• 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.
• 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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  A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis

  Hemond, Christopher C; Deshpande, Mugdha; Berrios Morales, Idanis; Zheng, Shaokuan; Meyer, Jerrold S; Slavich, George M; Cole, Steven W (2024-06-18)

  Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.
• Teaching Diversity, Equity, Inclusion, and Health Disparities in Radiology through a Morbidity and Mortality Conference Framework

  Tai, Ryan; Mariyampillai, Matthew; Chekmeyan, Mariam; Rosen, Max P (2024-06-17)

  Referencing the objectives from the Society of General Internal Medicine’s Health Equity Commission, we created a curriculum on DEI and health care disparities tailored for radiology trainees. The capstone of this curriculum is a novel DEI and Health Disparities MMC. The residents were asked to reflect on the DEI curriculum and identify cases in which patient outcomes were less than optimal stemming from issues related to DEI and health inequities. Residents also identified cases in which radiologists and staff extended resources and time to meet the needs of vulnerable patients.
• A hydrophobic core stabilizes the residual structure in the RRM2 intermediate state of the ALS-linked protein TDP-43 [preprint]

  Mackness, Brian C; Morgan, Brittany R; Deveau, Laura M; Kathuria, Sagar V; Zitzewitz, Jill A; Massi, Francesca (2024-06-12)

  Folding intermediates mediate both protein folding and the misfolding and aggregation observed in human diseases, including amyotrophic lateral sclerosis (ALS), and are prime targets for therapeutic interventions. In this study, we identified the core nucleus of structure for a folding intermediate in the second RNA recognition motif (RRM2) of the ALS-linked RNA-binding protein, TDP-43, using a combination of experimental and computational approaches. Urea equilibrium unfolding studies revealed that the RRM2 intermediate state consists of collapsed residual secondary structure localized to the N-terminal half of RRM2, while the C-terminus is largely disordered. Steered molecular dynamics simulations and mutagenesis studies yielded key stabilizing hydrophobic contacts that, when mutated to alanine, severely disrupt the overall fold of RRM2. In combination, these findings suggest a role for this RRM intermediate in normal TDP-43 function as well as serving as a template for misfolding and aggregation through the low stability and non-native secondary structure.
• Correction of multiplexing artefacts in multi-pinhole SPECT through temporal shuttering, de-multiplexing of projections, and alternating reconstruction

  Pells, Sophia; Zeraatkar, Navid; Kalluri, Kesava S; Moore, Stephen C; May, Micaehla; Furenlid, Lars R; Kupinski, Matthew A; Kuo, Phillip H; King, Michael A (2024-06-06)

  Objective.Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images.Approach.Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics.Main results.Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR.Significance.The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images.
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  Case report: Nocturnal low-frequency stimulation of the centromedian thalamic nucleus improves sleep quality and seizure control

  Suresh, Surya; Chaitanya, Ganne; Kachhvah, Ajay Deep; Vashin, Vladimir; Saranathan, Manojkumar; Pati, Sandipan (2024-06-05)

  Sleep disturbances and drug-resistant seizures significantly impact people with idiopathic generalized epilepsy (IGE). Thalamic deep brain stimulation (DBS) offers potential treatment, but its effect on sleep and seizure control needs clarification. In this study, we combined wearable sleep monitoring with electroencephalogram (EEG) confirmation to investigate the impact of nocturnal centromedian nucleus (CM) DBS parameters in a patient with drug-resistant IGE. We found that high-frequency (125 Hz) CM stimulation during sleep severely disrupted sleep macro architecture and exacerbated seizures. Conversely, switching to low-frequency (10 Hz) stimulation enhanced both sleep quality and seizure control. This study underscores the critical need to personalize DBS settings, tailoring them to individual patients' sleep patterns to maximize therapeutic benefits. While larger-scale trials are needed, our findings pave the way for patient-centric approaches to thalamic neuromodulation, offering a transformative path to improve treatment outcomes and quality of life for those with refractory epilepsy.
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  Evaluation of flow diverters for cerebral aneurysm therapy: recommendations for imaging analyses in clinical studies, endorsed by ESMINT, ESNR, OCIN, SILAN, SNIS, and WFITN

  Fiehler, Jens; Ortega-Gutierrez, Santiago; Anagnostakou, Vania; Cortese, Jonathan; Cekirge, H Saruhan; Fiorella, David; Hanel, Ricardo; Kulcsar, Zsolt; Lamin, Saleh; Liu, Jianmin; et al. (2024-06-02)

  Background: Multiple studies and meta-analyses have described the technical and clinical outcomes in large cohorts of aneurysm patients treated with flow diverters (FDs). Variations in evaluation methodology complicate making comparisons among studies, hinder understanding of the device behavior, and pose an obstacle in the assessment of further advances in FD therapy. Methods: A multidisciplinary panel of neurointerventionalists, imaging experts, and neuroradiologists convened with the goal of establishing consensus recommendations for the standardization of image analyses in FD studies. Results: A standardized methodology is proposed for evaluating and reporting radiological outcomes of FD treatment of intracranial aneurysms. The recommendations include general imaging considerations for clinical studies and evaluations of longitudinal changes, such as neointimal lining and stenosis. They cover standards for classification of aneurysm location, morphology, measurements, as well as the assessment of aneurysm occlusion, wall apposition, and neck coverage. These reporting standards further define four specific braid deformation patterns: foreshortening, fish-mouthing, braid bump deformation, and braid collapse, collectively termed 'F2B2'. Conclusions: When widely applied, standardization of methods of measuring and reporting outcomes will help to harmonize the assessment of treatment outcomes in clinical studies, help facilitate communication of results among specialists, and help enable research and development to focus on specific aspects of FD techniques and technology.
• ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update

  Niell, Bethany L; Jochelson, Maxine S; Amir, Tali; Brown, Ann; Adamson, Megan; Baron, Paul; Bennett, Debbie L; Chetlen, Alison; Dayaratna, Sandra; Freer, Phoebe E; et al. (2024-06-01)

  Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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  Oxygen Sensor-Guided Fine Needle Biopsy Studies of Human Cancer Xenografts in Mice [preprint]

  McDonald, Robert C; Fischer, Andrew H; Rusckowski, Mary (2024-06-01)

  An oxygen sensor-mounted fine-needle biopsy tool was used for in vivo measurement of oxygen levels in tumor xenografts. The system provides a means of measuring the oxygen content in harvested tumor tissue from specific locations. Oxygen in human tumor xenografts in a murine model was observed for over 1 min. Tissues were mapped in relation to oxygen tension (pO2) readings and sampled for conventional cytological examination. Careful modeling of the pO2 readings over 60 seconds yielded a diffusion coefficient for oxygen at the sensor tip, providing additional diagnostic information about the tissue before sampling. Oxygen level measurement may provide a useful adjunct to the use of biomarkers in tumor diagnosis.
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  Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability

  Tanaka, Kanta; Yamagami, Hiroshi; Qureshi, Muhammad M; Uchida, Kazutaka; Siegler, James E; Nogueira, Raul G; Yoshimura, Shinichi; Sakai, Nobuyuki; Martinez-Majander, Nicolas; Nagel, Simon; et al. (2024-05-30)

  Background and purpose: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). Results: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). Conclusion: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.
• I saw the swirl sign: Acute extravasation of blood within a hematoma

  Botros, Mina B; Puri, Ajit S; Singh, Jasmeet; Kuhn, Anna Luisa (2024-05-25)

  The swirl sign is a finding on non-contrast computed tomography (CT) scans that represents an acute extravasation of blood into a hematoma filled with clotted blood. In it, a "swirl" of active bleeding within a body of acutely clotted blood is noted as a hypodense accumulation within a hyperdense fluid collection. Here, we describe a case in which a 35-year-old female presents unresponsive with a Glasgow Coma Scale score of 3 and is ultimately found to have a large frontal intraparenchymal hematoma with intraventricular extension and an area of low attenuation within the hyperattenuating fluid collection on CT, otherwise known as the swirl sign. This radiographic sign has been associated with hematoma expansion, worse clinical outcomes as measured by the Glasgow Outcome Scale, and higher mortality rates. As such, all patients suspected to have intracranial bleeds should have CT imaging done as soon as possible. When the swirl sign is identified on CT, providers are clued in to the risk of clinical deterioration and the urgent need for surgical evaluation.
• Facilitating Culturally Competent Breast Imaging Care in South Asian Patients

  Sharma, Nidhi; Mehta, Tejas S; Wahab, Rifat A; Patel, Miral M (2024-05-24)

  South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations.
• A Case Study Identifying Barriers to Breast Cancer Screening and Strategies for Improved Access and Participation in an Underserved Community

  Vijayaraghavan, Gopal R (2024-05-20)

  A complex interplay of racial, ethnic, and social determinants are the drivers for disparity in access to screening, quality of care and health outcomes in diverse populations.
• Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke

  Mujanovic, Adnan; Strbian, Daniel; Demeestere, Jelle; Marto, João Pedro; Puetz, Volker; Nogueira, Raul G; Abdalkader, Mohamad; Nagel, Simon; Raymond, Jean; Ribo, Marc; et al. (2024-05-17)

  Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. Results: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). Conclusion: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. Trial registration number: clinicaltrials.gov; Unique identifier: NCT04096248.
• Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke

  Demeestere, Jelle; Qureshi, Muhammad M; Vandewalle, Lieselotte; Wouters, Anke; Strbian, Daniel; Nogueira, Raul G; Nagel, Simon; Yamagami, Hiroshi; Puetz, Volker; Abdalkader, Mohamad; et al. (2024-05-15)

  Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.
• Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe

  Pereira, Vitor M; Lylyk, Pedro; Cancelliere, Nicole; Lylyk, Pedro N; Lylyk, Ivan; Anagnostakou, Vania; Bleise, Carlos; Nishi, Hidehisa; Epshtein, Mark; King, Robert M; et al. (2024-05-15)

  Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.
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  Mid-term safety and efficacy in small intracranial aneurysm coiling: results from TARGET nano prospective independent core lab adjudicated multicenter registry

  Ashouri, Yazan; Paul, Alexandra R; Puri, Ajit S; Liaw, Nicholas; Majjhoo, Aniel; Taqi, Asif; Rai, Ansaar; Badruddin, Aamir; Alshekhlee, Amer; Naravetla, Bharath; et al. (2024-05-13)

  Background: The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms. Methods: The TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with de novo intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length). Results: 150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%, p < 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%). Conclusion: In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.

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