Intra-aneurysmal Thrombus Formation Research Articles

High signal intensity of the intraaneurysmal sac on T1 CUBE imaging as a predictor of aneurysm stability after coil embolization.

Histopathological studies of aneurysms after coil embolization showed that thrombus formation during the first month after endovascular treatment (EVT) played an important role in the healing process. The authors hypothesized that dedicated T1-weighted imaging may be used to predict stable aneurysms by visualizing the thrombus status within coil-treated aneurysms. Therefore, this study investigated the relationship between the signal intensity (SI) of the intraaneurysmal sac after coil embolization and aneurysm stability. The study population included 82 patients with 86 aneurysms who underwent T1-weighted 3D black-blood fast spin-echo (T1 CUBE) imaging within 1 month after coil embolization between 2019 and 2022. The relative SI of a coil-treated aneurysm (RSIcoiled) was calculated as follows: the mean SI of the intraaneurysmal sac/the mean SI of the genu of the corpus callosum. Aneurysms with enlarged remnants on MR angiography (MRA) within 6 months after EVT were defined as recurrence, while a decrease of intraaneurysmal flow on MRA was defined as improved embolization status. Stable aneurysms were defined as improvement or no change in embolization status 6 months after coil embolization. The volume embolization ratio (VER) was calculated as the ratio of the packed coil volume to the aneurysm volume. Differences between stable and recurrent aneurysms were examined. All aneurysms were divided into high and low RSIcoiled groups based on the cutoff value of RSIcoiled, and differences between the two groups were also evaluated. Recurrence was confirmed for 26 of 86 aneurysms. A univariable analysis showed that small aneurysms, high VER, and high RSIcoiled were associated with aneurysm stability. In the receiver operating characteristic curve analysis, the optimal cutoff value for RSIcoiled to differentiate stable from recurrent aneurysms was 0.54. The cutoff value for RSIcoiled was selected as 0.50 (sensitivity 0.77, specificity 0.70) because it was half the value of the SI of the corpus callosum and close to the optimal cutoff value. In a multivariable analysis, RSIcoiled > 0.50 (OR 8.1, 95% CI 2.5-27) remained a significant factor for aneurysm stability. The high RSIcoiled group showed a higher rate of an improved embolization status (26% vs 6.1%, p = 0.022) and stable aneurysms (85% vs 15%, p = 0.0002). RSIcoiled was associated with postcoiling aneurysm stability. High RSIcoiled might imply intraaneurysmal thrombus formation associated with the healing process of coil-treated aneurysms.

Outcomes following aneurysmal coil embolization with intentionally shortened low-profile visible intraluminal support stent deployment.

Among all stents available for neuroendovascular therapy, the low-profile visible intraluminal support stent bears the highest metal coverage ratio. We deployed a low-profile visible intraluminal support stent with a delivery wire or/and microcatheter system push action to shorten the low-profile visible intraluminal support stent and thus achieve a flow diversion effect. We report our single-institution experience with the use of low-profile visible intraluminal support stents for intentionally shortened deployment (shortening group) and non-shortened deployment (non-shortening group) for unruptured intracranial aneurysms. We retrospectively reviewed the medical records of 130 patients with 131 intracranial aneurysms who were treated with low-profile visible intraluminal support stent-assisted coil embolization from February 2016-January 2019. All perioperative complications were noted. Every 6 months, we re-examined the patients with cerebral angiography or magnetic resonance angiography. The outcomes of aneurysm occlusion were evaluated by the modified Raymond-Roy occlusion classification. We used the finite element method and computational fluid dynamics to investigate the hemodynamics after shortened low-profile visible intraluminal support stent deployment. Immediately after treatment, the modified Raymond-Roy occlusion classification was significantly better in the shortening group than in the non-shortening group (p<0.05). The latest angiographic outcomes showed the same tendency. Hemodynamic analysis by computational fluid dynamics suggested an adequate flow diversion effect with the use of our intentional shortening method. Stent-assisted coil embolization using this technique showed good results of a high complete occlusion rate and low complication rate. These findings suggest that shortened low-profile visible intraluminal support stent deployment yields a flow diversion effect and may lead to early intra-aneurysmal thrombus formation.

Healing of Aneurysm after Treatment Using Flow Diverter Stent : Histopathological Study in Experimental Canine Carotid Side Wall Aneurysm

ObjectiveDespite widespread use of flow diverters (FDs) to treat aneurysms, the exact healing mechanism associated with FDs remains poorly understood. We aim to describe the healing process of aneurysms treated using FDs by demonstrating the histopathologic progression in a canine aneurysm model. MethodsTwenty-one side wall aneurysms were created in common carotid artery of eight dogs and treated with two different FDs. Angiographic follow-ups were done immediately after placement of the device, 4 weeks and 12 weeks. At last follow-up, the aneurysm and the device-implanted parent artery were harvested. ResultsHistopathologic findings of aneurysms at 4 weeks follow-up showed intra-aneurysm thrombus formation in laminating fashion, and neointimal thickening at the mid-segment of aneurysm. However, there are inhomogenous findings in aneurysms treated with the same type of FD showing same angiographic outcomes. At 12 weeks, aneurysms of complete and near-complete occlusion revealed markedly shrunken aneurysm filled with organized connective tissues with thin neointima. Aneurysms of incomplete occlusion at 12 weeks showed small amount of organized thrombus around fringe neck and large empty space with thick neointmal formation. Neointimal thickness and diameter stenosis was not significantly different between the groups of FD specification and follow-up period. ConclusionIntra-aneurysmal thrombus formation and organization seem to be an important factor for the complete occlusion of aneurysms treated using the FD. Neointimal formation could occur along the struts of the FD independently of intra-aneurysmal thrombus formation. However, neointimal formation could not solely lead to complete aneurysm healing.

Antiphospholipid antibodies predict progression of abdominal aortic aneurysms.

Antiphospholipid antibodies (aPLs) frequently occur in autoimmune and cardiovascular diseases and correlate with a worse clinical outcome. In the present study, we evaluated the association between antiphospholipid antibodies (aPLs), markers of inflammation, disease progression and the presence of an intra-aneurysmal thrombus in abdominal aortic aneurysm (AAA) patients.APLs ELISAs were performed in frozen serum samples of 96 consecutive AAA patients and 48 healthy controls yielding positive test results in 13 patients (13.5%) and 3 controls (6.3%; n.s.). Nine of the 13 aPL-positive AAA patients underwent a second antibody testing >12 weeks apart revealing a positive result in 6 cases. APL-positive patients had increased levels of inflammatory markers compared to aPL-negative patients. Disease progression was defined as an increase of the AAA diameter >0.5 cm/year measured by sonography. Follow-up was performed in 69 patients identifying 41 (59.4%) patients with progressive disease. Performing multipredictor logistic regression analysis adjusting for classical AAA risk factors as confounders, the presence of aPLs at baseline revealed an odds ratio of 9.4 (95% CI 1.0–86.8, p = 0.049) to predict AAA progression. Fifty-five patients underwent a computed tomography in addition to ultrasound assessment indicating intra-aneurysmal thrombus formation in 82.3%. Median thrombus volume was 46.7 cm3 (1.9–377.5). AAA diameter correlated with the size of the intra-aneurysmal thrombus (corrcoeff = 0.721, p<0.001), however neither the presence nor the size of the intra-aneurysmal thrombus were related to the presence of aPLs.In conclusion, the presence of aPLs is associated with elevated levels of inflammatory markers and is an independent predictor of progressive disease in AAA patients.

Y-configuration double-stent-assisted coiling using two closed-cell stents for wide-neck basilar tip aneurysms.

This study aimed to evaluate clinical and angiographic outcomes of Y-configuration double-stent-assisted (Y-stent) coiling using two closed-cell stents for wide-necked basilar tip aneurysm (BTA). A total of 25 patients underwent Y-stent coiling using two closed-cell stents as a first-time treatment in 18 (3 ruptured) BTAs, retreatment in 2 BTAs and as a third treatment in 5 wide-necked BTAs. Clinical and angiographic outcomes were evaluated retrospectively. Treatment-related complications were three (12.0 %) thromboembolic infarctions due to two acute in-stent thromboses and one embolism. Twenty-two (88 %) patients had favorable outcomes (modified Rankin scale score [mRS], 0-2) during the follow-up period (mean, 30 months; range, 6-54 months). Two patients died: one from initial subarachnoid hemorrhage and the other from intracerebral hemorrhage due to underlying Moyamoya disease. Post-treatment angiograms showed complete occlusion in nine aneurysms, residual neck in 11 aneurysms and residual sac in five aneurysms. Follow-up angiograms were available at least once between 5 to 34 months (mean, 16 months) in 21 patients. Nineteen patients showed improved or stable states (complete occlusion, n = 17; residual neck, n = 2). Major recurrences occurred in two BTAs (9.5 %). Those two major recurrent aneurysms had been large-sized aneurysms at the initial coiling procedure. Both showed not only coil compaction but also progressive growth to giant-sized aneurysms and intra-aneurysmal thrombus formation at the Y-stent coiling as a third-time treatment. Y-stent coiling using two closed-cell stents is a safe and durable treatment option for wide-necked BTA, but may have limited efficacy for large/giant sized and thrombosed aneurysms.

Correlation of thrombus formation on 7 T MRI with histology in a rat carotid artery side wall aneurysm model

Background/purposeVarious aneurysm animal models have been utilized to study the histological reaction post coil embolization. Our aim was to evaluate the imaging findings at day 14 of a rat external...

Intra-Aneurysmal Pressure and Flow Changes Induced by Flow Diverters: Relation to Aneurysm Size and Shape

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. 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. 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. 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.

Early Ceasing of Intra-aneurysmal Contrast Opacification During Coil Embolization in Ruptured Aneurysms Compared With Unruptured Aneurysms

The difference between coil-embolized ruptured and unruptured aneurysms with respect to intra-aneurysmal thrombus formation remains to be determined. We examined whether there was a difference between ruptured and unruptured coil-embolized aneurysms in the rate and timing of thrombus formation in the aneurysmal sac and discuss the effect of thrombus on the treatment outcome. We evaluated 209 aneurysms with an aneurysmal dome smaller than 10 mm and a neck size less than 4 mm. Of these, 91 (43.5%) were ruptured. We assessed intra-aneurysmal thrombus formation by the coil-packing ratio (CPR): the percentage of coil volume occupying the aneurysmal sac. The initial CPR was defined as the CPR at which contrast influx into the sac ceased and the final CPR as that at the end of the procedure. ΔCPR was calculated as the difference between initial and final CPRs. Embolized aneurysms were evaluated on follow-up angiograms. The initial CPR was significantly lower in ruptured aneurysms (P < .01), and there was not a significant difference in the final CPR between ruptured and unruptured aneurysms (P = .05). ΔCPR was significantly higher in ruptured aneurysms (P < .01). The rate of aneurysmal recanalization was significantly higher in ruptured aneurysms (P < .05). The incidence of recanalization was high in ruptured aneurysms with low initial CPR and ΔCPR values. In ruptured aneurysms, intra-aneurysmal thrombus formation tends to occur in the earlier stages of coil embolization. In some cases, thrombus formation may inhibit dense coil packing and result in recanalization.

Computational fluid dynamics

Computational fluid dynamics

Hemodynamics altered by placing helix stents in an aneurysm at a 45° angle to the curved vessel

Flow visualization, particle image velocimetry and numerical computation have been complementarily performed to study the fluid flow inside a stented lateral aneurysm. The curved afferent vessel had an inner diameter of 5 mm. The diameters of the aneurysmal orifice, neck and fundus were 7 mm, 5 mm and 7.5 mm, respectively, and the distance between the orifice and dome measured 10 mm. Stents with various porosities were examined. A volume-flow rate waveform of the internal carotid artery was reconstructed with a Wormersley number of 4 and Reynolds number ranging from 202 to 384 in a cardiac cycle. Results are presented in terms of the main and secondary flow velocity vector fields, the inflow rates into the aneurysm and the intra-aneurysmal wall shear stress and pressure. Some comparisons of the computed results with the experimental results and the data available from the literature are also made. It is found that the placement of stents for endovascular treatment is more critical for an unstented parent vessel with curvature than without since the maximum inflow rate of the former is 15 times the latter. The critical porosity of 70% below which an inhibition of intra-aneurysmal thrombus formation will not occur is identified for the first time.

In vitro and in vivo Studies of the Extent of Electrothrombotic Deposition of Blood Elements on the Surface of Electrolytically Detachable Coils.

Endovascular treatment of intracranial aneurysms with electrolytically detachable coils is often claimed to be based on electrothrombosis, i.e. intra-aneurysmal thrombus formation through applied direct current. Despite the fact that this concept was described more than a century ago, the significance of electrothrombosis in the endovascular treatment of aneurysms remains debatable. Apart from electrothrombosis, mechanical obliteration of the aneurysmal lumen might be one of the many possible mechanisms to explain why and how detachable coils are effective in preventing aneurysms from (re-)rupture. The purpose of this experimental study was to investigate to what extent direct current comparable to that used for coil detachment would influence the adhesion of cellular and liquid blood components to the surface of electrolytically detachable platinum coils. For the in vitro study, electrolytically detachable platinum coils of various types were exposed to stagnant heparinised blood for a total of 16 h, without or with applied direct current for 30 or 90 s (1 mA, 4-6 V, coil as anode). For the in vivo study, electrolytically detachable platinum coils were exposed to flowing blood for 180 s, without or with applied direct current (2 mA, 4-6 V, coil as either anode or cathode), without anti-coagulation and after intravenous administration of 5000 U Heparin and again after the intravenous administration of 500 mg Aspisol in addition to Heparin. After exposure to blood according to these different experimental protocols, the coils were fixed in formalin solution, gold coated and examined by scanning electron microscopy. Thrombus formation on the surface of all unfibred coils was thin and highly variable both from coil to coil, and on different areas of any given coil. The application of direct current minimally enhanced thrombus formation in stagnant blood in vitro, but not in vivo. The cellular and fibrin adhesions on the coil surfaces without and with applied current did not effectively increase the diameter or volume of unfibred coils. Coils with attached nylon fibres, however, proved to be highly thrombogenic without or with application of current. In fibred coils, surface adhesions without and with applied current were voluminous enough to effectively increase the diameter of the coil, potentially important for the process of endosaccular aneurysm occlusion. Electrothrombosis plays no role in the endovascular treatment of intracranial aneurysms with electrolytically detachable coils. This explains why platinum coils with non-electrolytic detachment mechanisms show a similar efficiency and recurrence rate.

Histopathological Findings in Experimental Aneurysms Embolized with Conventional and Thrombogenic/Antithrombolytic Guglielmi Coils

We studied the short- and long-term histological responses induced by conventional and modified electronically detachable coils (GDCs) in experimental aneurysms. Eighteen carotid bifurcation aneurysms were produced microsurgically in rabbits. Six animals each were treated either with conventional or with GDCs coated with a mixture of tissue-thromboplastin to enhance intra-aneurysmal thrombus formation and of plasminogen activator inhibitor type-1 (PAI-1) in inhibit intra-aneurysmal clot fibrinolysis. Six served as untreated controls. Follow-up angiograms were obtained immediately and at 3, 6, 9, 12, 17, and 24 weeks after embolization prior to sacrifice of the animals. All aneurysms were studied macroscopically and histopathologically with the coils in situ. Five of six control aneurysms remained patent. Endovascular occlusion rates between > 90% and 100% were achieved in nine of twelve coiled aneurysms. Follow-up angiography demonstrated recanalization and coil compaction in 5 of them. Gross and microscopic histopathological examination revealed a membrane covering the orifice, intra-aneurysmal scar formation, and development of a neo-intima in both treatment groups at 17 and 24 weeks postembolization. The granulation tissue response appeared to be equally distributed in aneurysms treated with either uncoated or coated coils. Further quantitative morphometric studies are needed to prove if a thrombogenic/antithrombolytic coil-coating might be of value in providing a more enduring anatomic result after GDC-treatment of human brain aneurysms.

大動脈りゅう内血栓形成の予測 Ｉｎ‐１１１血小板シンチグラフィー，ＦＰＡ，ＦＤＰ‐Ｅを中心に

We evaluated the examinations to predict intra-aneurysmal thrombus-formation by the estimation of FPA and FDP-E in blood, and scintigraphy by In-111-loaded platelets (platelets scintigraphy) in 11 patients.The FDP-E value was 682.7±761.97ng/ml (Mean±SD), and seems to reflect the quantity of intra-aneurysmal thrombus. Especially, all 4 cases with FDP-E higher than 500ng/ml had massive intra-aneurysmal thrombus by CT scan.The FPA valuue was 33.0±63.25ng/ml (Mean±SD), and seemed to indicate thrombogenicity. All 5 cases with FPA values higher than 5.0ng/ml showed strong radioactivity at the same site of intra-aneurysmal thrombus shown by platelets scientigraphy.Both acute dissecting aneurysm cases showed high FPA values (238ng/ml and 5.9ng/ml), while all 3 chronic cases showed normal FPA values (less than 2.0ng/ml).In the case of acute dissecting aneurysm with FPA value of 23.8ng/ml, platele scintigraphy showed strong radioactivity in the false luemn. Moreover, the false lumen was occluded by thrombus after 6 months later, and FPA decreased to 0.6ng/ml. This case shows that platlet scintigraphy is valuable for the diangosis of the site of active thrombus in aortic aneurysm.These results suggests that it is possible to predict intra-aneurysmal thrombus formation by measuring FPA and FDP-E and In-111 loaded platelet scintigraphy.

Experimental production of aneurysm by vein-pouch graft and observation of intra-aneurysmal hemodynamics

Utilizing the external jugular vein graft, veinpouch aneurysm of 6 to 9mm in orifice and of 5 to 8mm in height was made on the common carotid artery of the dog. Longitudinal incision of 8 to 12mm in length was made in the artery instead of “V” incision used by German and Black. The open end of the vein-pouch graft was cut obliquely and sutured to the arterial incision to make an angle of 65 to 70° between the aneurysm and the artery.Intraaneurysmal hemodynamics was observed through thin wall of the aneurysm with highspeed 16mm movie. Jet flow was seen at the dome of the aneurysm, corresponding to each systole. Turbulence was most remarkable on the distal side of the aneurysmal sack. These flows were markedly reduced by mechanical stenosis of the parent artery on the cardiac side, which decreased arterial flow to 50% of the resting value, and they were completely abolished by carotid occlusion. Following carotid occlusion, intraaneurysmal mean pressure was reduced to 71% of the original level on an average and pulse pressure was decreased to 0 to 5mmHg.Patency of these vein-pouch aneurysms was evaluated on angiogram. One week after the aneurysm had been made, approximately 80% of the aneurysms which had the larger orifice than their was completely patent. No intraaneurysmal thrombus formation nor stenosis of the parent artery was revealed by angiogram. All aneurysms which were completely patent at this point remained under the same state during the follow-up of 1 month.Histological examination cofirmed that the junction between the vein-pouch and the artery was covered smoothly with a layer of endothelium extending from the artery. No degenerative change of the aneurysmal wall nor thrombus formation was found.This vein-pouch aneurysm may be one of most desirable experimental models for study on intraaneurysmal hemodynamics and treatment of an intracranial aneurysm.