCH3, whereas the remaining eight cases had other NOTCH3 mutations (R75Q, R110C, C134F, C144F, R169C, and R607C). The haplotype analysis of the R75P mutation uncovered the presence of a founder effect. A brain MRI analysis revealed that cases with the R75P mutation had a significantly higher total number of CMBs, particularly in the thalamus when compared to patients with other NOTCH3 mutations. Among 15 out of 24 cases with the R75P mutation, we observed a notable clustering of CMBs in the thalamus, termed microbleed clustering in thalamus sign (MCT sign). We propose that the MCT sign observed in NOTCH3 R75P-related CADASIL patients may serve as a potentially characteristic imaging feature. This finding offers further insights into the interactions between genotypes and phenotypes between NOTCH3 and CADASIL.

Impact of previous statin use on first intracerebral hemorrhage in cerebral amyloid angiopathy

ObjectivesStatins have been associated with an increased risk of spontaneous intracerebral hemorrhage (ICH), but without dedicated study in cerebral amyloid angiopathy (CAA). We aimed to evaluate the association between previous statin treatment and radiological hemorrhagic lesions in a CAA population during a first lobar ICH event. Materials and methodsWe retrospectively included all patients meeting the modified Boston criteria for probable CAA and admitted for a first lobar ICH between 2010 and 2021 at Rouen University Hospital. Patients were classified as having previous statin treatment or not. We compared the ICH volume, the number of associated cerebral microbleeds (CMBs), and cortical superficial siderosis (CSS) according to previous statin treatment or not. We also compared functional outcomes and ICH recurrence during the follow-up period between the two groups. ResultsWe included 99 patients, 27 of whom had statin treatment prior to their ICH. The ICH volume and the number of CMBs did not differ between groups. Disseminated CSS was initially more frequent in the statin group (88% versus 57%; P=0.019), but this was no longer significant after adjustment for antiplatelet treatment (P=0.13). The long-term outcome was similar between the two groups with no increased risk of ICH recurrence in the statin-treated group (29.63% versus 23.61%, P=0.54). ConclusionsPrevious statin treatment was not associated with more severe hemorrhagic lesions in CAA in terms of ICH volume or number of microbleeds, but a trend for increased disseminated CSS was highlighted, which will require further larger studies.