Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

Estimating Bridge Natural Frequencies Based on Modal Analysis of Vehicle-Bridge Synchronized Vibration Data.

This paper presents a method for accurately estimating the natural frequencies of bridges by simultaneously measuring the acceleration vibration data of vehicles and bridges and applying modal analysis theory. Vibration sensors synchronized with GPS timing were installed on both vehicles and bridges, achieving stable and high-precision time synchronization. This enabled the computation of the bridge's Frequency Response Functions (FRFs) for each mode, leading to a refined estimation of natural frequencies. The validity of the theory was confirmed through numerical simulations and experimental tests. The simulations confirmed its effectiveness, and similar trends were observed in actual bridge measurements. Consequently, this method significantly enhances the feasibility of bridge health monitoring systems. The proposed method is suitable for road bridges with spans ranging from short- to medium-span length, where the vehicle is capable of exciting the bridge.

Water content for clot composition prediction in acute ischemic stroke.

BACKGROUND: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. MATERIALS AND METHODS: This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. RESULTS: The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion.

Clinical presentation and treatment of 26 spinal epidural arteriovenous fistulas: a single-center experience.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are rarely diagnosed vascular malformations that can cause spinal cord compression and congestive myelopathy. METHODS: This is a single-center, retrospective case series of patients with SEDAVFs who underwent observation or treatment at UCLA medical center between 1993 and 2023. RESULTS: Between 1993 and 2023 a total of 26 patients at UCLA were found to have a SEDAVF. The median age at treatment was 59 years (range 4 months to 91 years). Compared with sacral, lumbar, and thoracic SEDAVFs, patients with cervical SEDAVF were younger (41 years vs 63 years, P=0.016) and more likely to be female (66.7% vs 14.3%, P=0.006). Possible triggers for development of SEDAVFs may be prior spinal surgery or trauma (n=4), turning the neck (n=1), lifting a heavy box (n=1), a prolonged period of bending over (n=1), and neurofibromatosis type 1 (n=1). Of the 22 patients treated endovascularly, 18 (82%) were angiographically cured on the first attempt without complications. One patient underwent surgical treatment alone and had a failed surgery on the first attempt, and developed a surgical site infection after the second successful attempt at treatment. Of the 16 patients with adequate clinical follow-up, 11 (69%) demonstrated early improved clinical outcome (eg, improved strength on examination, absent bruit). CONCLUSIONS: SEDAVFs are a rarely diagnosed disease that can be treated effectively and safely with endovascular embolization in most cases. Patients with sacral, lumbar, and thoracic SEDAVFs were older and more often male compared to patients with cervical SEDAVFs.

Endothelial Cell Transcription Modulation in Cerebral Aneurysms After Endovascular Flow Diversion.

PURPOSE: Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity. METHODS: Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed. RESULTS: Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding. CONCLUSION: Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome.

Investigator-initiated clinical trial of stabilizer device: A novel intracranial exchange guidewire for neuroendovascular treatments.

BACKGROUND: Neuroendovascular procedures, especially those involving significant vessel tortuosity, giant intracranial aneurysms, or distally located lesions, frequently necessitate exchange methods. However, exchange maneuvers pose a risk of inadvertent vessel injury. To address these challenges, a Stabilizer device was developed and evaluated for its efficacy and safety. This clinical trial aimed to assess the efficacy and safety of the Stabilizer device in facilitating the navigation of neuroendovascular devices to target lesions in cases where the exchange technique was necessary. METHODS: This was a single-arm, prospective, open-label, multicenter clinical trial performed at nine different sites. It focused on investigating the use of the Stabilizer device for treating intracranial aneurysms and atherosclerosis. RESULTS: A total of 31 patients were enrolled across nine centers in Japan from July 21, 2022, to March 10, 2023. The study enrolled 24 (77.4%) patients with intracranial aneurysms and seven (22.6%) patients with intracranial artery stenosis. Majority of the target lesions were in the middle cerebral artery territory (83.9%). The Stabilizer device was used to exchange for 0.027-inch catheters, intermediate catheters, PTA balloons, and Wingspan stent system. The Stabilizer device demonstrated 100% technical success rate. While three complications related to the treatment were noted, there were no complications related to the device, including any vascular damage. CONCLUSIONS: This is the first multicenter clinical trial that investigated and demonstrated technical efficacy as well as overall safety profile of the Stabilizer device in neuroendovascular procedures where the use of an exchange method was necessary.