Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid ß-protein (Aß) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aß promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-ß1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-ß1 pathway and increased TGF-ß1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-ß1 in the disease process.

Relationship between visual function and macular microstructure in highly myopic patients undergoing surgery for rhegmatogenous retinal detachment.

OBJECTIVE: To analyze the relationship between visual function and macular microstructure in highly myopic patients undergoing surgery for rhegmatogenous retinal detachment (RRD). METHODS: Fifty-eight highly myopic patients treated in the Baoding No. 1 Central Hospital between December 2021 and September 2023 were selected as the research participants for retrospective analysis. All patients were complicated with RRD and underwent retinal reattachment surgery at Baoding No. 1 Central Hospital after diagnosis. Best-corrected visual acuity (BCVA) examinations were performed before and 3 months after surgery, and visual field mean sensitivity (MS) and fixation stability (FS) were measured by microperimetry. Additionally, changes in postoperative macular microstructure and micro blood flow were determined by optical coherence tomography (OCT), and their correlations with visual function were analyzed. RESULTS: Patients showed reduced BCVA, MS, and FS after surgery (all P<0.05), with 70.69% of them presenting with macular microstructural changes, mainly ellipsoid zone disruption and external limiting membrane disruption. Patients with macular microstructural changes exhibited significantly decreased BCVA, MS, and FS than those without (all P<0.05). In terms of micro blood flow, the BCVA, FS, and MS of patients with macular microstructural changes were negatively correlated with the foveal avascular zone (FAZ) area but were positively related to FAZ morphological index, PSCP, and VSCP (all P<0.05). CONCLUSIONS: Changes in patients' visual function after surgery for RRD can be effectively evaluated by observing the macular ellipsoid, the integrity of the external limiting membrane, and the alterations in micro-blood flow, enabling the formulation of early and targeted interventions.

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.

The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.

Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of individuals over 80, and are linked to increased risks of vascular cognitive impairment and dementia (VCID). Hypertension is a primary risk factor for CMHs. Vascular smooth muscle cells (VSMCs) adapt to hypertension by undergoing hypertrophy and producing extracellular matrix (ECM) components, which reinforce vessel walls. Myogenic autoregulation, which involves pressure-induced constriction, helps prevent excessive pressure from damaging the vulnerable microvasculature. However, aging impairs these adaptive mechanisms, weakening vessel walls and increasing susceptibility to damage. Insulin-like Growth Factor 1 (IGF-1) is crucial for vascular health, promoting VSMC hypertrophy, ECM production, and maintaining normal myogenic protection. IGF-1 also prevents microvascular senescence, reduces reactive oxygen species (ROS) production, and regulates matrix metalloproteinase (MMP) activity, which is vital for ECM remodeling and stabilization. IGF-1 deficiency, common in aging, compromises these protective mechanisms, increasing the risk of CMHs. This review explores the vasoprotective role of IGF-1 signaling in the cerebral microcirculation and its implications for preventing hypertension-induced CMHs in aging. Understanding and addressing the decline in IGF-1 signaling with age are crucial for maintaining cerebrovascular health and preventing hypertension-related vascular injuries in the aging population.

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.

Clinical Presentation and Imaging Findings of Irreversible Cerebral Amyloid Angiopathy-Related Inflammation (CAA-ri): A Case Report and Literature Review.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare condition primarily driven by an autoimmune reaction against cerebrovascular amyloid beta protein. Accurate diagnosis hinges on recognizing characteristic clinical symptoms and imaging features, such as asymmetric cerebral white matter lesions often linked to angioedema. We report the case of a woman in her 70s with progressive, irreversible CAA-ri who initially presented with left homonymous hemianopia and experienced significant psychiatric and neurological deterioration following an epileptic seizure. Despite initiating corticosteroid therapy seven months after onset, her condition continued to worsen, ultimately leading to her death in the 11th month due to general decline. This report reviews the clinical progression and imaging findings of the case, discusses the diagnostic process for CAA-ri, differentiates it from related conditions, and evaluates the timing of corticosteroid treatment.

Brain MRI in patients with V30M hereditary transthyretin amyloidosis.

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.

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.

Internal Cerebral Vein in Susceptibility-Weighted Imaging: A Reliable Tool to Differentiate Among Calcification, Microbleed, and Gross Hemorrhage in Brain Tumors.

Background and objective Susceptibility-weighted imaging (SWI) sequence is crucial for brain MRI examinations, as it is equipped with a high sensitivity to detect calcification, microbleed, and gross hemorrhage. Intracranial venous structures such as the superior sagittal sinus (SSS) and cortical veins are used as reference structures in phase image SWI to differentiate diamagnetic and paramagnetic substances. Our study focuses on the internal cerebral vein (ICV) as another reliable reference structure. We aimed to analyze the diagnostic accuracy and detectability of calcification and hemorrhagic components in brain tumors using ICV, cortical veins, and SSS as references on phase image SWI, with CT scans for comparison. Material and methods A retrospective review of calcification and hemorrhagic components in brain tumors was conducted using MRI and CT from January 2017 to June 2023. Results The study included a total of 192 patients with brain tumors. For calcification components (63 cases), ICV and cortical veins as reference structures showed excellent sensitivity (96.8%), specificity (100%), and accuracy (98.9%). SSS demonstrated slightly lower detectability but maintained high sensitivity (96.5%), specificity (100%), and accuracy (98.8%) levels. No statistical differences were noted among these reference structures (p>0.05) and excellent interobserver agreement (Cohen's Kappa of 1) was observed. Conclusions The ICV is located in the central image, is large, without any nearby arteries, and is easy to identify using SWI phase images. Using the ICV as a reference to characterize intratumoral calcification, microbleed, and hemorrhage demonstrates high accuracy and detectability. With its findings of excellent interobserver agreement, our study will be of immense benefit to radiologists.

Short-Term Neurologic Complications in Patients Undergoing Extracorporeal Membrane Oxygenation Support: A Review on Pathophysiology, Incidence, Risk Factors, and Outcomes.

Regardless of the type, extracorporeal membrane oxygenation (ECMO) requires the use of large intravascular cannulas and results in multiple abnormalities including non-physiologic blood flow, hemodynamic perturbation, rapid changes in blood oxygen and carbon dioxide levels, coagulation abnormalities, and a significant systemic inflammatory response. Among other sequelae, neurologic complications are an important source of mortality and long-term morbidity. The frequency of neurologic complications varies and is likely underreported due to the high mortality rate. Neurologic complications in patients supported by ECMO include ischemic and hemorrhagic stroke, hypoxic brain injury, intracranial hemorrhage, and brain death. In addition to the disease process that necessitates ECMO, cannulation strategies and physiologic disturbances influence neurologic outcomes in this high-risk population. For example, the overall documented rate of neurologic complications in the venovenous ECMO population is lower, but a higher rate of intracranial hemorrhage exists. Meanwhile, in the venoarterial ECMO population, ischemia and global hypoperfusion seem to compose a higher percentage of neurologic complications. In what follows, the literature is reviewed to discuss the pathophysiology, incidence, risk factors, and outcomes related to short-term neurologic complications in patients supported by ECMO.

Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy.

Cerebral microhemorrhages (CMHs) are of paramount importance as they not only signify underlying vascular pathology but also have profound implications for cognitive function and neurological health, serving as a critical indicator for the early detection and management of vascular cognitive impairment (VCI). This study aimed to investigate the effects of hypertension-induced CMHs on gait dynamics in a mouse model, focusing on the utility of advanced gait metrics as sensitive indicators of subclinical neurological alterations associated with CMHs. To induce CMHs, we employed a hypertensive mouse model, using a combination of Angiotensin II and L-NAME to elevate blood pressure, further supplemented with phenylephrine to mimic transient blood pressure fluctuations. Gait dynamics were analyzed using the CatWalk system, with emphasis on symmetry indices for Stride Length (SL), Stride Time (ST), and paw print area, as well as measures of gait entropy and regularity. The study spanned a 30-day experimental period, capturing day-to-day variations in gait parameters to assess the impact of CMHs. Temporary surges in gait asymmetry, detected as deviations from median gait metrics, suggested the occurrence of subclinical neurological signs associated with approximately 50% of all histologically verified CMHs. Our findings also demonstrated that increases in gait entropy correlated with periods of increased gait asymmetry, providing insights into the complexity of gait dynamics in response to CMHs. Significant correlations were found between SL and ST symmetry indices and between these indices and the paw print area symmetry index post-hypertension induction, indicating the interdependence of spatial and temporal aspects of gait affected by CMHs. Collectively, advanced gait metrics revealed sensitive, dynamic alterations in gait regulation associated with CMHs, resembling the temporal characteristics of transient ischemic attacks (TIAs). This underscores their potential as non-invasive indicators of subclinical neurological impacts. This study supports the use of detailed gait analysis as a valuable tool for detecting subtle neurological changes, with implications for the early diagnosis and monitoring of cerebral small vessel disease (CSVD) in clinical settings.

Cerebral microbleeds: Causes, clinical relevance, and imaging approach - A narrative review.

With advances in magnetic resonance imaging (MRI) sequences, there has been increased identification of microbleed/microhemorrhage across different population ages, but more commonly in the older age group. These are defined as focal areas of signal loss on gradient echo MRI sequences (T2* and susceptibility-weighted images), which are usually <5 mm in size representing hemosiderin deposition with wide ranges of etiologies. Susceptibility-weighted imaging (SWI) has become a routine MRI sequence for practices across the globe resulting in better identification of these entities. Over the past decade, there has been a better understanding of the clinical significance of microbleeds including their prognostic value in ischemic and hemorrhagic stroke. Cerebral amyloid angiopathy and hypertension are the two most common causes of microbleeds following peripheral and central pattern, respectively. In the younger age group, microbleeds are more common due to familial conditions or a wide range of hypercoagulable states. This review outlines the pathophysiology, prevalence, and clinical implications of cerebral microhemorrhage along with a brief discussion about the technical considerations of SWI.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages.

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health.

Association Between Small Vessel Disease and Financial Capacity: A Study Based on Cognitively Normal Older Adults.

Background: Financial capacity is vital for the elderly, who possess a substantial share of global wealth but are vulnerable to financial fraud. Objective: We explored the link between small vessel disease (SVD) and financial capacity in cognitively unimpaired (CU) older adults via both cross-sectional and longitudinal analyses. Methods: 414 CU participants underwent MRI and completed the Financial Capacity Instrument-Short Form (FCI-SF). Subsequent longitudinal FCI-SF data were obtained from 104, 240, and 141 participants at one, two, and four years, respectively. SVD imaging markers, encompassing white matter hyperintensities (WMH), cerebral microbleeds (CMB), and lacune were evaluated. We used linear regression analyses to cross-sectionally explore the association between FCI-SF and SVD severity, and linear mixed models to assess how baseline SVD severity impacted longitudinal FCI-SF change. The false discovery rate method was used to adjust multiple comparisons. Results: Cross-sectional analysis revealed a significant association between baseline WMH and Bank Statement (BANK, ß=-0.194), as well as between lacune number and Financial Conceptual Knowledge (FC, ß= -0.171). These associations were stronger in APOE ɛ4 carriers, with ß= -0.282 for WMH and BANK, and ß= -0.366 for lacune number and FC. Longitudinally, higher baseline SVD total score was associated with severe FCI-SF total score decrease (ß= -0.335). Additionally, baseline WMH burden predicted future decreases in Single Checkbook/Register Task (SNG, ß= -0.137) and FC (ß= -0.052). Notably, the association between baseline WMH and SNG changes was amplified in APOE ɛ4 carriers (ß= -0.187). Conclusions: Severe SVD was associated with worse FCI-SF and could predict the decline of financial capacity in CU older adults.

Automated Detection of Cerebral Microbleeds on Two-dimensional Gradient-recalled Echo T2* Weighted Images Using a Morphology Filter Bank and Convolutional Neural Network.

PURPOSE: We present a novel algorithm for the automated detection of cerebral microbleeds (CMBs) on 2D gradient-recalled echo T2* weighted images (T2*WIs). This approach combines a morphology filter bank with a convolutional neural network (CNN) to improve the efficiency of CMB detection. A technical evaluation was performed to ascertain the algorithm's accuracy. METHODS: In this retrospective study, 60 patients with CMBs on T2*WIs were included. The gold standard was set by three neuroradiologists based on the Microbleed Anatomic Rating Scale guidelines. Images with CMBs were extracted from the training dataset comprising 30 cases using a morphology filter bank, and false positives (FPs) were removed based on the threshold of size and signal intensity. The extracted images were used to train the CNN (Vgg16). To determine the effectiveness of the morphology filter bank, the outcomes of the following two methods for detecting CMBs from the 30-case test dataset were compared: (a) employing the morphology filter bank and additional FP removal and (b) comprehensive detection without filters. The trained CNN processed both sets of initial CMB candidates, and the final CMB candidates were compared with the gold standard. The sensitivity and FPs per patient of both methods were compared. RESULTS: After CNN processing, the morphology-filter-bank-based method had a 95.0% sensitivity with 4.37 FPs per patient. In contrast, the comprehensive method had a 97.5% sensitivity with 25.87 FPs per patient. CONCLUSION: Through effective CMB candidate refinement with a morphology filter bank and FP removal with a CNN, we achieved a high CMB detection rate and low FP count. Combining a CNN and morphology filter bank may facilitate the accurate automated detection of CMBs on T2*WIs.

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.

Differences in lobar microbleed topography in cerebral amyloid angiopathy and hypertensive arteriopathy.

Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P < 0.001) than patients with hypertensive arteriolosclerosis. Strictly intracortical/juxtacortical lobar microbleeds were associated with CAA (OR 18.9 [1.9-191.4], P = 0.013), while the presence of subcortical lobar microbleeds was associated with hypertensive arteriolosclerosis (OR 10.9 [1.8-68.1], P = 0.010). Amyloid retention was higher in patients with strictly intracortical/juxtacortical CMBs than those without (SUVR = 1.15 [1.05-1.52] vs. 1.08 [1.02-1.19], P = 0.039). Amyloid retention positively correlated with the number of intracortical lobar microbleeds (P < 0.001) and negatively correlated with the number of subcortical lobar microbleeds (P = 0.018). CAA and cortical amyloid deposition are more strongly associated with strictly intracortical/juxtacortical microbleeds than subcortical lobar microbleeds. Categorization of lobar microbleeds based on anatomical location may help differentiate the underlying microangiopathy and potentially improve the accuracy of current neuroimaging criteria for cerebral small vessel disease.

Acute cerebral microbleeds detected on high resolution head CT presenting with transient neurologic events.

Introduction: Cerebral microbleeds (CMBs) are deposits of hemosiderin-laden macrophages that can be visualized on T2-weighted MRI sequences as small, ovoid areas of signal void. These markers represent hemorrhagic cerebral small vessel disease and are usually subclinical and asymptomatic. In these cases, we present two patients who presented with symptomatic, acute CMBs. Case description: Case 1 involves a 70-year-old male with history of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea. Five days prior to presentation, this patient reported a transient period of left upper extremity weakness. CT was performed and demonstrated a lesion on CT imaging consistent with an acute CMB in the R centrum semiovale.Case 2 describes an 82-year-old female with history of hypertension, remote large ischemic stroke, and post-stroke epilepsy. Patient described an episode of prolonged left sided shaking consistent with prior seizures despite her consistently taking anti-epileptic drugs. On CT, a small hyperdensity was seen in the R thalamus/internal capsule region consistent with acute CMB. Discussion: These two examples demonstrate acute CMBs causing patients to demonstrate symptoms mirroring those of a TIA and experience breakthrough seizures. A TIA would normally be an indication for antiplatelet therapy. Though prior reasoning warns against anticoagulation in patients with CMBs, recent works including the SPS3 (Shoamanesh et al., 2017) and WAKE-UP (Schlemm et al., 2022) trials both showed that the presence of CMB did not significantly affect outcomes after initiating antiplatelet therapy. One should adopt a more personalized approach when deciding the therapeutic intervention of choice in patients with prior CMB.

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.