Citations

Background: Real world studies of silent brain infarction (SBI) and white matter disease (WMD) are impeded by challenges in cohort identification. Natural language processing (NLP) from imaging reports may facilitate future studies. However, electronic health records can be heterogeneous and the process of interpreting neuroimages and generating reports can vary. Understanding knowledge representation and relationships between neuroimages and imaging reports is crucial for using NLP to facilitate disease management and cohort identification. Methods: A balanced sample of head neuroimages (CT, MRI) of patients >50 years without clinical histories of symptomatic stroke, TIA, or dementia were obtained at Mayo Clinic and Tufts Medical Center. A team of 4 radiology residents performed report interpretation (RI) on 1000 reports according to a standardized protocol for the presence of SBIs, the presence of WMD, and WMD grade. A random subsample of 400 was doubly read for interrater reliability. For benchmarking, a team of 4 neuroradiologists directly reviewed and described findings on a subsample of 182 images, each doubly read. We assessed interrater reliability for direct review (DR) and RI, and agreement between these 2 information sources. An NLP algorithm was developed to review and extract findings from 1000 imaging reports. Results: For DR, interrater reliability was moderate for SBIs and WMD (k = 0.53, 95% CI 0.43-0.64 and k = 0.47, 95% CI 0.33-0.61) and good for WMD grade (Spearman 0.71, p<0.001). For RI, interrater reliability for SBIs, WMD and WMD grade was good (k = 0.88, 95% CI 0.80-0.97; k = 0.98, 95% CI 0.97-1.00; and Spearman = 0.985, p<0.001, respectively). Agreement between DR and RI was good for SBIs (k = 0.77, 95% CI 0.67-0.86) and WMD (k = 0.65, 95% CI 0.54-0.77). Spearman rank correlations comparing WMD grade interpretation DR to RI was 0.60 (p<0.001). In identifying the presence of SBIs and WMDs, the accuracy of the NLP algorithm was 0.991 and 0.994, respectively. Conclusion: For the presence of SBI and WMD, and WMD grade, agreement between RI and DR was similar to agreement between 2 neuroradiologists directly reviewing neuroimages. It is highly feasible to use NLP to identify patients with SBIs and WMDs for clinical studies.

Purpose: Endovascular occlusion of aneurysms with the use of detachable platinum coils has proved to be a safe and durable alternative to the traditional surgical clipping. The aim of the present study is to understand the mechanism of apoptosis in aneurysm embolized with platinum coils using rabbit elastase‐induced aneurysm model. Materials & Methods: Elastase‐induced saccular aneurysms were created at the origin of right common carotid artery in thirty rabbits. Aneurysms were allowed to mature for 8 weeks then 20 aneurysms were embolized using platinum coils by endovascular means. Ten uncoiled aneurysms were used as controls. After 2 weeks (n=10) and 4 weeks (n=10) of implantation, aneurysm samples were harvested for apoptotic studies. Results: Expression of pro‐caspases‐3, ‐8 and ‐9 were elevated in coiled aneurysm embolized with platinum coils at both time points when compared with uncoiled aneurysm and control left carotid artery. Cleaved caspases‐3, ‐8 and ‐9 were found to be expressed only at 4 weeks after embolization. Cells within aneurysm cavity were TUNEL positive at 4 weeks only. Expression of tumor necrosis‐&#945; (TNF‐&#945;) was high in coiled aneurysm when compared with controls. There was no significant difference in the expression of Fas‐ligand among groups. Decreased expression of antiapoptotic protein, Bcl‐2, and increased expression of proapoptotic proteins, Bad, Bax and Bid, were observed in coiled aneurysms at both time points. Conclusion: Activation apoptosis in aneurysms after embolization with platinum coils is mediated by both TNF‐&#945; mediated‐extrinsic and Bcl‐2 mediated‐intrinsic pathway.

The purpose of the study was to test the hypothesis that systemic administration of vitamin C, through its action of stimulating collagen synthesis and crosslinking, would improve the healing response in experimental aneurysms treated with platinum coil embolization. Nineteen experimental aneurysms in rabbits were embolized with platinum coils (>30% packing density). Animals were divided into three groups. Group 1 (n=6) rabbits served as controls, Group 2 (n=5) rabbits were fed with a vitamin C‐supplemented feed and Group 3 (n=8) rabbits were medicated with vitamin C pills. Subjects were euthanized at 12 weeks following coil implantation and serum vitamin C levels were measured. Digital subtraction angiography was used to evaluate stability after embolization. Histological samples were examined with a grading system (range, 0–12) based on the neck and dome features. Masson Trichrome was employed to evaluate the collagen deposition. One‐way analysis of variance was used to test the significance in histological healing and angiographic measurements between groups. There were no significant differences between groups in aneurysm size or angiographic findings. Mean serum vitamin C concentration was significantly higher in Group 3 (45.4±9.0 mM) and Group 2 (38.6±8.9 mM) compared to Group 1 (21.1±3.6 mM). There was no statistically significant change in the level of vitamin C between Group 2 and Group 3. There was no significant difference in histological scores or collagen deposition among groups. Our results suggest that vitamin C supplementation following platinum coil embolization may not improve long‐term cerebral aneurysm. This study was supported by the American Heart Association (09SDG2160146‐01).

Background Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model. Methods FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH. Results Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively). Conclusion These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Introduction There is increased interest in the use of artificial intelligence-based (AI) software packages in the evaluation of neuroimaging studies for acute ischemic stroke. We studied whether, compared to standard image interpretation without AI, Brainomix e-ASPECTS software improved interobserver agreement and accuracy in detecting ASPECTS regions affected in anterior circulation LVO. Methods We included 60 consecutive patients with anterior circulation LVO who had TICI 3 revascularization within 60 minutes of their baseline CT. A total of 16 readers, including senior neuroradiologists, junior neuroradiologists and vascular neurologists participated. Readers interpreted CT scans on independent workstations and assessed final ASPECTS and evaluated whether each individual ASPECTS region was affected. Two months later, readers again evaluated the CT scans, but with assistance of e-ASPECTS software. We assessed interclass correlation coefficient for total ASPECTS and interobserver agreement with Fleiss’ Kappa for each ASPECTS region with and without assistance of the e-ASPECTS. We also assessed accuracy for the readers with and without e-ASPECTS assistance. In our assessment of accuracy, ground truth was the 24 hour CT in this cohort of patients who had prompt and complete revascularization. Results Interclass correlation coefficient for total ASPECTS without e-ASPECTS assistance was 0.395, indicating fair agreement compared, to 0.574 with e-ASPECTS assistance, indicating good agreement (P < 0.01). There was significant improvement in inter-rater agreement with e-ASPECTS assistance for each individual region with the exception of M6 and caudate. The e-ASPECTS software had higher accuracy than the overall cohort of readers (with and without e-ASPECTS assistance) for every region except the caudate. Conclusions Use of Brainomix e-ASPECTS software resulted in significant improvements in inter-rater agreement and accuracy of ASPECTS score evaluation in a large group of neuroradiologists and neurologists. e-ASPECTS software was more predictive of final infarct/ASPECTS than the overall group interpreting the CT scans with and without e-ASPECTS assistance.

Background and aim Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

Background Diffuse intracranial susceptibility abnormalities have recently been described among patients with coronavirus disease 2019 (COVID-19), although prior studies have consisted of case reports and/or series. This brief literature review seeks to compile and catalogue the available data to elucidate characteristic features of such findings. Materials and methods Scientific articles and studies on intracranial microhemorrhages in the setting of COVID-19 were searched on PubMed, Google Scholar, and the Cochrane Library. Included studies described intracranial microbleed(s) on magnetic resonance imaging in patients with COVID-19. If multiple patients were described, only patients with intracranial microhemorrhage on magnetic resonance imaging were included for analysis. Patient demographics, severity of illness (e.g. intensive care unit admission and/or intubation), time from diagnosis of COVID-19 to magnetic resonance imaging, and location(s) of any observed microhemorrhages were noted. Results A total of 39 patients with suspected intracranial microhemorrhages have been described in prior studies. The average age of patients was 64.7 years; 21.9% were women. The average time between COVID-19 diagnosis and magnetic resonance imaging was 31.7 days. All patients in the cohort were admitted to critical care and were either intubated or treated with extracorporeal membrane oxygenation during their clinical course. Microhemorrhages were most commonly located in the subcortical/juxtacortical white matter and corpus callosum. Conclusions Intracranial microbleeds are a well-documented finding in patients with severe COVID-19, and are most commonly callosal and subcortical/juxtacortical in location.

Preclinical testing platforms have been instrumental in the research and development of thrombectomy devices. However, there is no single model which fully captures the complexity of cerebrovascular anatomy, physiology, and the dynamic artery-clot-device interaction. This article provides a critical review of phantoms, in-vivo animal, and human cadaveric models used for thrombectomy testing and provides insights into the strengths and limitations of each platform. Articles published in the past 10 years that reported thrombectomy testing platforms were identified. Characteristics of each test platform, such as intracranial anatomy, artery tortuosity, vessel friction, flow conditions, device-vessel interaction, and visualization, were captured and benchmarked against human cerebral vessels involved in large-vessel occlusion stroke. Thrombectomy phantoms have been constructed from silicone, direct 3D-printed polymers, and glass. These phantoms represent oversimplified patient-specific cerebrovascular geometry but enable adequate visualization of devices and clots under appropriate flow conditions. They do not realistically mimic the artery-clot interaction. For the animal models, arteries from swine, canines, and rabbits have been reported. These models can reasonably replicate the artery-clot-device interaction and have the unique value of evaluating the safety of thrombectomy devices. However, the vasculature geometries are substantially less complex and flow conditions are different from human cerebral arteries. Cadaveric models are the most accurate vascular representations but with limited access and challenges in reproducibility of testing conditions. Multiple test platforms should be likely used for comprehensive evaluation of thrombectomy devices. Interpretation of the testing results should take into consideration platform-specific limitations.