Effect of Pulsatility on the Transport of Thrombin in an Idealized Cerebral Aneurysm Geometry

Computational models of cerebral aneurysm thrombosis are designed for use in research and clinical applications. A steady flow assumption is applied in many of these models. To explore the accuracy of this assumption a pulsatile-flow thrombin-transport computational fluid dynamics (CFD) model, which uses a symmetrical idealized aneurysm geometry, was developed. First, a steady-flow computational model was developed and validated using data from an in vitro experiment, based on particle image velocimetry (PIV). The experimental data revealed an asymmetric flow pattern in the aneurysm. The validated computational model was subsequently altered to incorporate pulsatility, by applying a data-derived flow function at the inlet boundary. For both the steady and pulsatile computational models, a scalar function simulating thrombin generation was applied at the aneurysm wall. To determine the influence of pulsatility on thrombin transport, the outputs of the steady model were compared to the outputs of the pulsatile model. The comparison revealed that in the pulsatile case, an average of 10.2% less thrombin accumulates within the aneurysm than the steady case for any given time, due to periodic losses of a significant amount of thrombin-concentrated blood from the aneurysm into the parent vessel’s bloodstream. These findings demonstrate that pulsatility may change clotting outcomes in cerebral aneurysms.

Indirect Flow Diversion for Off-Centered Bifurcation Aneurysms and Distant Small-Vessel Aneurysms, a Retrospective Proof of Concept Study From Five Neurovascular Centers

Background: Treatment of cerebral aneurysms using hemodynamic implants such as endosaccular flow disruptors and endoluminal flow diverters has gained significant momentum during recent years. The intended target zone of those devices is the immediate interface between aneurysm and parent vessel. The therapeutic success is based on the reduction of aneurysmal perfusion and the subsequent formation of a neointima along the surface of the implant. However, a subset of aneurysms–off-centered bifurcation aneurysms involving the origin of efferent branches and aneurysms arising from peripheral segments of small cerebral vessels–oftentimes cannot be treated via coiling or implanting a hemodynamic implant at the neck level for technical reasons. In those cases, indirect flow diversion–a flow diverter deployed in the main artery proximal to the parent vessel of the aneurysm–can be a viable treatment strategy, but clinical evidence is lacking in this regard.Materials and Methods: Five neurovascular centers contributed to this retrospective analysis of patients who were treated with indirect flow diversion. Clinical data, aneurysm characteristics, anti-platelet medication, and follow-up results, including procedural and post-procedural complications, were recorded.Results: Seventeen patients (mean age: 60.5 years, range: 35–77 years) with 17 target aneurysms (vertebrobasilar: n = 9) were treated with indirect flow diversion. The average distance between the flow-diverting stent and the aneurysm was 1.65 mm (range: 0.4–2.4 mm). In 15/17 patients (88.2%), perfusion of the aneurysm was reduced immediately after implantation. Follow-ups were available for 12 cases. Delayed opacification (OKM A3: 11.8%), reduction in size (OKM B1-3: 29.4%) and occlusion (D1: 47.1%) were observable at the latest investigation. Clinically relevant procedural complications and adverse events in the early phase and in the late subacute phase were not observed in any case.Conclusion: Our preliminary data suggest that indirect flow diversion is a safe, feasible, and effective approach to off-centered bifurcation aneurysms and distant small-vessel aneurysms. However, validation with larger studies, including long-term outcomes and optimized imaging, is warranted.

Sex Differences in Cerebral Aneurysms and Subarachnoid Hemorrhage

Sex differences in cerebral aneurysm occurrence and characteristics have been well described. Although sex differences in outcomes following ischemic stroke have been identified, the effect of sex on outcomes following hemorrhagic stroke, and in particular, aneurysm treatment has been less studied. We describe the current state of knowledge regarding the impact of sex on treatment and outcomes of cerebral aneurysms. Although prior studies suggest that aneurysm prevalence and progression may be related to sex, we did not find clear evidence that outcomes following subarachnoid hemorrhage vary based on sex. Last, we identify areas for future research that could enhance understanding of the role sex plays in this context.

Flow Diverter Device for Treatment of Cerebral Aneurysm with Short-Term Follow Up: Two Case Reports

The flow diverter device (FDD) is an important treatment method for cerebral aneurysms, especially for intracranial dissecting aneurysms. This paper is the result of FDD treatment for two cases of vertebral dissecting aneurysm (VADA) patients and short-term follow-up at 3 months. All two cases were targeted for unruptured cerebral aneurysm, and 4-vessel angiography was performed as a follow-up examination for 3 months after receiving the procedure. As result, it was possible to shorten the period of use of antiplatelet drugs. In the case of VADA, there are limitations in general coiling procedures or conventional surgical treatment methods. In that sense, the FDD treatment method can be a very effective alternative treatment of VADA

Clinical impact of Sim & Size® simulation software in the treatment of patients with cerebral aneurysms with flow-diverter Pipeline stents

Objectives This study evaluated the clinical impact of the Sim&Size® simulation software on the endovascular treatment with flow-diverter stents of patients with unruptured saccular intracranial aneurysms. Methods This monocentric retrospective study evaluated a cohort of patients treated with flow-divert stents between June 1, 2014, and December 31, 2019, for cerebral aneurysms. Patients belonged to two groups, patients treated with and without the Sim&Size® simulation software. Univariate, bivariate, and multivariate analyses were used to evaluate the clinical impact of simulation software. Results Out of the 73 interventions involving 68 patients analyzed by the study, 76.7% were simulated using the Sim&Size® simulation software, and 23.3% were not. Patients treated with the simulation software had shorter stent lengths (16.00 mm vs. 20.00 mm p-value = 0.001) and surgical time (100.00 min vs. 118.00 min p-value = 0.496). Also, fewer of them required more than one stent (3.6% vs. 17.6% p-value = 0.079). Three patients belonging to the non-stimulated group presented hemorrhagic complications. Conclusions Using the Sim&Size® simulation software for the endovascular treatment of intracranial aneurysms with pipeline flow-diverter stents reduces the stent length.

Using a Convolutional Neural Network and Convolutional Long Short-term Memory to Automatically Detect Aneurysms on 2D-DSA Images (Preprint)

BACKGROUND It is hard to distinguish cerebral aneurysms from overlapping vessels based on 2D DSA images due to their lack of spatial information. OBJECTIVE The aim of this study was to construct a deep learning diagnostic system to improve the ability to detect posterior communicating artery (PCoA) aneurysms on 2D-DSA images and validate the efficiency of the deep learning diagnostic system in 2D-DSA aneurysm detection. METHODS We proposed a two-stage detecting system. First, we established the regional localization stage (RLS) to automatically locate specific detection regions of raw 2D-DSA sequences. Then, in the intracranial aneurysm detection stage (IADS), we constructed the Bi-input+RetinaNet+C-LSTM framework to compare the performance of aneurysm detection with the existing three frameworks. Each of the frameworks had a fivefold cross-validation scheme. The area under the curve (AUC), the receiver operating characteristic (ROC) curve, and mean average precision (mAP) were used to validate the efficiency of different frameworks. The sensitivity, specificity and accuracy were used to identify the abilities of different frameworks. RESULTS A total of 255 patients with PCoA aneurysms and 20 patients without aneurysms were included in this study. The best AUC results of RetinaNet, RetinaNet+C-LSTM, Bi-input+RetinaNet and Bi-input+RetinaNet+C-LSTM were 0.95, 0.96, 0.92 and 0.97, respectively. The sensitivities of RetinaNet, RetinaNet+C-LSTM, Bi-input+RetinaNet, Bi-input+RetinaNet+C-LSTM, and human experts were 89.00% (67.02% to 98.43%), 88.00% (65.76% to 98.06%), 87.00% (64.53% to 97.66%), 89.00% (67.02% to 98.43%), and 90% (68.30% to 98.77%), respectively. The specificity of RetinaNet, RetinaNet+C-LSTM, Bi-input+RetinaNet, Bi-input+RetinaNet+C-LSTM, and human expert were 80.00% (56.34% to 94.27%), 89.00% (67.02% to 98.43%), 86.00% (63.31% to 97.24%), 93.00% (72.30% to 99.56%), and 90% (68.30% to 98.77%), respectively. The accuracies of RetinaNet, RetinaNet+C-LSTM, Bi-input+RetinaNet, Bi-input+RetinaNet+C-LSTM, and human experts were 84.50% (69.57% to 93.97%), 88.50% (74.44% to 96.39%), 86.50% (71.97% to 95.22%), 91.00% (77.63% to 97.72%), and 90.00% (76.34% to 97.21%), respectively. CONCLUSIONS A two-stage aneurysm detection system can reduce the time cost and the computational load. According to our results, more spatial and temporal information can help improve the performances of the frameworks so that Bi-input+RetinaNet+C-LSTM has the best performance compared to the other frameworks. Our study demonstrates that our system can assist doctors in detecting intracranial aneurysms on 2D-DSA images.

An Imbalance Between RAGE/MR/HMGB1 and ATP1α3 is Associated with Inflammatory Changes in Rat Brain Harboring Cerebral Aneurysms Prone to Rupture

Background and Purpose: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3).Methods: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet.Results: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05).Conclusion: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation

X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the SH2D1A/SAP gene. Loss or dysfunction of SH2D1A is associated with the inability in clearing Epstein-Barr-Virus (EBV) infections. Clinical manifestation is diverse and ranges from life-threatening hemophagocytic lymphohistiocytosis (HLH) and fulminant infectious mononucleosis (FIM) to lymphoma and antibody deficiency. Rare manifestations include aplastic anemia, chronic gastritis and vasculitis. Herein, we describe the case of a previously healthy eight-year old boy diagnosed with XLP1 presenting with acute non-EBV acute meningoencephalitis with thrombotic occlusive vasculopathy. The patient developed multiple cerebral aneurysms leading to repeated intracerebral hemorrhage and severe cerebral damage. Immunological examination was initiated after development of a susceptibility to infections with recurrent bronchitis and one episode of severe pneumonia and showed antibody deficiency with pronounced IgG1-3-4 subclass deficiency. We could identify a novel hemizygous SH2D1A point mutation affecting the start codon. Basal levels of SAP protein seemed to be detectable in CD8+ and CD4+ T- and CD56+ NK-cells of the patient what indicated an incomplete absence of SAP. In conclusion, we could demonstrate a novel SH2D1A mutation leading to deficient SAP protein expression and a rare clinical phenotype of non-EBV associated acute meningoencephalitis with thrombotic occlusive vasculopathy.

Pituitary Adenomas Associated with Intracranial Aneurysms: the Clinical Characteristics, Therapeutic Strategies, and Possible Effects of Vascular Remodeling Factors

Background Pituitary adenoma coexists with intracranial aneurysms in 2.3 to 3.6% of cases, and intracranial aneurysms are thought to be incidental. On the other hand, older age and cavernous sinus invasion are reported to increase the rate of coexistence, so these two diseases may be related. Methods Ten males and 14 females with the coexistence of pituitary adenomas and intracranial aneurysms were retrospectively investigated among 923 patients (2.6%). Patients were subdivided into two groups: those with direct attachment of cerebral aneurysms to the pituitary adenomas and those without direct attachment. The clinical characteristics, therapeutic strategies, and possible effects of vascular remodeling factors were investigated. Results Twelve patients had functioning pituitary adenomas, and cavernous sinus invasion was identified in 7 of 24 patients. Five of these 7 patients were treated with priority for the cerebral aneurysm until 2007, whereas 14 of 17 patients without involvement of the aneurysm tip in the tumor were treated with priority for the pituitary adenoma in the later period. Among vascular remodeling factors, strong expression of vascular endothelial growth factor (VEGF) was significantly associated with the coexistence of pituitary adenoma and cerebral aneurysm (p < 0.05). Conclusion Intracranial aneurysms were found to coexist in 2.6% of cases of surgically treated pituitary adenomas. VEGF-induced arterial wall remodeling may be part of the mechanism of association between pituitary adenomas and cerebral aneurysms, suggesting possible causative mechanism.