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  A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP

  Benatti, Hector Ribeiro; Anagnostakou, Vania; Taghian, Toloo; Hall, Erin F; Nath, Sarah; Heilman, Carl B; Beneduce, Brandon M; Leporati, Anita; Raskett, Christopher M; Epshtein, Mark; et al. (2024-08-26)

  Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.
• Normative Modeling of Thalamic Nuclear Volumes and Characterization of Lateralized Volume Alterations in Alzheimer's Disease Versus Schizophrenia

  Young, Taylor R; Kumar, Vinod Jangir; Saranathan, Manojkumar (2024-08-23)

  Background: Thalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer's disease (AD) and schizophrenia. The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in schizophrenia and AD. Methods: Volumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 MRI data using a state-of-the-art novel segmentation method in healthy control subjects (n=2374) and early mild cognitive impairment (MCI, n=211), late MCI (n=113), AD (n=88), and schizophrenia (n=168). Normative models for each nucleus were generated from healthy control subjects while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z|>1.96) and z-score distributions were compared across phenotypes. Z-scores were associated with clinical descriptors. Results: Increased infranormal and decreased supranormal z-scores were observed in schizophrenia and AD. Z-score shifts representing reduced volumes were observed in most nuclei in schizophrenia and AD with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD with evidence of a left-sided preference in early MCI while a predilection for right thalamic nuclei was observed in schizophrenia. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations. Conclusion: In AD, thalamic nuclei are more severely and symmetrically affected while in schizophrenia, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of schizophrenia and is affected early in the disease course.
• Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy

  Yedavalli, Vivek; Salim, Hamza; Musmar, Basel; Adeeb, Nimer; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; et al. (2024-08-19)

  Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.
• Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database

  Musmar, Basel; Adeeb, Nimer; Gendreau, Julian; Horowitz, Melanie Alfonzo; Salim, Hamza Adel; Sanmugananthan, Praveen; Aslan, Assala; Brown, Nolan J; Cancelliere, Nicole M; McLellan, Rachel M; et al. (2024-08-10)

  Background: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging. Objective: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/. Conclusion: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.
• Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion

  Dmytriw, Adam A; Ghozy, Sherief; Salim, Hamza Adel; Musmar, Basel; Siegler, James E; Kobeissi, Hassan; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; et al. (2024-08-06)

  Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.
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  Investigating therapeutic nonsense suppression in a neurofibromatosis mouse model

  Wu, Chan; Shazeeb, Mohammed Salman; Mangkalaphiban, Kotchaphorn; Han, George; Peker, Ahmet; Rentiya, Zubir S; Gounis, Matthew J; Jacobson, Allan (2024-08-04)

  Neurofibromatosis type 1 (NF1) is a human genetic disorder caused by variants in the NF1 gene. Plexiform neurofibromas, one of many NF1 manifestations, are benign peripheral nerve sheath tumors occurring in up to 50% of NF1 patients. A substantial fraction of NF1 pathogenetic variants are nonsense mutations, which result in the synthesis of truncated non-functional NF1 protein (neurofibromin). To date, no therapeutics have restored neurofibromin expression or addressed the consequences of this protein's absence in NF1 nonsense mutation patients, but nonsense suppression is a potential approach to the problem. Ataluren is a small molecule drug that has been shown to stimulate functional nonsense codon readthrough in several models of nonsense mutation diseases, as well as in Duchenne muscular dystrophy patients. To test ataluren's potential applicability in nonsense mutation NF1 patients, we evaluated its therapeutic effects using three treatment regimens in a previously established NF1 patient-derived (c.2041C > T; p.Arg681X) nonsense mutation mouse model. Collectively, our experiments indicate that: i) ataluren appeared to slow the growth of neurofibromas and alleviate some paralysis phenotypes, ii) female Nf1-nonsense mutation mice manifested more severe paralysis and neurofibroma phenotypes than male mice, iii) ataluren doses with apparent effectiveness were lower in female mice than in male mice, and iv) age factors also influenced ataluren's effectiveness.
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  Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis

  Musmar, Basel; Salim, Hamza Adel; Adeeb, Nimer; Aslan, Assala; Aljeradat, Bahaa; Diestro, Jose Danilo Bengzon; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; Dibas, Mahmoud; et al. (2024-07-31)

  The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.
• Off-Label use of Woven EndoBridge device for intracranial brain aneurysm treatment: Modeling of occlusion outcome

  Essibayi, Muhammed Amir; Jabal, Mohamed Sobhi; Musmar, Basel; Adeeb, Nimer; Salim, Hamza; Aslan, Assala; Cancelliere, Nicole M; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; et al. (2024-07-26)

  Introduction: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes. Methods: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95 % confidence intervals (CI) were reported. Results: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95 % CI 1.25-2.82), larger neck diameter (OR 1.69, 95 % CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95 % CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors. Conclusion: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed.
• Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy

  Yedavalli, Vivek S; Salim, Hamza Adel; Musmar, Basel; Adeeb, Nimer; Essibayi, Muhammed Amir; ElNaamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kuhn, Anna Luisa; Khalife, Jane; et al. (2024-07-24)

  Background: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. Methods: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. Results: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). Conclusion: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.
• Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study

  Salim, Hamza Adel; Yedavalli, Vivek; Musmar, Basel; Adeeb, Nimer; E L Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; et al. (2024-07-23)

  Background: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. Methods: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. Results: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). Conclusion: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.
• Selective brain cooling with a novel catheter reduces infarct growth after recanalization in a canine large vessel occlusion model

  King, Robert M; Anagnostakou, Vania; Shazeeb, Mohammed Salman; Hornibrook, Shannon; Mitchell, Jennifer; Epshtein, Mark; Raskett, Christopher M; Henninger, Nils; Puri, Ajit S; Merrill, Thomas L; et al. (2024-07-23)

  Background: Therapeutic hypothermia has shown potential in cardiac intervention for years; however, its adoption into the neurovascular space has been limited. Studies have pointed to slow cooling and limited depth of hypothermia yielding negative outcomes. Here we present an insulated catheter that allows for consistent infusion of chilled saline directly to the brain. Direct delivery of cold saline allows a faster depth of hypothermia, which could have a benefit to the growth of ischemic lesions. Methods: Ten canines were randomized to either receive selective brain cooling or no additional therapy. Eight animals were successfully enrolled (n = 4 per group). Each animal underwent a temporary middle cerebral artery occlusion (MCAO) for a total of 45 min. Five minutes prior to flow restoration, chilled saline was injected through the ipsilateral internal carotid artery using an insulated catheter to ensure delivery temperature. The treatment continued for 20 min, after which the animal was transferred to an MRI scanner for imaging. Results: Of the 8 animals that were successfully enrolled in the study, 3 were able to survive to the 30-day endpoint with no differences between the cooled and control animals. There was no difference in the initial mean infarct size between the groups; however, animals that did not receive cooling had infarcts continuing to progress more rapidly after the MCAO was removed (13.8% vs 161.3%, p = 0.016, cooled vs control). Conclusions: Selective hypothermia was able to reduce the post-MCAO infarct progression in a canine model of temporary MCAO.
• Comparative Efficacy of Flow Diverter Devices in the Treatment of Carotid Sidewall Intracranial Aneurysms: a Retrospective, Multicenter Study

  Dmytriw, Adam A; Salim, Hamza Adel; Musmar, Basel; Cancelliere, Nicole M; Griessenauer, Christoph J; Regenhardt, Robert W; Jones, Jesse; Tutino, Vincent; Hasan, Zuha; Limbucci, Nicola; et al. (2024-07-18)

  Background: The comparative efficacy and safety of first-generation flow diverters (FDs), Pipeline Embolization Device (PED) (Medtronic, Irvine, California), Silk (Balt Extrusion, Montmorency, France), Flow Re-direction Endoluminal Device (FRED) (Microvention, Tustin, California), and Surpass Streamline (Stryker Neurovascular, Fremont, California), is not directly established and largely inferred. Purpose: This study aimed to compare the efficacy of different FDs in treating sidewall ICA intracranial aneurysms. Methods: We conducted a retrospective review of prospectively maintained databases from eighteen academic institutions from 2009-2016, comprising 444 patients treated with one of four devices for sidewall ICA aneurysms. Data on demographics, aneurysm characteristics, treatment outcomes, and complications were analyzed. Angiographic and clinical outcomes were assessed using various imaging modalities and modified Rankin Scale (mRS). Propensity score weighting was employed to balance confounding variables. The data analysis used Kaplan-Meier curves, logistic regression, and Cox proportional-hazards regression. Results: While there were no significant differences in retreatment rates, functional outcomes (mRS 0-1), and thromboembolic complications between the four devices, the probability of achieving adequate occlusion at the last follow-up was highest in Surpass device (HR: 4.59; CI: 2.75-7.66, p < 0.001), followed by FRED (HR: 2.23; CI: 1.44-3.46, p < 0.001), PED (HR: 1.72; CI: 1.10-2.70, p = 0.018), and Silk (HR: 1.0 ref. standard). The only hemorrhagic complications were with Surpass (1%). Conclusion: All the first-generation devices achieved good clinical outcomes and retreatment rates in treating ICA sidewall aneurysms. Prospective studies are needed to explore the nuanced differences between these devices in the long term.
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  CLEAR Thrombectomy Score: An Index to Estimate the Probability of Good Functional Outcome With or Without Endovascular Treatment in the Late Window for Anterior Circulation Occlusion

  Siegler, James E; Koneru, Manisha; Qureshi, Muhammad M; Doheim, Mohamed; Nogueira, Raul G; Martinez-Majander, Nicolas; Nagel, Simon; Penckofer, Mary; Demeestere, Jelle; Puetz, Volker; et al. (2024-07-09)

  Background: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management. Methods and results: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all Pinteraction<0.001), with greater benefit favoring patients with lower and midrange scores. Conclusions: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window. Registration: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.
• Increasing magic number and other trends in diagnostic radiology NRMP match data

  Taros, Trenton; Zoppo, Christopher T; Camargo, Anthony M; DeBenedectis, Carolynn M (2024-07-09)

  The magic number, or number of ranks needed to achieve a greater than 90 % chance of matching, has not been investigated for diagnostic radiology (DR). Somewhat reflective of a field's changing competitiveness, this individual metric can be useful for reassuring applicants or identifying a need to reach out to mentors. The NRMP's Charting Outcomes in the Match was accessed over the previous 10 cycles to assess changes to magic number and other match-related metrics. Over the last 10 cycles, there has been an increase in magic number for prospective radiologists. Based on the most 2022 recent report, the magic number was 14 compared to 5 and 2 in 2014 and 2016 respectively. Compared to the average US MD senior, those applying into DR were significantly more likely to match in 2014, 2016 and 2020 (p < 0.01 for all), and significantly less likely to match in 2018 and 2022 (p = 0.03 and p < 0.01, respectively). This trend has had important consequences for applicants and programs as the incentive to apply more widely grows. The increasing magic number demonstrates increasing competitiveness in the field, which might be due to a positive job market, changing medical student preferences, or increased access to radiology electives and mentors. The 2024 Charting Outcomes document will be the first to include data from a class almost entirely affected by the change to a pass/fail Step1 and the new preference signaling supplement. It is currently unclear how either change will affect the overall competitiveness of the field and the magic number.
• Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study

  Mastorakos, Panagiotis; Naamani, Kareem El; Adeeb, Nimer; Lan, Mathews; Castiglione, James; Khanna, Omaditya; Ghosh, Ritam; Bengzon Diestro, Jose Danilo; Dibas, Mahmoud; McLellan, Rachel M; et al. (2024-07-08)

  Background and purpose: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. Materials and methods: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. Results: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. Conclusions: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.
• Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6

  Kühn, Anna Luisa; Puri, Ajit S; Salim, Hamza Adel; Musmar, Basel; Ghozy, Sherief; Siegler, James; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; et al. (2024-07-05)

  Background: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. Purpose: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. Materials and methods: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. Results: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. Conclusion: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.
• Subacute Cerebral Infarct: An Unusual Cause of Radiotracer Uptake at 18 F-PSMA PET/CT

  Jain, Vaibhav; McIntosh, Lacey J (2024-07-05)

  Prostate-specific membrane antigen (PSMA) PET/CT has become an unparalleled modality in the diagnosis of primary and recurrent prostatic adenocarcinoma, often revealing sites of disease that were previously invisible on conventional imaging. In this 78-year-old man with suspected prostate cancer recurrence, PSMA PET/CT revealed focal radiotracer uptake in the brain, which would ordinarily raise suspicion for metastases, but was a false positive in the setting of a recent stroke. Increased PSMA uptake has been reported in subacute infarcts and primary and secondary brain tumors. Careful history and comparison with prior imaging are vital to avoid false-positive diagnosis in such patients.
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  X-ray Attenuating Vesicles with Neutrophil Extracellular Trap (NET) Specificity: Synthesis and Testing in a Model System

  Epshtein, Mark; Gounis, Matthew J; Bogdanov, Alexei A. Jr. (2024-06-24)

  X-ray attenuating contrast agents for imaging thrombi directly during endovascular thrombectomy (EVT) are urgently needed for shortening the wait time for treatment and for reducing the chances of blood clot fragmentation. Neutrophil extracellular traps (NETs) are a product of an innate immune system response by which neutrophils release decondensed chromatin strands decorated with granule and cytosolic proteins, including neutrophil elastase and citrullinated histone H3 (CitH3). NETs are frequently found within fibrous thrombi in pathology and represent a promising target for thrombi-specific imaging agents due to their common occurrence in human cerebrovascular thrombi. We designed and tested 200 nm lipid vesicles (LV) formulated in the presence of a combination of hydrophilic and hydrophobic computed tomography (CT) contrast agents with resultant efficacy of X-ray attenuation corresponding to 312 ± 54 mg/mL iodine. The LV incorporated trans-cyclooctene-terminated pegylated distearoylphosphatidylethanolamine (TCO-PEG-DSPE) for rapid conjugation of methyltetrazine(mTz)-modified monoclonal immunoglobulin G (IgG) with anti-citH3 binding specificity. By using differential fluorescent labeling of the antibody and lipid components, we determined that 80 ± 3% of mTz-linked IgG coprecipitated with the LV after conjugation in contrast to 0.1-0.2% of control IgG. The engineered NET-specific LV were tested in vitro using differentiated human HL60 promyeloblasts (dHL60) as a standard model of NETing neutrophils. Using fibrin meshwork-incorporated dHL60 as well as monolayer cell cultures, we determined that anti-citH3 LV showed specific and high-affinity binding to dHL60 cells, which were stimulated to undergo NETosis. This work suggests the high promise of NET-specific agents in providing thrombus-specific imaging contrast during EVT.
• Multicenter early United States feasibility study and periprocedural safety of LVIS EVO for the treatment of unruptured intracranial aneurysms

  Kayan, Yasha; Delgado Almandoz, Josser E; Copelan, Alexander; Matouk, Charles; Chaudry, M Imran; Altschul, David; Essibayi, Muhammed Amir; Goren, Oded; Yim, Benjamin; Tsappidi, Sam; et al. (2024-06-21)

  Background: Stent development has focused recently on low-profile, self-expandable stents compatible with 0.0165 inch microcatheters. The LVIS EVO is the second-generation version of the Low-Profile Visualized Intraluminal Support (LVIS) with improved visibility and resheathability. The LVIS EVO underwent a limited premarket release (PMR) in December 2023. This study aims to report the early safety and feasibility experience with the LVIS EVO stent for the treatment of intracranial aneurysms in the United States (US). Methods: This was a multicenter, retrospective, observational study evaluating patients who underwent treatment of an intracranial aneurysm with an LVIS EVO stent after the limited PMR. All physicians who had placed an LVIS EVO stent were asked to input their cases after institutional review board approval was obtained. The data were then sent to a single center for analysis. Any patient aged 18 years or older who underwent treatment of an intracranial aneurysm with a LVIS EVO stent in the US was included from the initial PMR in December 2023 until April 2024. Patient age (or ≤90 years old), sex, preoperative modified Rankin Scale (mRS), aneurysm location, aneurysm measurements, and information about preoperative antiplatelet management were all collected. Data on periprocedural complications, 30-day mortality, discharge mRS, and length of stay were also collected. Results: Some 53 patients with 55 aneurysms underwent treatment with the LVIS EVO stent at 15 institutions. All aneurysms were unruptured. The most common location was the anterior communicating artery (35%) followed by the middle cerebral artery bifurcation (31%). All patients were on dual antiplatelet therapy. The average aneurysm size was 5.2 mm with a neck size of 3.7 mm. The smallest distal parent vessel size was 1.2 mm and 36% of stents were deployed in distal parent vessels <2 mm. All (100%) cases had successful deployment and the stent was repositioned in 10% of cases. A single stent was utilized in 91% of cases. Coils were placed in 48 cases (87.2%) and a microcatheter was jailed in 98% of those cases. Immediate Raymond Roy (RR) Class I occlusion was obtained in 33%, Class II in 22%, Class IIIa in 37%, and Class IIIb in 8% of cases. There were no delayed thromboembolic or hemorrhagic complications. Conclusions: The LVIS EVO is a braided, self-expanding, retrievable stent with enhanced visibility and smaller cell size. The drawn filled tube (DFT) technology results in improved visibility of the stent, allowing for more controlled stent positioning and visualization of vessel wall apposition. All cases in our series had complete neck coverage and good wall apposition. There were no thromboembolic or hemorrhagic complications.
• Integrated cardio-thoracic imaging curriculum for residents: Design, implementation, and analysis of test and evaluation results

  Barile, Maria; Kifjak, Daria; El Kaddouri, Bilal; Bankier, Alexander A (2024-06-20)

  As the field of cardiac imaging has demonstrated exceptional growth over the past several decades, radiology departments and residency programs have struggled to integrate cardiac imaging instruction into training curricula. Purpose: To create an integrated cardio-thoracic teaching and lecture curriculum and resident rotation in accordance with AGGME and Society of Thoracic Radiology (STR) guidelines. Materials and methods: Consecutive PGY-2 to PGY-4 residents (n = 14) rotating through our Cardiothoracic Imaging (CTI) section from 1/1/2021 to 04/18/2022 were give pre- and post- rotation tests of knowledge and feedback evaluations. Attending feedback of the curriculum was obtained at 3-months and 9-months post curriculum implementation. A Wilcxon test was used to evaluate differences in improvement between pre- and post- rotation resident feedback scores, test scores for thoracic and cardiac test questions in addition to attending feedback scores at 3 and 9-months post curriculum implementation. Results: The overall post-rotation scores in addition to thoracic only and cardiac only scores improved, with the difference between improved versus stable or decreased scores being statistically significant overall (P = 0.039) and for cardiac scores (P = 0.003), but not for thoracic scores (P = 0.22). The overall (P = 0.002), thoracic (P = 0.027), and cardiac (P = 0.026) resident feedback scores were significantly improved post-rotation. Similarly, the overall attending feedback scores significantly improved over time (P = 0.021). Conclusion: An integrated Cardio-thoracic Imaging teaching curriculum was well received by both residents and attendings with significant improvement in post rotation feedback scores by both groups. Moreover, residents demonstrated improved scores on knowledge tests post rotation.

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