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BackgroundThe Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the communicating artery segment.MethodsThe Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms (SCENT) trial is an international, multicenter, prospective, non-randomized trial comparing the outcomes of Surpass flow diverter treatment with historic control designed to evaluate the effectiveness and safety of Surpass for the treatment of wide neck (≥4 mm) large or giant intracranial aneurysms ≥10 mm. The primary effectiveness endpoint is the percentage of subjects with 100% aneurysm occlusion without significant stenosis of the parent artery and without retreatment of the target aneurysm at 12 months. The primary safety endpoint is the percentage of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. We report the effectiveness and safety of flow diversion in the subgroup of posterior communicating artery (PComA) aneurysms.ResultsOf the 180 patients treated, 38 harbored a PComA aneurysm. Mean aneurysm size was 12.2 mm and mean neck width was 4.8 mm. The mean number of Surpass devices used was 1.1 per procedure, with 94.7% of aneurysms treated with one flow diverter. The 12 month primary effectiveness rate was 73.7% (28/38). At 36 months, 68.4% (26/38) of aneurysms remained completely occluded. The 12 month major ipsilateral stroke or neurological death rate was 10.5%. No patients with PComA occlusion after flow diverter placement (54.5%) had clinical sequelae.ConclusionsSCENT demonstrated acceptable 12 month effectiveness of flow diversion in PComA aneurysms. Despite associated PComA occlusions in many cases, arterial occlusions were clinically silent.Trial registration numberURL: https://www.clinicaltrials.gov. Unique identifier: NCT01716117.

Expansions of a G(4)C(2) repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset neurodegenerative disorders. Using C9-ALS/FTD patient derived cells and C9ORF72 BAC transgenic mice, we have generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of G(4)C(2) repeat containing transcripts and effectively suppress tissue levels of polyGP dipeptides. ASOs with reduced phosphorothioate content showed improved tolerability without sacrificing efficacy. In a single patient harboring mutant C9ORF72 with the G(4)C(2) repeat expansion, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of CSF polyGP. This report provides insight into the impact of nucleic acid chemistry on toxicity and for the first time demonstrates the feasibility of clinical suppression of the C9ORF72 gene. Further clinical trials will be required to demonstrate safety and efficacy of this therapy in patients with C9ORF72 gene mutations.

PURPOSE: To develop multimodality imaging techniques for measuring epidermal growth factor receptor (EGFR) as a therapy-relevant and metastasis-associated molecular marker in triple-negative mammary adenocarcinoma metastases. MATERIALS AND METHODS: An orthotopic bone metastasis EGFR-positive, triple-negative breast cancer (TNBC) model in rats was used for bioluminescence imaging, SPECT/CT, PET/CT, and MRI with quantitative analysis of transcripts (n = 22 rats). Receptor-specific MRI of EGFR expression in vivo was performed by acquiring spin-echo T1-weighted images after sequential administration of a pair of anti-EGFR antigen binding fragments, F(ab’)(2), conjugated to either horseradish peroxidase or glucose oxidase, which have complementing activities, as well as paramagnetic (gadolinium[III]-mono-5-hydroxytryptamide of 2,2′,2′′-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid, or Gd-5HT-DOTAGA) or positron-emitting (gallium 68-5HT-DOTAGA) substrates for MRI and PET/CT imaging, respectively. EGFR expression was confirmed by quantitative reverse transcriptase polymerase chain reaction and immunohistochemical analyses to compare with image findings. RESULTS: After surgical intraarterial delivery of TNBC cells, rats developed tumors that diverged into either rapidly growing osteolytic or slow-growing nonosteolytic tumors. Both tumor types showed receptor-specific initial MRI signal enhancement (contrast-to-noise ratio) that was three to six times higher than that of normal bone marrow (29.4 vs 4.9; P < .01). Micro PET/CT imaging of EGFR expression demonstrated a high level of heterogeneity with regional uptake of the tracer, which corresponded to region-of-interest MRI signal intensity elevation (121.1 vs 93.3; P < .001). Analysis of metastases with corroboration of imaging results showed high levels of EGFR protein and messenger RNA, or mRNA, expression in the invasive tumor. CONCLUSION: Convergence of multimodal molecular receptor imaging enabled comprehensive assessment of EGFR overexpression in an orthotopic model of TNBC metastasis. Keywords: Animal Studies, Molecular Imaging-Cancer, MR-Contrast Agent, Radionuclide Studies, Skeletal-Appendicular, Metastases Supplemental material is available for this article. © RSNA, 2021

Objective: Mechanical thrombectomy using stent-retriever technology provides acute ischemic stroke patients with beneficial treatment of emergent large vessel occlusion. Still, the disparity between recanalization rates and clinical outcomes calls for enhanced device designs and treatment strategies with better reperfusion efficiency. Intuitively, sufficient device integration with the embolus is pursued to maximize chances of first-pass success, thereby limiting clot fragmentation and intimal trauma during extensive clot manipulation. Our aim was to develop an imaging-based measure of device integration in reproducible phantom experiments that could help identifying differences in aspects of thrombectomy procedures that may be related to angiographic and clinical outcomes. Methods: Deployment variations of the Trevo(TM) ProVue/XP retriever were tested in an in-vitro model system that mimicked a MCA-occlusion with a silicone vascular replica and two visible clot models (soft elastic, and hard inelastic) with 8 trials/group. High-resolution cone-beam CT imaging was performed prior to retriever retraction. An image processing pipeline was devised that used level-set segmentation, path-tracing, and Steiner circumellipse fitting to extract and determine the interior volumes of the clot and the three visible wires. Clot Integration Factor (CIF) was calculated as the ratio of the volume of clot-device intersection to the clot volume. Results: Example of the device, its wires, and the clot: Average clot volumes were 90.4±12.2mm3. CIF was significantly different for two deployment variations when the device engaged a hard clot (difference between means, 95%CI=[0.003,0.187], p=0.043), but not a soft clot model (95%CI=[-0.152,0.263], p=0.567). Conclusion: In-vitro imaging-based quantification of clot integration can detect differences in deployment configuration relative to a clot, which may support procedural and design improvements.