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BACKGROUND AND OBJECTIVE: Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcome. METHODS: We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. Classification accuracy of each gene were compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. RESULTS: WSO-SVM achieved 0.80 accuracy, 0.79 sensitivity, and 0.81 specificity for classifying EGFR; 0.71 accuracy, 0.70 sensitivity, and 0.72 specificity for classifying PDGFRA; 0.80 accuracy, 0.78 sensitivity, and 0.83 specificity for classifying PTEN; these results significantly outperformed the existing ML algorithms. Using SHAP, we found that the relative contributions of the five contrast images differ between genes, which are consistent with findings in the literature. The prediction maps revealed extensive intra-tumoral region-to-region heterogeneity within each individual tumor in terms of the alteration status of the three genes. CONCLUSIONS: This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

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Arteriovenous malformations (AVMs) are complex vascular lesions that can pose significant risk for spontaneous hemorrhage, seizures, and symptoms related to ischemia and venous hypertension.1 Microsurgical management of AVMs requires a deep understanding of the surrounding anatomy and precise identification of the lesion characteristics. We demonstrate the use of augmented reality in the localization of arterial feeders and draining veins in relation to bordering normal structures (Video 1). A 66-year-old man presented with several episodes of severe right frontal headaches. Magnetic resonance imaging revealed an AVM along the right frontal pole. Subsequent computed tomography angiography demonstrated arterial supply from the right anterior cerebral artery with venous drainage to the superior sagittal sinus. Due to the size, noneloquent location, and superficial pattern of venous drainage, the patient elected to proceed with microsurgery. A virtual planning platform was used in preparation for surgery. Augmented reality integrated with neuronavigation was used during microsurgical resection. Postoperative angiography showed complete resection of the AVM. The patient was discharged home on postoperative day 3 with no complications. He remains neurologically well at 4 months of follow-up.

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BACKGROUND: Fragmentation, disconnection, or entrapment of an in-use microcatheter during neuro-endovascular procedures is a known risk. Often a benign entity, retained catheters are not infrequently observed, but severe complications including thrombus, thromboembolic events, pseudoaneurysm, and limb ischemia have been described, necessitating retrieval. This technical case report demonstrates the safe use of an external carotid artery (ECA) approach for ligation and removal of a retained microcatheter after middle meningeal artery (MMA) embolization. This article also demonstrates the use of live intraoperative fluoroscopy as a surgical adjunct to ensure that the catheter is fully removed without any injury, shearing, or breakage during removal. METHODS: A 66-year-old male patient presented with bilateral subdural hematomas to an outside hospital. He subsequently underwent evacuation of the hematomas followed by a right-sided MMA embolization, complicated by Onyx (Medtronic, Minneapolis, MN) entrapment of the microcatheter in the MMA. The patient was asymptomatic, but there was significant concern about continuing antiplatelet/anticoagulation therapy in the presence of the subdural hematoma. We proceeded with an open surgical approach for catheter retrieval. As the catheter was withdrawn, intraoperative fluoroscopy demonstrated complete removal without any retained fragments. RESULTS: The patient recovered without event and was discharged on postoperative day 1. On follow-up the patient continued to do well without any complications from the fragment that remained in the external carotid circulation. CONCLUSIONS: This case and accompanying video demonstrates the effective use of open ECA surgical approach to retrieve the retained microcatheter after an MMA embolization. This approach allowed for safe and effective removal of the microcatheter while significantly reducing complication risks.

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Pineal region tumors are challenging lesions in terms of surgical accessibility and removal.1 The complexity is compounded by the infrequency and heterogeneity of pineal neoplasms.2,3 In Video 1, we present the case of a 39-year-old woman who presented with progressive headaches and vision impairment. She underwent microsurgical resection for a pineal parenchymal tumor of intermediate differentiation. We discuss the rationale, risks, and benefits of treatment for this patient, as well as provide a detailed overview of the alternative approaches that may be considered. Additionally, we discuss the unique anatomic considerations for each approach and include a virtual reality-compatible 3-dimensional fly-through to highlight the relationship between the tumor and relevant venous anatomy. The patient tolerated the procedure well with excellent neurologic outcome, and her follow-up imaging showed no evidence of tumor recurrence.

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Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

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Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

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BACKGROUND: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity. METHODS: Using an image-based modeling approach, we predicted T-cell abundance from serial MRIs of patients enrolled in the dendritic cell (DC) vaccine clinical trial. T-cell predictions were quantified in both the contrast-enhancing and non-enhancing regions of the imageable tumor, and changes over time were assessed. RESULTS: A subset of patients in a DC vaccine clinical trial, who had previously gone undetected, were identified as treatment responsive and benefited from prolonged survival. A mere two months after initial vaccine administration, responsive patients had a decrease in model-predicted T-cells within the contrast-enhancing region, with a simultaneous increase in the T2/FLAIR region. CONCLUSIONS: In a field that has yet to see breakthrough therapies, these results highlight the value of machine learning in enhancing clinical trial assessment, improving our ability to prospectively prognosticate patient outcomes, and advancing the pursuit towards individualized medicine.

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OBJECTIVE: We analyzed the data of patients enrolled in the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to develop and validate a model to predict the risk of aneurysmal hemorrhage. METHODS: Analysis included data from 600 patients enrolled for the HEAT trial and included single saccular aneurysms of 3-14 mm size. Baseline characteristics were compared between patients with ruptured and unruptured aneurysms. Regression analysis was performed in the training set to identify significant risk factors and was validated in the validation dataset. The complete dataset was used to formulate a scoring model in which positive and negative predictors were assigned 1 and -1 points, respectively. RESULTS: Data from 593 patients were analyzed in which 169 (28.5%) patients had ruptured aneurysms. The training (n = 297) and validation dataset (n = 296) had a comparable proportion of ruptured aneurysms (29.3% and 27.7%). Dome-to-neck ratio >2.5 (odds ratio [OR] 3.66), irregular shape (OR 3.79), daughter sac (OR 5.89), and anterior and posterior communicating artery locations (OR 3.32 and 3.56, respectively) had a higher rupture rate. Use of aspirin was associated with lower risk of hemorrhage (OR 0.16). The area under the curve from the receiver operating curve analysis was 0.88, 0.87, and 0.87 in the training, validation, and combined data set, respectively. The scoring model created a score of -1 to 2, yielding an of aneurysmal hemorrhage probability from 1.5% (score -1) to 70% (score 2). CONCLUSIONS: This prospective study identifies dome-to-neck ratio >2.5, irregular shape, presence of daughter sac, absence of aspirin use, and aneurysm location at anterior communicating and posterior communicating artery as factors associated with increased risk of hemorrhagic presentation in small- to medium-sized intracranial aneurysms. Our model provides an estimate of rupture risk based on the presence or absence of these factors.

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BACKGROUND: Pipeline embolization device (PED) deployment is a technically demanding procedure. Incomplete device expansion or deployment is one intra-operative risk, especially in patients with significant vascular tortuosity. CASE DESCRIPTION: We describe the case of a 71-year female with an unruptured left vertebral artery saccular aneurysm. Tortuosity of the arteries proximal to the aneurysm complicated deployment and the proximal end of the PED failed to expand despite several maneuvers. The inadequately expanded PED caused flow limitation in the left vertebral artery and it became imperative to achieve wall apposition of the PED. We salvaged the PED from the left vertebral artery by retrograde trans-right posterior communicating artery balloon angioplasty. CONCLUSIONS: Our case documents the successful application of the rarely used salvage strategy - anterior-to-posterior circulation retrograde rescue balloon angioplasty of an unopened PED.

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Acute ischemic stroke continues to be a major cause of death and disability globally. Although the concept of endovascular treatment of ischemic stroke is relatively new, current evidence from high-quality randomized trials suggests a significant improvement in the clinical outcome with mechanical thrombectomy up to 24 hours from the stroke onset. There has been a paradigm shift from medical management to mechanical thrombectomy which is now considered standard of care in eligible patients. Not surprisingly, there has been a constant effort to further improve stroke care in the last few years with a common goal of ultra-rapid intervention along with highly effective revascularization methods. Currently, it is one of the most dynamic and rapidly changing subspecialties in the field of medicine with significant advances in all aspects of acute stroke treatment starting from triage in the field to poststroke rehabilitation.

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