Cranial nerve deficits in giant cavernous carotid aneurysms and their relation to aneurysm morphology and location.

BACKGROUND: Giant cavernous carotid aneurysms (GCCAs) usually exert substantial mass effect on adjacent intracavernous cranial nerves. Since predictors of cranial nerve deficits (CNDs) in patients with GCCA are unknown, we designed a study to identify associations between CND and GCCA morphology and the location of mass effect. METHODS: This study was based on data from the prospective clinical and imaging databases of the Giant Intracranial Aneurysm Registry. We used magnetic resonance imaging and digital subtraction angiography to examine GCCA volume, presence of partial thrombosis (PT), GCCA origins, and the location of mass effect. We also documented whether CND was present. RESULTS: We included 36 GCCA in 34 patients, which had been entered into the registry by eight participating centers between January 2009 and March 2016. The prevalence of CND was 69.4%, with one CND in 41.7% and more than one in 27.5%. The prevalence of PT was 33.3%. The aneurysm origin was most frequently located at the anterior genu (52.8%). The prevalence of CND did not differ between aneurysm origins (p = 0.29). Intracavernous mass effect was lateral in 58.3%, mixed medial/lateral in 27.8%, and purely medial in 13.9%. CND occurred significantly more often in GCCA with lateral (81.0%) or mixed medial/lateral (70.0%) mass effect than in GCCA with medial mass effect (20.0%; p = 0.03). After adjusting our data for the effects of the location of mass effect, we found no association between the prevalence of CND and aneurysm volume (odds ratio (OR) 1.30 (0.98-1.71); p = 0.07), the occurrence of PT (OR 0.64 (0.07-5.73); p = 0.69), or patient age (OR 1.02 (95% CI 0.95-1.09); p = 0.59). CONCLUSIONS: Distinguishing between medial versus lateral location of mass effect may be more helpful than measuring aneurysm volumes or examining aneurysm thrombosis in understanding why some patients with GCCA present with CND while others do not. CLINICAL TRIAL REGISTRATION NO: NCT02066493 ( clinicaltrials.gov ).

The Dural AV-Fistula (DAVF), the Most Frequent Acquired Vascular Malformation of the Central Nervous System (CNS).

Acquired arteriovenous malformations, such as is the case with dural arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial ingrowth into venous spaces that reaches directly the venous lumen, without interposition of a capillary network, thereby creating an AV-shunt.The following concise text will provide elements in regards to diagnosis, indication for treatment discussion and choice of endovascular treatment (EVT) method.

Intra-aneurysmal pressure and flow changes induced by flow diverters: relation to aneurysm size and shape.

BACKGROUND AND PURPOSE: Effects of blood flow modification by flow diverters are observed to lead often to aneurysm thrombosis and reverse remodeling. For this process, to further understand the potential roles of intra-aneurysmal blood pressure changes and aneurysm morphologies, 23 patients were studied by numeric simulation. MATERIALS AND METHODS: 3D imaging of aneurysms of different sizes and shapes, all located at the supraclinoid segment of the ICA (n=23), was prepared for CFD simulations. Hemodynamic variables were calculated for conditions before and after virtual FD implantation, reconstituting a vessel wall scaffold across the aneurysm neck. WSS, velocity, residence time, turnover time, and intra-aneurysmal pressure were assessed statistically. RESULTS: After placement of FDs, significant reductions inside the aneurysm were observed for most hemodynamic variables (P<.01) except mean intra-aneurysmal pressures. For minimum/maximum intra-aneurysmal pressure values, small but significant changes were found; however, they were considered too small to be of relevance. CONCLUSIONS: Calculations in 23 cases did not reveal significant intra-aneurysmal mean or peak pressure changes, indicating a minor role of pressure changes in the rare event of secondary ruptures after FD use. Other hemodynamic variables (WSS and velocity) exhibited more significant changes, indicating their role in intra-aneurysmal thrombus formation. Size-dependent, significantly higher reduction in WSS (P=.069) and velocity (P=.013) was observed in small aneurysms compared with larger ones. When it came to shape, there were significantly higher reductions in WSS (P=.055) and velocity (P=.065) and a significantly higher increase in turnover time in fusiform aneurysms compared with saccular aneurysms.

Combination of rare right arterial variation with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. A case report.

A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed.

ADC mapping of chronic cerebral hypoperfusion induced by carotid artery stenosis.

BACKGROUND: Carotid artery stenosis is associated with the occurrence of acute and chronic ischemic lesions that increase with age in the elderly population. Diffusion Imaging and ADC mapping may be an appropriate method to investigate patients with chronic hypoperfusion consecutive to carotid stenosis. This non-invasive technique allows to investigate brain integrity and structure, in particular hypoperfusion induced by carotid stenosis diseases. The aim of this study was to evaluate the impact of a carotid stenosis on the parenchyma using ADC mapping. METHODS: Fifty-nine patients with symptomatic (33) and asymptomatic (26) carotid stenosis were recruited from our multidisciplinary consultation. Both groups demonstrated a similar degree of stenosis. All patients underwent MRI of the brain including diffusion-weighted MR imaging with ADC mapping. Regions of interest were defined in the anterior and posterior paraventricular regions both ipsilateral and contralateral to the stenosis (anterior circulation). The same analysis was performed for the thalamic and occipital regions (posterior circulation). RESULTS: ADC values of the affected vascular territory were significantly higher on the side of the stenosis in the periventricular anterior (P<0.001) and posterior (P<0.01) area. There was no difference between ipsilateral and contralateral ADC values in the thalamic and occipital regions. CONCLUSIONS: We have shown that carotid stenosis is associated with significantly higher ADC values in the anterior circulation, probably reflecting an impact of chronic hypoperfusion on the brain parenchyma in symptomatic and asymptomatic patients. This is consistent with previous data in the literature.

Intracranial stents being modeled as a porous medium: flow simulation in stented cerebral aneurysms.

Intracranial aneurysms may be treated by flow diverters, alternatively to stents and coils combination. Numerical simulation allows the assessment of the complex nature of aneurismal flow. Endovascular devices present a rather dense and fine strut network, increasing the complexity of the meshing. We propose an alternative strategy, which is based on the modeling of the device as a porous medium. Two patient-specific aneurysm data sets were reconstructed using conventional clinical setups. The aneurysms selection was done so that intra-aneurismal flow was shear driven in one and inertia driven in the other. Stents and their porous medium analog were positioned at the aneurysm neck. Physiological flow and standard boundary conditions were applied. The comparison between both approaches was done by analyzing the velocity, vorticity, and shear rate magnitudes inside the aneurysm as well as the wall shear stress (WSS) at the aneurysm surface. Simulations without device were also computed. The average flow reduction reaches 76 and 41% for the shear and inertia driven flow models, respectively. When comparing the two approaches, results show a remarkable similarity in the flow patterns and magnitude. WSS, iso-velocity surfaces and velocity on a trans-sectional plane are in fairly good agreement. The root mean squared error on the investigated parameters reaches 20% for aneurysm velocity, 30.6% for aneurysm shear rate, and 47.4% for aneurysm vorticity. It reaches 20.6% for WSS computed on the aneurysm surface. The advantages of this approach reside in its facility to implement and in the gain in computational time. Results predicted by the porous medium approach compare well with the real stent geometry model and allow predicting the main effects of the device on intra-aneurismal flow, facilitating thus the analysis.

Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment.

BACKGROUND AND PURPOSE: FD technology enables reconstructive repair of otherwise difficult-to-treat intracranial aneurysms. These stentlike devices may induce progressive aneurysm thrombosis without additional implants and may initiate complete reverse vessel remodeling. The associated vascular biologic processes are as yet only partially understood. MATERIALS AND METHODS: From 12 different centers, 13 cases of delayed postprocedural aneurysm rupture were recorded and analyzed. Symptom, aneurysm location and morphology, and the time elapsed from treatment until rupture were analyzed. RESULTS: There were 10 internal carotid and 3 basilar artery aneurysms. Mean aneurysm diameter was 22 ± 6 mm. Eleven patients were symptomatic before treatment. A single FD was used for all saccular aneurysms, while fusiform lesions were treated by using multiple devices. A supplementary loose coiling of the aneurysm was performed in 1 patient only. Ten patients developed early aneurysm rupture after FD treatment (mean, 16 days; range, 2-48 days); in 3 patients, rupture occurred 3-5 months after treatment. In all cases, most of the aneurysm cavity was thrombosed before rupture. The biologic mechanisms predisposing to rupture under these conditions are reviewed and discussed CONCLUSIONS: FDs alone may modify hemodynamics in ways that induce extensive aneurysm thrombosis. Under specific conditions, however, instead of reverse remodeling and cicatrization, aggressive thrombus-associated autolysis of the aneurysm wall may result in delayed rupture.

Penumbra system: a novel mechanical thrombectomy device for large-vessel occlusions in acute stroke.

BACKGROUND AND PURPOSE: Large IC artery occlusion is often resistant to recanalization. We present our initial experience with the PS. MATERIALS AND METHODS: Presenting with a severe acute ischemic stroke, the first 27 consecutive patients were considered for thromboaspiration therapy and retrospective data base analysis. All patients received standard thrombectomy treatment as monotherapy or in combination with thrombolysis or IC stent placement. The primary end point was revascularization of the target vessel to grade 2 or 3 on the TICI scale. Secondary end points were improvement of >4 points on the NIHSS score at discharge and favorable outcome, and improvement in overall mortality at 3 months and in sICH- and procedure-related adverse events. RESULTS: At baseline, the mean age was 66 +/- 14 years and the mean NIHSS score was 14 +/- 7. The anterior circulation was affected in 23 patients, and there were 4 basilar artery occlusions. Intracranial stent placement was performed in 4 patients. A recanalization to TICI 2 or 3 was achieved in 25 patients (93%). None of the patients developed sICH. At hospital discharge, 15 patients (56%) had an NIHSS improvement of >4 and 13 patients (48%) had an mRS score of <2 at 3 months. There was a significant correlation between complete vessel recanalization and favorable outcome. The all-cause mortality at 3 months was 11%. CONCLUSIONS: The PS showed a high potential for recanalization of acute thromboembolic occlusions of the large cerebral arteries. Complete recanalization was strongly correlated with good clinical outcome.

Methodologies to assess blood flow in cerebral aneurysms: current state of research and perspectives.

With intracranial aneurysms disease bringing a weakened arterial wall segment to initiate, grow and potentially rupture an aneurysm, current understanding of vessel wall biology perceives the disease to follow the path of a dynamic evolution and increasingly recognizes blood flow as being one of the main stakeholders driving the process. Although currently mostly morphological information is used to decide on whether or not to treat a yet unruptured aneurysm, among other factors, knowledge of blood flow parameters may provide an advanced understanding of the mechanisms leading to further aneurismal growth and potential rupture. Flow patterns, velocities, pressure and their derived quantifications, such as shear and vorticity, are today accessible by direct measurements or can be calculated through computation. This paper reviews and puts into perspective current experimental methodologies and numerical approaches available for such purposes. In our view, the combination of current medical imaging standards, numerical simulation methods and endovascular treatment methods allow for thinking that flow conditions govern more than any other factor fate and treatment in cerebral aneurysms. Approaching aneurysms from this perspective improves understanding, and while requiring a personalized aneurysm management by flow assessment and flow correction, if indicated.

Arterial spin labeling shows cortical collateral flow in the endovascular treatment of vasospasm after post-traumatic subarachnoid hemorrhage.

We report here on the case of a patient who, 10 days prior to his admission to hospital, had suffered a bicycle accident. He presented with signs of minor dysphasia. A brain CT-scan revealed slight subarachnoid hemorrhage (SAH) in the left sylvian fissure as well as narrowing of the distal M1 segment of the left middle cerebral artery (MCA) on CT-angiography. MRI showed diffusion abnormalities and hypoperfusion in the left MCA territory with cortical hyperperfusion on arterial spin labeling (ASL). Arteriography confirmed the vasospasm, but showed no sign of aneurysm. Angioplasty of the narrowed MCA was successful, and follow-up MRI showed reperfusion of the MCA territory.

Evaluation of perfusion CT and TIBI grade in acute stroke for predicting thrombolysis benefit and clinical outcome.

OBJECTIVE: To evaluate the prognostic accuracy of combining perfusion CT (PCT) and thrombolysis in brain ischemia (TIBI) ultrasonographic grade in the triage of stroke patients who will benefit from thrombolysis and in predicting the clinical outcome. METHODS: We conducted a prospective study of all consecutive stroke patients admitted to our hospital from March 2003 to July 2007, presenting with signs of acute stroke within the therapeutic window, who had undergone either intravenous or combined intravenous and intra-arterial thrombolysis. All patients were evaluated by a complete stroke CT protocol, transcranial color-coded duplex sonographic monitoring, follow-up imaging (CT or MRI) and clinical outcome at 3 months, as assessed by the modified Rankin scale (mRS). RESULTS: A total of 34 patients were included with a mean NIHSS on admission of 14.2. This study revealed that PCT had 95% sensitivity and 71% specificity in the evaluation of therapy benefit as well as 75% sensitivity and 39% specificity in predicting clinical outcome. The extent of ischemic tissue according to PCT and TIBI grade were significantly correlated (p<0.05). Using the MTT-TTP approach was an alternative to the classical MTT-CBV approach for determining tissue at risk. The clinical outcome assessed by the mRS was considered favorable (mRS 0-2) in 16 patients and unfavorable (mRS>2) in 18 patients. CONCLUSION: PCT was the most accurate predictor of both thrombolytic therapy benefit and clinical outcome. The TIBI score was useful for determining whether or not to perform intravenous therapy alone or as a combined therapy.

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

Light transport in tissue by 3D Monte Carlo: influence of boundary voxelization.

Monte Carlo (MC) based simulations of photon transport in living tissues have become the "gold standard" technique in biomedical optics. Three-dimensional (3D) voxel-based images are the natural way to represent human (and animal) tissues. It is generally believed that the combination of 3D images and MC based algorithms allows one to produce the most realistic models of photon propagation. In the present work, it is shown that this approach may lead to large errors in the MC data due to the "roughness" of the geometrical boundaries generated by the presence of the voxels. In particular, the computed intensity of the light detected on the tissue surface of a simple cubic tissue phantom may display errors from -80% to 120%. It is also shown that these errors depend in a complex manner on optical and geometrical parameters such as the interoptode distance, scattering coefficient, refractive index, etc. and on the degree of voxelization ("roughness") of the boundaries. It is concluded that if one wants to perform reliable 3D Monte Carlo simulations on complex geometries, such as human brain, skin or trabecular bone, it is necessary to introduce boundary meshing techniques or other equivalent procedures in the MC code to eliminate the deleterious effect of voxelization.

Effect of elastin degradation on carotid wall mechanics as assessed by a constituent-based biomechanical model.

Arteries display a nonlinear anisotropic behavior dictated by the elastic properties and structural arrangement of its main constituents, elastin, collagen, and vascular smooth muscle. Elastin provides for structural integrity and for the compliance of the vessel at low pressure, whereas collagen gives the tensile resistance required at high pressures. Based on the model of Zulliger et al. (Zulliger MA, Rachev A, Stergiopulos N. Am J Physiol Heart Circ Physiol 287: H1335-H1343, 2004), which considers the contributions of elastin, collagen, and vascular smooth muscle cells (VSM) in an explicit form, we assessed the effects of enzymatic degradation of elastin on biomechanical properties of rabbit carotids. Pressure-diameter curves were obtained for controls and after elastin degradation, from which elastic and structural properties were derived. Data were fitted into the model of Zulliger et al. to assess elastic constants of elastin and collagen as well as the characteristics of the collagen engagement profile. The arterial segments were also prepared for histology to visualize and quantify elastin and collagen. Elastase treatment leads to a diameter enlargement, suggesting the existence of significant compressive prestresses within the wall. The elastic modulus was more ductile in treated arteries at low circumferential stretches and significantly greater at elevated circumferential stretches. Abrupt collagen fiber recruitment in elastase-treated arteries leads to a much stiffer vessel at high extensions. This change in collagen engagement properties results from structural alterations provoked by the degradation of elastin, suggesting a clear interaction between elastin and collagen, often neglected in previous constituent-based models of the arterial wall.

Comment on 'the use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics'.

In this letter the authors highlight the presence of an error appearing in the discussion of the note 'The use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics' previously published by them (Binzoni et al 2006 Phys. Med. Biol. 51 N313). In the light of this error, the discussion and conclusions in the original paper are revised in this letter and the role of the use of the phase functions in MC simulations, interpreted in probabilistic terms, is better clarified. The exact definition for the probability density function for the deflection angle, in the case of the Henyey-Greenstein model, is also given.

Embolization of experimental wide-necked aneurysms with iodine-containing polyvinyl alcohol solubilized in a low-angiotoxicity solvent.

BACKGROUND AND PURPOSE: To evaluate the ready-to-use iodine-containing polyvinyl alcohol (I-PVA) dissolved in the low angiotoxic solvent N-methyl pyrrolidone (NMP) for embolization of porcine wide-necked aneurysms. METHODS: Fourteen broad-based carotid sidewall aneurysms were surgically constructed in 7 swine. I-PVA (40%) in NMP was injected under temporary balloon occlusion bridging the aneurysm neck. After 4 weeks, follow-up angiography, multisection CT angiography (MSCTA), and 3T MR imaging including MR angiography (MRA) sequences were performed. Afterward, harvested aneurysms were investigated histopathologically. RESULTS: The liquid embolic was well visible under fluoroscopy and displayed a favorable precipitation pattern, allowing for controlled polymer delivery. Ten aneurysms (71%) were initially completely occluded, whereas in 1 aneurysm, a minimal polymer leakage was observed. The other 4 aneurysms (29%) were almost completely occluded. One animal suffered a lethal rebleeding from the anastomosis after uneventful embolization. Aneurysms embolized with I-PVA could be discriminated well from the parent artery without beam-hardening artifacts on MSCTA, and no susceptibility artifacts were encountered on MR imaging. Histologic examination revealed all aneurysms covered with a membrane of fibroblasts and an endothelial cell layer while a moderate intraaneurysmal inflammatory response to the polymer was observed. CONCLUSION: I-PVA dissolved in NMP has proved its effectiveness for the embolization of experimental wide-necked aneurysms. This precipitating liquid embolic offers several interesting features in that it needs no preparation before use and no radiopaque admixtures, the latter allowing for artifact-free evaluation of treated aneurysms with MSCTA and MRA. Moreover, it uses NMP as a solvent, which has only a low angiotoxicity.

Organic solvents as vehicles for precipitating liquid embolics: a comparative angiotoxicity study with superselective injections of swine rete mirabile.

BACKGROUND AND PURPOSE: The organic solvent dimethyl-sulfoxide (DMSO), as a commonly used vehicle for nonadhesive liquid embolics, is not devoid of local angiotoxic effects. We compared microvascular toxicities of superselective infusions of DMSO with potentially more compatible solvents in swine rete mirabile. METHODS: Fourteen swine underwent angiography for superselective catheterization of 28 arteries of the rete while electrocardiography and intra-arterial pressure were continuously monitored. The investigated solvents were DMSO, dimethyl isosorbide (DMI), ethyl lactate, glycofurol 75, N-methyl pyrrolidone (NMP), and solketal. Control infusion of saline ruled out catheter induced vasospasm in all cases. Each artery of the rete was infused only once with 0.8 mL of one of the solvents over 60 seconds. Acute angiographic and hemodynamic consequences were evaluated. Blood samples were assessed for signs of intravascular hemolysis. Brains and retia were harvested for gross and histopathologic investigation. RESULTS: On the basis of the angiographic data, DMSO induced the most pronounced vasospasm with the longest recovery period of all solvents investigated. Ethyl lactate, glycofurol 75, and solketal elicited less severe vasospasms and accordingly resolved much more quickly. DMI and NMP induced only minimal vasospasms with comparably short duration. No solvent caused significant hemodynamic alterations or hemolysis. Gross inspection of brains showed no abnormalities, whereas histopathologic examination revealed mostly nonspecific findings. One rete exposed to solketal displayed possible causal histotoxic changes. CONCLUSION: DMI and NMP produced far less vasospasm than DMSO. No changes in hemodynamic or hemolytic parameters and no histopathologic findings were observed with infusion of these solvents.

Volume changes of experimental carotid sidewall aneurysms due to embolization with liquid embolic agents: a multidetector CT angiography study.

Iodine-containing polyvinyl alcohol polymer (I-PVAL) is a novel precipitating liquid embolic that allows for artifact-free evaluation of CT angiography (CTA). As accurate aneurysm volumetry can be performed with multidetector CTA, we determined volumes of experimental aneurysms before, immediately after, and 4 weeks after embolization of 14 porcine experimental carotid sidewall aneurysms with this liquid embolic. An automated three-dimensional software measurement tool was used for volumetric analysis of volume-rendering CTA data. Furthermore, intra-aneurysmal pressure changes during liquid embolization were measured in four silicone aneurysms and potential polymer volume changes within 4 weeks were assessed in vitro. Liquid embolic injection was performed during temporary balloon occlusion of the aneurysm neck, resulting in a mean occlusion rate of 98.3%. Aneurysms enlarged significantly during embolization by 61.1 +/- 28.9%, whereas a significant shrinkage of 5.6 +/- 2.7% was observed within the follow-up period. Histologic analysis revealed an inflammatory foreign body reaction with partial polymer degradation. In silicone aneurysm models, intra-aneurysmal pressure remained unchanged during liquid embolic injection, whereas balloon inflation resulted in a mean pressure increase of 31.2 +/- 0.7%. No polymer shrinkage was observed in vitro. The aneurysm enlargement noted was presumably due to pressure elevation after balloon inflation, which resulted in dilatation of the weak venous wall of the newly constructed aneurysm--another shortcoming of this experimental aneurysm model. The volume decrease after 4 weeks expressed partial polymer degradation.