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Yiemeng Hoi, Hui Meng, Scott H. Woodward, Bernard R. Bendok, Ricardo A. Hanel, Lee R. Guterman and L. Nelson Hopkins

Object. Few researchers have quantified the role of arterial geometry in the pathogenesis of saccular cerebral aneurysms. The authors investigated the effects of parent artery geometry on aneurysm hemodynamics and assessed the implications relative to aneurysm growth and treatment effectiveness.

Methods. The hemodynamics of three-dimensional saccular aneurysms arising from the lateral wall of arteries with varying arterial curves (starting with a straight vessel model) and neck sizes were studied using a computational fluid dynamics analysis. The effects of these geometric parameters on hemodynamic parameters, including flow velocity, aneurysm wall shear stress (WSS), and area of elevated WSS during the cardiac cycle (time-dependent impact zone), were quantified. Unlike simulations involving aneurysms located on straight arteries, blood flow inertia (centrifugal effects) rather than viscous diffusion was the predominant force driving blood into aneurysm sacs on curved arteries. As the degree of arterial curvature increased, flow impingement on the distal side of the neck intensified, leading to elevations in the WSS and enlargement of the impact zone at the distal side of the aneurysm neck.

Conclusions. Based on these simulations the authors postulate that lateral saccular aneurysms located on more curved arteries are subjected to higher hemodynamic stresses. Saccular aneurysms with wider necks have larger impact zones. The large impact zone at the distal side of the aneurysm neck correlates well with other findings, implicating this zone as the most likely site of aneurysm growth or regrowth of treated lesions. To protect against high hemodynamic stresses, protection of the distal side of the aneurysm neck from flow impingement is critical.

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Jingyu Chen, Zhi Chen, Fei Li, Jiangkai Lin, Hui Meng and Hua Feng

Object

The purpose of this study was to review 14 rare cases of cerebral paragonimiasis that first manifested as intracranial hemorrhage (ICH), and to investigate the characteristics of clinical manifestation, diagnosis, and treatment of the disease.

Methods

The authors have encountered 14 cases of cerebral paragonimiasis in patients between the ages of 6 and 16 years (mean age 11.5 years) who presented with sudden headache, nausea, and vomiting. Three of them were affected with varying degrees of limb hemiplegia, and in 1 this was combined with high fever; the blood eosinophil count and enzyme-linked immunosorbent assay showed positive results too. The ICHs were observed with cranial CT and MR imaging, and lung lesions were also detected in 5 cases on chest CT scans. Ten of the diagnosed cases were treated with oral praziquantel. Three of these patients were given carbamazepine from the beginning of parasiticidal treatment to prevent seizures; 4 of the remaining 7 patients experienced epileptic seizures during the treatment process. Four patients needed surgery to remove the lesions, and these individuals received praziquantel treatment right after the surgery.

Results

Pathological examinations demonstrated eosinophilic granuloma in these patients. There was no disease recurrence or epilepsy in 11–40 months of follow-up; however, mild hemiplegia could still be observed in 2 cases after 12 months and 17 months of follow-up.

Conclusions

The possibility of cerebral paragonimiasis should be considered when ICH is detected in young patients who are either from an endemic area or have recently visited such an area; the relatively small amount of hemorrhage in cerebral paragonimiasis is often represented as small lesions surrounded by disproportionately larger edema on the imaging study. Preventive antiepileptic drugs should be used along with the administration of parasiticide.

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Nikhil Paliwal, Prakhar Jaiswal, Vincent M. Tutino, Hussain Shallwani, Jason M. Davies, Adnan H. Siddiqui, Rahul Rai and Hui Meng

OBJECTIVE

Flow diverters (FDs) are designed to occlude intracranial aneurysms (IAs) while preserving flow to essential arteries. Incomplete occlusion exposes patients to risks of thromboembolic complications and rupture. A priori assessment of FD treatment outcome could enable treatment optimization leading to better outcomes. To that end, the authors applied image-based computational analysis to clinically FD-treated aneurysms to extract information regarding morphology, pre- and post-treatment hemodynamics, and FD-device characteristics and then used these parameters to train machine learning algorithms to predict 6-month clinical outcomes after FD treatment.

METHODS

Data were retrospectively collected for 84 FD-treated sidewall aneurysms in 80 patients. Based on 6-month angiographic outcomes, IAs were classified as occluded (n = 63) or residual (incomplete occlusion, n = 21). For each case, the authors modeled FD deployment using a fast virtual stenting algorithm and hemodynamics using image-based computational fluid dynamics. Sixteen morphological, hemodynamic, and FD-based parameters were calculated for each aneurysm. Aneurysms were randomly assigned to a training or testing cohort in approximately a 3:1 ratio. The Student t-test and Mann-Whitney U-test were performed on data from the training cohort to identify significant parameters distinguishing the occluded from residual groups. Predictive models were trained using 4 types of supervised machine learning algorithms: logistic regression (LR), support vector machine (SVM; linear and Gaussian kernels), K-nearest neighbor, and neural network (NN). In the testing cohort, the authors compared outcome prediction by each model trained using all parameters versus only the significant parameters.

RESULTS

The training cohort (n = 64) consisted of 48 occluded and 16 residual aneurysms and the testing cohort (n = 20) consisted of 15 occluded and 5 residual aneurysms. Significance tests yielded 2 morphological (ostium ratio and neck ratio) and 3 hemodynamic (pre-treatment inflow rate, post-treatment inflow rate, and post-treatment aneurysm averaged velocity) discriminants between the occluded (good-outcome) and the residual (bad-outcome) group. In both training and testing, all the models trained using all 16 parameters performed better than all the models trained using only the 5 significant parameters. Among the all-parameter models, NN (AUC = 0.967) performed the best during training, followed by LR and linear SVM (AUC = 0.941 and 0.914, respectively). During testing, NN and Gaussian-SVM models had the highest accuracy (90%) in predicting occlusion outcome.

CONCLUSIONS

NN and Gaussian-SVM models incorporating all 16 morphological, hemodynamic, and FD-related parameters predicted 6-month occlusion outcome of FD treatment with 90% accuracy. More robust models using the computational workflow and machine learning could be trained on larger patient databases toward clinical use in patient-specific treatment planning and optimization.

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Jianping Xiang, Robert J. Damiano, Ning Lin, Kenneth V. Snyder, Adnan H. Siddiqui, Elad I. Levy and Hui Meng

OBJECT

Flow diversion via Pipeline Embolization Device (PED) represents the most recent advancement in endovascular therapy of intracranial aneurysms. This exploratory study aims at a proof of concept for an advanced device-modeling tool in conjunction with computational fluid dynamics (CFD) to evaluate flow modification effects by PED in actual, treated cases.

METHODS

The authors performed computational modeling of 3 PED-treated complex aneurysm cases. The patient in Case 1 had a fusiform vertebral aneurysm treated with a single PED. In Case 2 the patient had a giant internal carotid artery (ICA) aneurysm treated with 2 PEDs. Case 3 consisted of tandem ICA aneurysms (III-a and III-b) treated by a single PED. The authors’ recently developed high-fidelity virtual stenting (HiFiVS) technique was used to recapitulate the clinical deployment process of PEDs in silico for these 3 cases. Pretreatment and posttreatment aneurysmal hemodynamics studies performed using CFD simulation were analyzed. Changes in aneurysmal flow velocity, inflow rate, wall shear stress (WSS), and turnover time were calculated and compared with the clinical outcome.

RESULTS

In Case 1 (occluded within the first 3 months), the aneurysm had the most drastic flow reduction after PED placement; the aneurysmal average velocity, inflow rate, and average WSS were decreased by 76.3%, 82.5%, and 74.0%, respectively, whereas the turnover time was increased to 572.1% of its pretreatment value. In Case 2 (occluded at 6 months), aneurysmal average velocity, inflow rate, and average WSS were decreased by 39.4%, 38.6%, and 59.1%, respectively, and turnover time increased to 163.0%. In Case 3, Aneurysm III-a (occluded at 6 months) had a decrease by 38.0%, 28.4%, and 50.9% in average velocity, inflow rate, and average WSS, respectively, and turnover time increased to 139.6%, which was quite similar to Aneurysm II. Surprisingly, the adjacent Aneurysm III-b had more substantial flow reduction (a decrease by 77.7%, 53.0%, and 84.4% in average velocity, inflow rate, and average WSS, respectively, and an increase to 213.0% in turnover time) than Aneurysm III-a, which qualitatively agreed with angiographic observation at 3-month follow-up. However, Aneurysm III-b remained patent at both 6 months and 9 months. A closer examination of the vascular anatomy in Case 3 revealed blood draining to the ophthalmic artery off Aneurysm III-b, which may have prevented its complete thrombosis.

CONCLUSIONS

This proof-of-concept study demonstrates that HiFiVS modeling of flow diverter deployment enables detailed characterization of hemodynamic alteration by PED placement. Posttreatment aneurysmal flow reduction may be correlated with aneurysm occlusion outcome. However, predicting aneurysm treatment outcome by flow diverters also requires consideration of other factors, including vascular anatomy.

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Yiemeng Hoi, Ling Gao, Markus Tremmel, Rocco A. Paluch, Adnan H. Siddiqui, Hui Meng and J Mocco

Object

Pathological extremes in cerebrovascular remodeling may contribute to basilar artery (BA) dolichoectasia and fusiform aneurysm development. Factors regulating cerebrovascular remodeling are poorly understood. To better understand hemodynamic influences on cerebrovascular remodeling, we examined BA remodeling following common carotid artery (CCA) ligation in an animal model.

Methods

Rabbits were subjected to sham surgery (3 animals), unilateral CCA ligation (3 animals), or bilateral CCA ligation (5 animals). Transcranial Doppler ultrasonography and rotational angiography were used to compute BA flow, diameter, wall shear stress (WSS), and a tortuosity index on Days 0, 1, 4, 7, 14, 28, 56, and 84. Basilar artery tissues were stained and analyzed at Day 84. Statistical analysis was performed using orthogonal contrast analysis, repeated measures analysis of variance, or mixed regression analysis of repeated measures. Statistical significance was defined as a probability value < 0.05.

Results

Basilar artery flow and diameter increased significantly after the procedure in both ligation groups, but only the bilateral CCA ligation group demonstrated significant differences between groups. Wall shear stress significantly increased only in animals in the bilateral CCA ligation group and returned to baseline by Day 28, with 52% of WSS correction occurring by Day 7. Only the bilateral CCA ligation group developed significant BA tortuosity, occurring within 7 days postligation. Unlike the animals in the sham and unilateral CCA ligation groups, the animals in the bilateral CCA ligation group had histological staining results showing a substantial internal elastic lamina fragmentation.

Conclusions

Increased BA flow results in adaptive BA remodeling until WSS returns to physiological baseline levels. Morphological changes occur rapidly following flow alteration and do not require chronic insult to affect substantial and significant structural transformation. Additionally, it appears that there exists a flow-increase threshold that, when surpassed, results in significant tortuosity.

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Hui Meng, Eleni Metaxa, Ling Gao, Nicholas Liaw, Sabareesh K. Natarajan, Daniel D. Swartz, Adnan H. Siddiqui, John Kolega and J Mocco

Object

Hemodynamic insult has been speculated to be a key factor in intracranial aneurysm formation; however, it is unclear whether a sustained insult is necessary. The authors examined whether aneurysmal degradation would continue despite the normalization of wall shear stress (WSS) by adaptive outward vascular remodeling.

Methods

Twenty-five rabbits underwent either sham operation (5 animals) or bilateral common carotid artery ligation (20 animals) to augment basilar artery (BA) flow. Basilar termini (BTs) were harvested at 5 days and 3, 12, and 27 weeks postoperation. Histological changes at the BTs were quantified using an aneurysm development score (ADS) wherein the luminal length of the vessel wall exhibiting internal elastic lamina (IEL) loss, media thinning (> 30% media loss), and bulging was multiplied by the percentage of media thinning divided by the BA diameter. This score and its component variables were evaluated over the specified time points and compared with the WSS time course obtained from multiple angiography and BA flow velocity measurements.

Results

Serial examination of histological sections from the ligation group (17 rabbits survived the procedure) demonstrated localized, progressive, degenerative, and aneurysmal changes at the BTs. Prominent IEL loss was observed in BT specimens from all ligated animals. Media thinning and luminal bulging significantly progressed over the 27-week follow-up. The composite ADS significantly increased over the study period, indicating progressive aneurysm development, although the WSS returned to preligation baseline values within 5 weeks of ligation.

Conclusions

Hemodynamic insult can elicit a pathological vascular response leading to a self-sustaining aneurysmal remodeling that does not require persistence of the original inciting factor to continue its pathological progression.

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Hamidreza Rajabzadeh-Oghaz, Muhammad Waqas, Sricharan S. Veeturi, Kunal Vakharia, Michael K. Tso, Kenneth V. Snyder, Jason M. Davies, Adnan H. Siddiqui, Elad I. Levy and Hui Meng

OBJECTIVE

Previous studies have found that ruptured intracranial aneurysms (RIAs) have distinct morphological and hemodynamic characteristics, including higher size ratio and oscillatory shear index and lower wall shear stress. Unruptured intracranial aneurysms (UIAs) that possess similar characteristics to RIAs may be at a higher risk of rupture than those UIAs that do not. The authors previously developed the Rupture Resemblance Score (RRS), a data-driven computer model that can objectively gauge the similarity of UIAs to RIAs in terms of morphology and hemodynamics. The authors aimed to explore the clinical utility of RRS in guiding the management of UIAs, especially for challenging cases such as small UIAs.

METHODS

Between September 2018 and June 2019, the authors retrospectively collected consecutive challenging cases of incidentally identified UIAs that were discussed during their weekly multidisciplinary neurovascular conference. From patient 3D digital subtraction angiography, they reconstructed the aneurysm geometry and performed computer-assisted 3D morphology analysis and computational fluid dynamics simulation. They calculated RRS for every UIA case and compared it against the treatment decision made at the neurovascular conference as well as the recommendation based on the unruptured intracranial aneurysm treatment score (UIATS).

RESULTS

Forty-seven patients with 79 UIAs, 90% of which were < 7 mm in size, were included in this study. The mean RRS (range 0.0–1.0) was 0.24 ± 0.31. At the conferences, treatment was endorsed for 45 of the UIAs (57%). These cases had significantly higher RRSs than the 34 cases suggested for observation (0.33 ± 0.34 vs 0.11 ± 0.19, p < 0.001). The UIATS-based recommendations were “observation” for 24 UIAs (30%), “treatment” for 21 UIAs (27%), and “not definitive” for 34 UIAs (43%). These “not definitive” cases were stratified by RRS based on similarity to RIAs.

CONCLUSIONS

Although not a rupture predictor, RRS is a data-driven model that gauges the similarity of UIAs to RIAs in terms of morphology and hemodynamics. In cases in which the UIATS-based recommendation is not definitive, RRS provides additional stratification to assist the identification of high-risk UIAs. The current study highlights the clinical utility of RRS in a real-world setting as an adjunctive tool for the management of UIAs.