Safety and Efficacy of the FRED Jr Flow Re-Direction Endoluminal Device for Intracranial Aneurysms: Retrospective Multicenter Experience With Emphasis on Midterm Results

Background and Purpose: Flow diversion is increasingly used as an endovascular treatment for intracranial aneurysms. In this retrospective multicenter study, we analyzed the safety and efficacy of the treatment of intracranial, unruptured, or previously treated but recanalized aneurysms using Flow Re-Direction Endoluminal Device (FRED) Jr with emphasis on midterm results. Materials and Methods: Clinical and radiological records of 150 patients harboring 159 aneurysms treated with FRED Jr at six centers between October 2014 and February 2020 were reviewed and consecutively included. Clinical outcome was measured by using the modified Rankin Scale (mRS). Anatomical results were assessed according to the O’Kelly-Marotta (OKM) scale and the Cekirge-Saatci Classification (CSC) scale. Results: The overall complication rate was 24/159 (16%). Thrombotic-ischemic events occurred in 18/159 treatments (11%). These resulted in long-term neurological sequelae in two patients (1%) with worsening from pre-treatment mRS 0–2 and mRS 4 after treatment. Complete or near-complete occlusion of the treated aneurysm according to the OKM scale was reached in 54% (85/158) at 6-month, in 68% (90/133) at 1-year, and in 83% (77/93) at 2-year follow-up, respectively. The rates of narrowing or occlusion of a vessel branch originating from the treated aneurysm according to the CSC scale were 11% (12/108) at 6-month, 20% (17/87) at 1-year, and 23% (13/57) at 2-year follow-up, respectively, with all cases being asymptomatic. Conclusions: In this retrospective multicenter study, FRED Jr was safe and effective in the midterm occlusion of cerebral aneurysms. Most importantly, it was associated with a high rate of good clinical outcome

Specific CT 3D rendering of the treatment zone after Irreversible Electroporation (IRE) in a pig liver model: the “Chebyshev Center Concept” to define the maximum treatable tumor size

Background: Size and shape of the treatment zone after Irreversible electroporation (IRE) can be difficult to depict due to the use of multiple applicators with complex spatial configuration. Exact geometrical definition of the treatment zone, however, is mandatory for acute treatment control since incomplete tumor coverage results in limited oncological outcome. In this study, the “Chebyshev Center Concept” was introduced for CT 3d rendering to assess size and position of the maximum treatable tumor at a specific safety margin. Methods: In seven pig livers, three different IRE protocols were applied to create treatment zones of different size and shape: Protocol 1 (n = 5 IREs), Protocol 2 (n = 5 IREs), and Protocol 3 (n = 5 IREs). Contrast-enhanced CT was used to assess the treatment zones. Technique A consisted of a semi-automated software prototype for CT 3d rendering with the “Chebyshev Center Concept” implemented (the “Chebyshev Center” is the center of the largest inscribed sphere within the treatment zone) with automated definition of parameters for size, shape and position. Technique B consisted of standard CT 3d analysis with manual definition of the same parameters but position. Results: For Protocol 1 and 2, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were not significantly different between Technique A and B. For Protocol 3, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were significantly smaller for Technique A compared with Technique B (41.1 ± 13.1 mm versus 53.8 ± 1.1 mm and 39.0 ± 8.4 mm versus 53.8 ± 1.1 mm; p < 0.05 and p < 0.01). For Protocol 1, 2 and 3, sphericity of the treatment zone was significantly larger for Technique A compared with B. Conclusions: Regarding size and shape of the treatment zone after IRE, CT 3d rendering with the “Chebyshev Center Concept” implemented provides significantly different results compared with standard CT 3d analysis. Since the latter overestimates the size of the treatment zone, the “Chebyshev Center Concept” could be used for a more objective acute treatment control

Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. To prevent severe infection, mass COVID-19 vaccination campaigns with several vaccine types are currently underway. We report pathological and immunological findings in 8 patients who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19. We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (5 female, 3 male) with a median age of 41.5 years (range, 24 to 53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccination. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5 x109/L (range, 8 to 92). Three had a fatal outcome and 5 were successfully treated. Autopsies showed arterial and venous thromboses in various organs and the occlusion of glomerular capillaries by hyaline thrombi. Sera from VITT patients contain high titer antibodies against platelet factor 4 (PF4) (OD 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P-selectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT

Glue, Onyx, Squid or PHIL? Liquid Embolic Agents for the Embolization of Cerebral Arteriovenous Malformations and Dural Arteriovenous Fistulas

Background!#!Endovascular embolization is an effective treatment option for cerebral arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). A variety of liquid embolic agents have been and are currently used for embolization of AVMs and DAVFs. Knowledge of the special properties of the agent which is used is crucial for an effective and safe embolization procedure.!##!Material and methods!#!This article describes the properties and indications of the liquid embolic agents which are currently available: cyanoacrylates (also called glues), and the copolymers Onyx, Squid and PHIL, as well as their respective subtypes.!##!Results!#!Cyanoacrylates were the predominantly used agents in the 1980s and 1990s. They are currently still used in specific situations, for example for the occlusion of macro-shunts, for the pressure cooker technique or in cases in which microcatheters are used that are not compatible with dimethyl-sulfoxide. The first broadly used copolymer-based embolic agent Onyx benefits from a large amount of available experience and data, which demonstrated its safety and efficacy in the treatment of cerebral vascular malformations, while its drawbacks include temporary loss of visibility during longer injections and artifacts in cross-sectional imaging. The more recently introduced agents Squid and PHIL aim to overcome these shortcomings and to improve the success rate of endovascular embolization. Novelties of these newer agents with potential advantages include extra-low viscosity versions, more stable visibility, and a lower degree of imaging artifacts.!##!Conclusion!#!All the available liquid embolic agents feature specific potential advantages and disadvantages over each other. The choice of the most appropriate embolic agent must be made based on the specific material characteristics of the agent, related to the specific anatomical characteristics of the target pathology

The Local Intraarterial Administration of Nimodipine Might Positively Affect Clinical Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage and Delayed Cerebral Ischemia

The effect of the intraarterial administration of nimodipine as a rescue measure to treat delayed vasospasm after aSAH remains understudied; therefore, we evaluated its effect on short- and long-term functional and neuropsychological outcomes after aSAH. In this prospective observational study, a total of 107 consecutive patients treated for aSAH of WFNS grades I–V were recruited. At follow-up visits 3-, 12- and 24-months after the hemorrhage, functional outcome was assessed using the Extended Glasgow Outcome (GOSE) and modified Rankin (mRS) scales, while neurocognitive function was evaluated using the screening module of the Neuropsychological Assessment Battery (NAB-S). The outcome of patients, who had received rescue therapy according to the local standard treatment protocol (interventional group, n = 37), and those, who had been treated conservatively (conservative group, n = 70), were compared. Even though significantly more patients in the interventional treatment group suffered from high-grade aSAH (WFNS Grades IV and V, 54.1% vs. 31.4%, p = 0.04) and required continuous drainage of cerebrospinal fluid at discharge (67.7% vs. 37.7%, p = 0.02) compared to the control group, significant differences in functional outcome were present only at discharge and three months after the bleeding (GOSE > 4 in 8.1% vs. 41.4% and 28.6% vs. 72.7%, p < 0.001 and p = 0.01 for the interventional and control group, respectively). Thereafter, group differences were no longer significant. While significantly more patients in the intervention group had severe neuropsychological deficits (76.3% vs. 36.0% and 66.7% vs. 29.2%, p = 0.04 and 0.05, respectively) and were unable to work (5.9% vs. 38.1%, p = 0.03 at twelve months) at three and twelve months after the hemorrhage, no significant differences between the two groups could be detected at long-term follow-up. The presence of moderate neuropsychological impairments did not significantly differ between the groups at any timepoint. In conclusion, despite initially being significantly more impaired, patients treated with intraarterial administration of nimodipine reached the same functional and neuropsychological outcomes at medium- and long-term follow-up as conservatively treated patients suggesting a potential beneficial effect of intraarterial nimodipine treatment for delayed vasospasm after aSAH

Iterative Metal Artifact Reduction (iMAR) of the Non-adhesive Liquid Embolic Agent Onyx in Computed Tomography

Background!#!A drawback of Onyx, one of the most used embolic agents for endovascular embolization of intracranial arteriovenous malformations (AVM), is the generation of imaging artifacts (IA) in computed tomography (CT). Since these artifacts can represent an obstacle for the detection of periprocedural bleeding, this study investigated the effect of artifact reduction by an iterative metal artifact reduction (iMAR) software in CT in a brain phantom.!##!Methods!#!Two different in vitro models with two-dimensional tube and three-dimensional AVM-like configuration were filled with Onyx 18. The models were inserted into a brain imaging phantom and images with (n = 5) and without (n = 10) an experimental hemorrhage adjacent were acquired. Afterwards, the iMAR algorithm was applied for artifact reduction. The IAs of the original and the post-processed images were graded quantitatively and qualitatively. Moreover, qualitative definition of the experimental hemorrhage was investigated.!##!Results!#!Comparing the IAs of the original and the post-processed CT images, quantitative and qualitative analysis showed a lower degree of IAs in the post-processed images, i.e. quantitative analysis: 2D tube model: 23.92 ± 8.02 Hounsfield units (HU; no iMAR; mean ± standard deviation) vs. 5.93 ± 0.43 HU (with iMAR; p < 0.001); qualitative analysis: 3D AVM model: 4.93 ± 0.18 vs. 3.40 ± 0.48 (p < 0.001). Furthermore, definition of the experimental hemorrhage was better in the post-processed images of both in vitro models (2D tube model: p = 0.004; 3D AVM model: p = 0.002).!##!Conclusion!#!The iMAR algorithm can significantly reduce the IAs evoked by Onyx 18 in CT. Applying iMAR could thus improve the accuracy of postprocedural CT imaging after embolization with Onyx in clinical practice

Sine Spin flat detector CT can improve cerebral soft tissue imaging: a retrospective in vivo study

Abstract Background Flat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging within the angiography suite. Novel technical developments such as the Sine Spin FDCT (S-FDCT) may provide an improved cerebral soft tissue contrast. This study investigates the effect of S-FDCT on the differentiation between gray and white matter compared to conventional FDCT (C-FDCT) and multidetector computed tomography (MDCT). Methods A retrospective analysis of a prospectively maintained patient database was performed, including patients who underwent mechanical thrombectomy in our institution and received S-FDCT or C-FDCT as well as MDCT. Differentiation between gray and white matter on the contralateral hemisphere to the ischemic stroke was analyzed quantitatively by contrast-to-noise ratio (CNR) and qualitatively (5-point ordinal scale). Results In a cohort of 109 patients, MDCT demonstrated the best differentiation between gray and white matter compared to both FDCT techniques (p ≤ 0.001). Comparing both generations of FDCT, S-FDCT provided better visibility of the basal ganglia (p = 0.045) and the supratentorial cortex (p = 0.044) compared to C-FDCT both in quantitative and qualitative analyses. Median CNR were as follows: S-FDCT 2.41 (interquartile range [IQR] 1.66–3.21), C-FDCT 0.96 (0.46–1.70), MDCT 3.43 (2.83–4.17). For basal ganglia, median score and IQR were as follows: S-FDCT 2.00 (2.00–3.00), C-FDCT 1.50 (1.00–2.00), MDCT 5.00 (4.00–5.00). Conclusions The novel S-FDCT improves the periinterventional imaging quality of cerebral soft tissue compared to C-FDCT. Thus, it may improve the diagnosis of complications within the angiography suite. MDCT provides the best option for x-ray-based imaging of the brain tissue. Relevance statement Flat detector computed tomography is a promising technique for cerebral soft tissue imaging, while the novel Sine Spin flat detector computed tomography technique improves imaging quality compared to conventional flat detector computed tomography and thus may facilitate periinterventional diagnosis of gray and white matter. Key points • Flat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging. • The potential of novel Sine Spin FDCT (S-FDCT) is unknown so far. • S-FDCT improves the visibility of cerebral soft tissue compared to conventional FDCT. • Multidetector computed tomography is superior to both FDCT techniques. • S-FDCT may facilitate the evaluation of brain parenchyma within the angiography suite. Graphical Abstrac

Imaging Artifacts of Nonadhesive Liquid Embolic Agents in Conventional and Cone-beam CT in a Novel in Vitro AVM Model

Background!#!A major drawback of liquid embolic agents (LEAs) is the generation of imaging artifacts (IA), which may represent a crucial obstacle for the detection of periprocedural hemorrhage or subsequent radiosurgery of cerebral arteriovenous malformations (AVMs). This study aimed to compare the IAs of Onyx, Squid and PHIL in a novel three-dimensional in vitro AVM model in conventional computed tomography (CT) and cone-beam CT (CBCT).!##!Methods!#!Tubes with different diameters were configured in a container resembling an AVM with an artificial nidus at its center. Subsequently, the AVM models were filled with Onyx 18, Squid 18, PHIL 25% or saline and inserted into an imaging phantom (n = 10/LEA). Afterwards CT and CBCT scans were acquired. The degree of IAs was graded quantitatively (Hounsfield units in a defined region of interest) and qualitatively (feasibility of defining the nidus)-Onyx vs. Squid vs. PHIL vs. saline, respectively.!##!Results!#!Quantitative density evaluation demonstrated more artifacts for Onyx compared to Squid and PHIL, e.g. 48.15 ± 14.32 HU for Onyx vs. 7.56 ± 1.34 HU for PHIL in CT (p < 0.001) and 41.88 ± 7.22 density units (DU) for Squid vs. 35.22 ± 5.84 DU for PHIL in CBCT (p = 0.044). Qualitative analysis showed less artifacts for PHIL compared to Onyx and Squid in both imaging modalities while there was no difference between Onyx and Squid regarding the definition of the nidus (p > 0.999).!##!Conclusion!#!In this novel three-dimensional in vitro AVM model, IAs were higher for the EVOH/tantalum-based LEAs Onyx and Squid compared to iodine-based PHIL. Onyx induced the highest degree of IAs with only minor differences to Squid

Concomitant Acute Ischemic Stroke and Upper Extremity Arterial Occlusion: Feasibility of Mechanical Thrombectomy of the Upper Limb Using Neurointerventional Devices and Techniques

Background: Concomitant acute ischemic stroke (AIS) caused by large vessel occlusion (LVO), and acute upper extremity arterial occlusion causing upper limb ischemia (ULI) is a rarely observed coincidence. The first-line treatment for AIS is mechanical thrombectomy (MT), with or without additional intravenous thrombolysis, while there are different pharmacological, surgical and endovascular treatment options for an acute occlusion of the UL arteries. Here, we describe the practicability, efficacy and safety of neurointerventional devices and techniques for MT of upper extremity arterial occlusions. Materials and Methods: A retrospective analysis of prospectively collected patient databases from four neurovascular centers was performed. Clinical and imaging data, as well as procedural parameters, were assessed. Results: Seven out of 6138 patients (incidence: 0.11%) presenting with an AIS due to the occlusion of craniocervical arteries requiring MT and a concomitant occlusion of the brachial (4/7), axillary (2/7), or ulnar (1/7) artery causing acute ULI were identified. Craniocervical MT was technically successful in all cases. Subsequent MT of the upper limb was performed using neurointerventional thrombectomy techniques, most frequently stent retriever thrombectomy (in 4/7 cases) and direct aspiration (in 7/7 cases). MT achieved successful recanalization in 6/7 cases, and the UL completely recovered in all six cases. In one case, recanalization was not successful, and the patient still had a marginally threatened extremity after the procedure, which improved after pharmacological therapy. Conclusion: In the rare case of AIS requiring MT and concomitant acute upper extremity arterial occlusion, MT of the UL arteries using neurointerventional devices and techniques is practical, effective, and safe