Association of Carotid Artery Disease with Collateralization and Infarct Growth in Patients with Acute Middle Cerebral Artery Occlusion.

BACKGROUND AND PURPOSE: Collaterals are important in large vessel occlusions (LVO), but the role of carotid artery disease (CAD) in this context remains unclear. This study aimed to investigate the impact of CAD on intracranial collateralization and infarct growth after thrombectomy in LVO. MATERIALS AND METHODS: All patients who underwent thrombectomy due to M1 segment occlusion from 01/2015 to 12/2021 were retrospectively included. Internal carotid artery stenosis according to NASCET was assessed on the affected and nonaffected sides. Collaterals were assessed according to the Tan score. Infarct growth was quantified by comparing ASPECTS on follow-up imaging with baseline ASPECTS. RESULTS: In total, 709 patients were included, 118 (16.6%) of whom presented with CAD (defined as severe stenosis ≥70% or occlusion ipsilaterally), with 42 cases (5.9%) being contralateral. Good collateralization (Tan 3) was present in 56.5% of the patients with ipsilateral CAD and 69.1% of the patients with contralateral CAD. The ipsilateral stenosis grade was an independent predictor of good collateral supply (adjusted OR: 1.01; NASCET point, 95% CI: 1.00-1.01; P = .009), whereas the contralateral stenosis grade was not (P = .34). Patients with ipsilateral stenosis of ≥70% showed less infarct growth (median ASPECTS decay: 1; IQR: 0-2) compared with patients with 0%-69% stenosis (median: 2; IQR: 1-3) (P = .005). However, baseline ASPECTS was significantly lower in patients with stenosis of 70%-100% (P < .001). The results of a multivariate analysis revealed that increasing ipsilateral stenosis grade (adjusted OR: 1.0; 95% CI: 0.99-1.00; P = .004) and good collateralization (adjusted OR: 0.5; 95% CI: 0.4-0.62; P < .001) were associated with less infarct growth. CONCLUSIONS: CAD of the ipsilateral ICA is an independent predictor of good collateral supply. Patients with CAD tend to have larger baseline infarct size but less infarct growth.

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

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

Cortical atrophy on baseline computed tomography imaging predicts clinical outcome in patients undergoing endovascular treatment for acute ischemic stroke.

OBJECTIVE: Multiple variables beyond the extent of recanalization can impact the clinical outcome after acute ischemic stroke due to large vessel occlusions. Here, we assessed the influence of small vessel disease and cortical atrophy on clinical outcome using native cranial computed tomography (NCCT) in a large single-center cohort. METHODS: A total of 1103 consecutive patients who underwent endovascular treatment (EVT) due to occlusion of the middle cerebral artery territory were included. NCCT data were visually assessed for established markers of age-related white matter changes (ARWMC) and brain atrophy. All images were evaluated separately by two readers to assess the inter-observer variability. Regression and machine learning models were built to determine the predictive relevance of ARWMC and atrophy in the presence of important baseline clinical and imaging metrics. RESULTS: Patients with favorable outcome presented lower values for all measured metrics of pre-existing brain deterioration (p < 0.001). Both ARWMC (p < 0.05) and cortical atrophy (p < 0.001) were independent predictors of clinical outcome at 90 days when controlled for confounders in both regression analyses and led to a minor improvement of prediction accuracy in machine learning models (p < 0.001), with atrophy among the top-5 predictors. CONCLUSION: NCCT-based cortical atrophy and ARWMC scores on NCCT were strong and independent predictors of clinical outcome after EVT. CLINICAL RELEVANCE STATEMENT: Visual assessment of cortical atrophy and age-related white matter changes on CT could improve the prediction of clinical outcome after thrombectomy in machine learning models which may be integrated into existing clinical routines and facilitate patient selection. KEY POINTS: • Cortical atrophy and age-related white matter changes were quantified using CT-based visual scores. • Atrophy and age-related white matter change scores independently predicted clinical outcome after mechanical thrombectomy and improved machine learning-based prediction models. • Both scores could easily be integrated into existing clinical routines and prediction models.

MR microscopy to assess clot composition following mechanical thrombectomy predicts recanalization and clinical outcome.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic value is attributed to it, and MT is performed in a standardized 'non-personalized' approach. Whether different clot compositions are associated with intrinsic likelihoods of recanalization success or treatment outcome is unknown. METHODS: We performed a prospective, non-randomized, single-center study and analyzed the clot composition in 60 consecutive patients with ischemic stroke undergoing MT. Clots were assessed by ex vivo multiparametric MRI at 9.4 T (MR microscopy), cone beam CT, and histopathology. Clot imaging was correlated with preinterventional CT and clinical data. RESULTS: MR microscopy showed red blood cell (RBC)-rich (21.7%), platelet-rich (white,38.3%) or mixed clots (40.0%) as distinct morphological entities, and MR microscopy had high accuracy of 95.4% to differentiate clots. Clot composition could be further stratified on preinterventional non-contrast head CT by quantification of the hyperdense artery sign. During MT, white clots required more passes to achieve final recanalization and were not amenable to contact aspiration compared with mixed and RBC-rich clots (maneuvers: 4.7 vs 3.1 and 1.2 passes, P<0.05 and P<0.001, respectively), whereas RBC-rich clots showed higher probability of first pass recanalization (76.9%) compared with white clots (17.4%). White clots were associated with poorer clinical outcome at discharge and 90 days after MT. CONCLUSION: Our study introduces MR microscopy to show that the hyperdense artery sign or MR relaxometry could guide interventional strategy. This could enable a personalized treatment approach to improve outcome of patients undergoing MT.

Deep-learning based detection of vessel occlusions on CT-angiography in patients with suspected acute ischemic stroke.

Swift diagnosis and treatment play a decisive role in the clinical outcome of patients with acute ischemic stroke (AIS), and computer-aided diagnosis (CAD) systems can accelerate the underlying diagnostic processes. Here, we developed an artificial neural network (ANN) which allows automated detection of abnormal vessel findings without any a-priori restrictions and in <2 minutes. Pseudo-prospective external validation was performed in consecutive patients with suspected AIS from 4 different hospitals during a 6-month timeframe and demonstrated high sensitivity (≥87%) and negative predictive value (≥93%). Benchmarking against two CE- and FDA-approved software solutions showed significantly higher performance for our ANN with improvements of 25-45% for sensitivity and 4-11% for NPV (p ≤ 0.003 each). We provide an imaging platform ( https://stroke.neuroAI-HD.org ) for online processing of medical imaging data with the developed ANN, including provisions for data crowdsourcing, which will allow continuous refinements and serve as a blueprint to build robust and generalizable AI algorithms.

Deep Learning-based Assessment of Internal Carotid Artery Anatomy to Predict Difficult Intracranial Access in Endovascular Recanalization of Acute Ischemic Stroke.

BACKGROUND: Endovascular thrombectomy (EVT) duration is an important predictor for neurological outcome. Recently it was shown that an angle of ≤ 90° of the internal carotid artery (ICA) is predictive for longer EVT duration. As manual angle measurement is not trivial and time-consuming, deep learning (DL) could help identifying difficult EVT cases in advance. METHODS: We included 379 CT angiographies (CTA) of patients who underwent EVT between January 2016 and December 2020. Manual segmentation of 121 CTAs was performed for the aortic arch, common carotid artery (CCA) and ICA. These were used to train a nnUNet. The remaining 258 CTAs were segmented using the trained nnUNet with manual verification afterwards. Angles of left and right ICAs were measured resulting in two classes: acute angle ≤ 90° and > 90°. The segmentations together with angle measurements were used to train a convolutional neural network (CNN) determining the ICA angle. The performance was evaluated using Dice scores. The classification was evaluated using AUC and accuracy. Associations of ICA angle and procedural times was explored using median and Whitney­U test. RESULTS: Median EVT duration for cases with ICA angle > 90° was 48 min and with ≤ 90° was 64 min (p = 0.001). Segmentation evaluation showed Dice scores of 0.94 for the aorta and 0.86 for CCA/ICA, respectively. Evaluation of ICA angle determination resulted in an AUC of 0.92 and accuracy of 0.85. CONCLUSION: The association between ICA angle and EVT duration could be verified and a DL-based method for semi-automatic assessment with the potential for full automation was developed. More anatomical features of interest could be examined in a similar fashion.

Location-specific ASPECTS does not improve Outcome Prediction in Large Vessel Occlusion compared to Cumulative ASPECTS.

PURPOSE: Individual regions of the Alberta Stroke Programme Early CT Score (ASPECTS) may contribute differently to the clinical symptoms in large vessel occlusion (LVO). Here, we investigated whether the predictive performance on clinical outcome can be increased by considering specific ASPECTS subregions. METHODS: A consecutive series of patients with LVO affecting the middle cerebral artery territory and subsequent endovascular treatment (EVT) between January 2015 and July 2020 was analyzed, including affected ASPECTS regions. A multivariate logistic regression was performed to assess the individual impact of ASPECTS regions on good clinical outcome (defined as modified Rankin scale after 90 days of 0-2). Machine-learning-driven logistic regression models were trained (training = 70%, testing = 30%) to predict good clinical outcome using i) cumulative ASPECTS and ii) location-specific ASPECTS, and their performance compared using deLong's test. Furthermore, additional analyses using binarized as well as linear clinical outcomes using regression and machine-learning techniques were applied to thoroughly assess the potential predictive properties of individual ASPECTS regions and their combinations. RESULTS: Of 1109 patients (77.3 years ± 11.6, 43.8% male), 419 achieved a good clinical outcome and a median NIHSS after 24 h of 12 (interquartile range, IQR 4-21). Individual ASPECTS regions showed different impact on good clinical outcome in the multivariate logistic regression, with strongest effects for insula (odds ratio, OR 0.56, 95% confidence interval, CI 0.42-0.75) and M5 (OR 0.53, 95% CI 0.29-0.97) regions. Accuracy (ACC) in predicting good clinical outcome of the test set did not differ between when considering i) cumulative ASPECTS and ii) location-specific ASPECTS (ACC = 0.619, 95% CI 0.58-0.64 vs. ACC = 0.629, 95% CI 0.60-0.65; p = 0.933). CONCLUSION: Cumulative ASPECTS assessment in LVO remains a stable and reliable predictor for clinical outcome and is not inferior to a weighted (location-specific) ASPECTS assessment.

Experimental investigation of transvenous embolization of arteriovenous malformations using different in vivo models.

BACKGROUND: Transvenous embolization (TVE) is an emerging technique for the endovascular treatment of cerebral arteriovenous malformations (AVMs). The aim of this study was to investigate two in vivo AVM models and to assess TVE techniques using these models. METHODS: Blood flow in the porcine rete mirabile (RM) was modified by either creating a carotid-jugular fistula or by placing a balloon guide catheter in the carotid artery. The RM was embolized with precipitating hydrophobic injectable liquid (PHIL) 25% via transarterial embolization (TAE; control group) and compared with TVE applying the transvenous retrograde pressure cooker technique and TVE using a Woven EndoBridge (WEB) device for flow control (n=6, respectively). The embolization extent (penetration of the RM), the number of events of reflux or embolization distal to the RM and the procedure times were assessed. RESULTS: The modified RM could be successfully used for embolization in all cases. There were no significant differences regarding the outcome parameters between the two AVM models (fistula or balloon). TVE using the pressure cooker technique led to a higher extent of embolization (median 98.8% vs 63.5%; p=0.008), a lower number of reflux or distal embolization events (p<0.001) and a shorter procedure time (p<0.001) compared with conventional TAE. TVE using a WEB device for flow control was technically feasible and achieved a moderate extent of embolization (median 83.8%). CONCLUSION: After surgical or endovascular modification, the porcine RM is a feasible in vivo AVM model for the investigation of TVE techniques. TVE using the pressure cooker technique is superior to conventional TAE in this experimental model.

Aortic Arch Variations and Supra-aortic Arterial Tortuosity in Stroke Patients Undergoing Thrombectomy : Retrospective Analysis of 1705 Cases.

PURPOSE: Unfavorable vascular anatomy can impede thrombectomy in patients with acute ischemic stroke. The aim of this study was to determine the prevalence of aortic arch types, aortic arch branching patterns and supra-aortic arterial tortuosity in stroke patients with large vessel occlusion. METHODS: Computed tomography (CT) and magnetic resonance (MR) images of all stroke patients in an institutional thrombectomy registry were retrospectively reviewed. Aortic arch types and branching patterns of all patients were determined. In patients with anterior circulation stroke, the prevalence of tortuosity (elongation, kinking or coiling) of the supra-aortic arteries of the affected side was additionally assessed. RESULTS: A total of 1705 aortic arches were evaluated. Frequency of aortic arch types I, II and III were 777 (45.6%), 585 (34.3%) and 340 (19.9%), respectively. In 1232 cases (72.3%), there was a normal branching pattern of the aortic arch. The brachiocephalic trunk and the left common carotid artery had a common origin in 258 cases (15.1%). In 209 cases (12.3%), the left common carotid artery arose from the brachiocephalic trunk. Of 1598 analyzed brachiocephalic trunks and/or common carotid arteries, 844 (52.8%) had no vessel tortuosity, 592 (37.0%) had elongation, 155 (9.7%) had kinking, and 7 (0.4%) had coiling. Of 1311 analyzed internal carotid arteries, 471 (35.9%) had no vessel tortuosity, 589 (44.9%) had elongation, 150 (11.4%) had kinking, and 101 (7.7%) had coiling. CONCLUSION: With 20%, type III aortic arches are found in a relevant proportion of stroke patients eligible for mechanical thrombectomy. Nearly half of the stroke patients present with supra-aortic arterial tortuosity, mostly arterial elongation.

Clinical value of automated volumetric quantification of early ischemic tissue changes on non-contrast CT.

BACKGROUND: Quantitative and automated volumetric evaluation of early ischemic changes on non-contrast CT (NCCT) has recently been proposed as a new tool to improve prognostic performance in patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS). We aimed to test its clinical value compared with the Alberta Stroke Program Early CT Score (ASPECTS) in a large single-institutional patient cohort. METHODS: A total of 1103 patients with AIS due to large vessel occlusion in the M1 or proximal M2 segments who underwent NCCT and EVT between January 2013 and November 2019 were retrospectively enrolled. Acute ischemic volumes (AIV) and ASPECTS were generated from the baseline NCCT through e-ASPECTS (Brainomix). Correlations were tested using Spearman's coefficient. The predictive capabilities of AIV for a favorable outcome (modified Rankin Scale score at 90 days ≤2) were tested using multivariable logistic regression as well as machine-learning models. Performance of the models was assessed using receiver operating characteristic (ROC) curves and differences were tested using DeLong's test. RESULTS: Patients with a favorable outcome had a significantly lower AIV (median 12.0 mL (IQR 5.7-21.7) vs 18.8 mL (IQR 9.4-33.9), p<0.001). AIV was highly correlated with ASPECTS (rho=0.78, p<0.001) and weakly correlated with the National Institutes of Health Stroke Scale score at baseline (rho=0.22, p<0.001), and was an independent predictor of an unfavorable clinical outcome (adjusted OR 0.97, 95% CI 0.96 to 0.98). No significant difference was found between machine-learning models using either AIV or ASPECTS or both metrics for predicting a good clinical outcome (p>0.05). CONCLUSION: AIV is an independent predictor of clinical outcome and presented a non-inferior performance compared with ASPECTS, without clear advantages for prognostic modelling.

Deep learning super-resolution magnetic resonance spectroscopic imaging of brain metabolism and mutant isocitrate dehydrogenase glioma.

Background: Magnetic resonance spectroscopic imaging (MRSI) can be used in glioma patients to map the metabolic alterations associated with IDH1,2 mutations that are central criteria for glioma diagnosis. The aim of this study was to achieve super-resolution (SR) MRSI using deep learning to image tumor metabolism in patients with mutant IDH glioma. Methods: We developed a deep learning method based on generative adversarial network (GAN) using Unet as generator network to upsample MRSI by a factor of 4. Neural networks were trained on simulated metabolic images from 75 glioma patients. The performance of deep neuronal networks was evaluated on MRSI data measured in 20 glioma patients and 10 healthy controls at 3T with a whole-brain 3D MRSI protocol optimized for detection of d-2-hydroxyglutarate (2HG). To further enhance structural details of metabolic maps we used prior information from high-resolution anatomical MR imaging. SR MRSI was compared to ground truth by Mann-Whitney U-test of peak signal-to-noise ratio (PSNR), structure similarity index measure (SSIM), feature-based similarity index measure (FSIM), and mean opinion score (MOS). Results: Deep learning SR improved PSNR by 17%, SSIM by 5%, FSIM by 7%, and MOS by 30% compared to conventional interpolation methods. In mutant IDH glioma patients proposed method provided the highest resolution for 2HG maps to clearly delineate tumor margins and tumor heterogeneity. Conclusions: Our results indicate that proposed deep learning methods are effective in enhancing spatial resolution of metabolite maps. Patient results suggest that this may have great clinical potential for image guided precision oncology therapy.

Leaving the day behind: endovascular therapy beyond 24 h in acute stroke of the anterior and posterior circulation.

Background: There is little evidence of endovascular therapy (EVT) being performed in acute ischemic stroke beyond 24 h, and that evidence is limited to anterior circulation stroke. Objective: To extend evidence of efficacy and safety of EVT after more than 24 h in both anterior and posterior circulation stroke. Methods: Local, prospectively collected registries were screened for patients with acute ischemic stroke and large-vessel occlusion who had received either EVT > 24 h after last-seen-well but <24 h after symptom recognition (EVT>24LSW) or EVT > 24 h since first (definitive) symptom recognition (EVT>24DEF). Patients treated <24 h served as a group for comparison. Favorable outcome was defined as modified Rankin scale (mRS) 0-2 or return to prestroke mRS at 3 months. Results: Between January 2014 and August 2021, N = 2347 were treated with EVT at our comprehensive stroke center, of whom n = 43 met the inclusion criteria (EVT>24LSW, n = 16, EVT>24DEF, n = 27). EVT>24LSW patients were treated at a median of 28.7 h [interquartile range (IQR) = 27.3-32.8] after last-seen-well and 7.3 h (IQR = 2.8-14.3) after symptom recognition; EVT>24DEF patients were treated 52.5 h (IQR = 26.5-94.2) after first symptoms. Favorable outcome was achieved by 23.3% (10/43) in the EVT > 24 compared with 39.4% (886/2250) in the EVT < 24 group (p = 0.04). Bleeding rates were similar across groups. Mortality was also similar [EVT > 24, 27.9% (12/43) versus EVT < 24, 25.7% (584/2264), p = 0.727; posterior circulation, EVT > 24, 41.7% (5/12) versus EVT < 24, 36.5% (92/252) p = 0.764]. Conclusion: In selected patients, EVT seems effective and safe beyond 24 h for both anterior and posterior circulation stroke.

Dynamics of cerebral perfusion and oxygenation parameters following endovascular treatment of acute ischemic stroke.

BACKGROUND: We studied the effects of endovascular treatment (EVT) and the impact of the extent of recanalization on cerebral perfusion and oxygenation parameters in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO). METHODS: Forty-seven patients with anterior LVO underwent computed tomography perfusion (CTP) before and immediately after EVT. The entire ischemic region (Tmax >6 s) was segmented before intervention, and tissue perfusion (time-to-maximum (Tmax), time-to-peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF)) and oxygenation (coefficient of variation (COV), capillary transit time heterogeneity (CTH), metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF)) parameters were quantified from the segmented area at baseline and the corresponding area immediately after intervention, as well as within the ischemic core and penumbra. The impact of the extent of recanalization (modified Treatment in Cerebral Infarction (mTICI)) on CTP parameters was assessed with the Wilcoxon test and Pearson's correlation coefficients. RESULTS: The Tmax, MTT, OEF and CTH values immediately after EVT were lower in patients with complete (as compared with incomplete) recanalization, whereas CBF and COV values were higher (P<0.05) and no differences were found in other parameters. The ischemic penumbra immediately after EVT was lower in patients with complete recanalization as compared with those with incomplete recanalization (P=0.002), whereas no difference was found for the ischemic core (P=0.12). Specifically, higher mTICI scores were associated with a greater reduction of ischemic penumbra volumes (R²=-0.48 (95% CI -0.67 to -0.22), P=0.001) but not of ischemic core volumes (P=0.098). CONCLUSIONS: Our study demonstrates that the ischemic penumbra is the key target of successful EVT in patients with AIS and largely determines its efficacy on a tissue level. Furthermore, we confirm the validity of the mTICI score as a surrogate parameter of interventional success on a tissue perfusion level.

Diagnostic value of gadolinium contrast administration for spinal cord magnetic resonance imaging in multiple sclerosis patients and correlative markers of lesion enhancement.

Background: Magnetic resonance imaging is essential for monitoring people with multiple sclerosis, but the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging is unclear. Objective: To assess the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging follow-up examinations and identify imaging markers correlating with lesion enhancement. Methods: A total of 65 multiple sclerosis patients with at least 2 spinal magnetic resonance imaging follow-up examinations were included. Spine magnetic resonance imaging was performed at 3 Tesla with a standardized protocol (sagittal and axial T2-weighted turbo spin echo and T1-weighted post-contrast sequences). T2 lesion load and enhancing lesions were assessed by two independent neuroradiologists for lesion size, localization, and T2 signal ratio (T2 signallesion/T2 signalnormal appearing spinal cord). Results: A total of 68 new spinal T2 lesions and 20 new contrast-enhancing lesions developed during follow-up. All enhancing lesions had a discernable correlate as a new T2 lesion. Lesion enhancement correlated with a higher T2 signal ratio compared to non-enhancing lesions (T2 signal ratio: 2.0 ± 0.4 vs. 1.4 ± 0.2, ****p < 0.001). Receiver operating characteristics analysis showed an optimal cutoff value of signal ratio 1.78 to predict lesion enhancement (82% sensitivity and 97% specificity). Conclusion: Gadolinium contrast administration is dispensable in follow-up spine magnetic resonance imaging if no new T2 lesions are present. Probability of enhancement correlates with the T2 signal ratio.

Deep-learning-based synthesis of post-contrast T1-weighted MRI for tumour response assessment in neuro-oncology: a multicentre, retrospective cohort study.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are widely used to enhance tissue contrast during MRI scans and play a crucial role in the management of patients with cancer. However, studies have shown gadolinium deposition in the brain after repeated GBCA administration with yet unknown clinical significance. We aimed to assess the feasibility and diagnostic value of synthetic post-contrast T1-weighted MRI generated from pre-contrast MRI sequences through deep convolutional neural networks (dCNN) for tumour response assessment in neuro-oncology. METHODS: In this multicentre, retrospective cohort study, we used MRI examinations to train and validate a dCNN for synthesising post-contrast T1-weighted sequences from pre-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery sequences. We used MRI scans with availability of these sequences from 775 patients with glioblastoma treated at Heidelberg University Hospital, Heidelberg, Germany (775 MRI examinations); 260 patients who participated in the phase 2 CORE trial (1083 MRI examinations, 59 institutions); and 505 patients who participated in the phase 3 CENTRIC trial (3147 MRI examinations, 149 institutions). Separate training runs to rank the importance of individual sequences and (for a subset) diffusion-weighted imaging were conducted. Independent testing was performed on MRI data from the phase 2 and phase 3 EORTC-26101 trial (521 patients, 1924 MRI examinations, 32 institutions). The similarity between synthetic and true contrast enhancement on post-contrast T1-weighted MRI was quantified using the structural similarity index measure (SSIM). Automated tumour segmentation and volumetric tumour response assessment based on synthetic versus true post-contrast T1-weighted sequences was performed in the EORTC-26101 trial and agreement was assessed with Kaplan-Meier plots. FINDINGS: The median SSIM score for predicting contrast enhancement on synthetic post-contrast T1-weighted sequences in the EORTC-26101 test set was 0·818 (95% CI 0·817-0·820). Segmentation of the contrast-enhancing tumour from synthetic post-contrast T1-weighted sequences yielded a median tumour volume of 6·31 cm3 (5·60 to 7·14), thereby underestimating the true tumour volume by a median of -0·48 cm3 (-0·37 to -0·76) with the concordance correlation coefficient suggesting a strong linear association between tumour volumes derived from synthetic versus true post-contrast T1-weighted sequences (0·782, 0·751-0·807, p<0·0001). Volumetric tumour response assessment in the EORTC-26101 trial showed a median time to progression of 4·2 months (95% CI 4·1-5·2) with synthetic post-contrast T1-weighted and 4·3 months (4·1-5·5) with true post-contrast T1-weighted sequences (p=0·33). The strength of the association between the time to progression as a surrogate endpoint for predicting the patients' overall survival in the EORTC-26101 cohort was similar when derived from synthetic post-contrast T1-weighted sequences (hazard ratio of 1·749, 95% CI 1·282-2·387, p=0·0004) and model C-index (0·667, 0·622-0·708) versus true post-contrast T1-weighted MRI (1·799, 95% CI 1·314-2·464, p=0·0003) and model C-index (0·673, 95% CI 0·626-0·711). INTERPRETATION: Generating synthetic post-contrast T1-weighted MRI from pre-contrast MRI using dCNN is feasible and quantification of the contrast-enhancing tumour burden from synthetic post-contrast T1-weighted MRI allows assessment of the patient's response to treatment with no significant difference by comparison with true post-contrast T1-weighted sequences with administration of GBCAs. This finding could guide the application of dCNN in radiology to potentially reduce the necessity of GBCA administration. FUNDING: Deutsche Forschungsgemeinschaft.

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

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

Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke.

BACKGROUND: Despite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance. METHODS: Patients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0-2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms. RESULTS: Overall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)). CONCLUSIONS: After complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.

Reasons for Failed Mechanical Thrombectomy in Posterior Circulation Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: To determine reasons for failed recanalization in mechanical thrombectomy (MT) of the posterior circulation. METHODS: Retrospective single center analysis of reasons for MT failure in the posterior circulation. Failed MTs were categorized according to the reason for procedure failure in failed vascular access, failed passage of the target vessel occlusion and MT failure after passing the occluded target vessel. Patient characteristics were compared between failed and successful MT. RESULTS: Patients with failed MT (30/218 patients, 13.8%) were categorized into futile vascular access (13/30, 43.3%), abortive passage of the target vessel occlusion (6/30, 20.0%) and MT failure after passing the vessel occlusion (11/30, 36.7%). In 188/218 (86.2%) successful MTs alternative vascular access, local intra-arterial (i.a.) thrombolysis and emergency stent-assisted PTA prevented 65 MT failures. Patients with failed MT showed a higher NIHSS at discharge, a higher pc-ASPECTS in follow-up imaging, a higher mRS 90 days after stroke onset and a high mortality rate of 77.0% (mRS at 90 days, median (IQR): 6 (6-6) vs. 4 (2-6) for successful MT, p-value < 0.001). Co-morbidities and stroke etiology were not different compared to sufficient recanalization with atherosclerotic disease as the leading stroke etiology in both groups. CONCLUSION: Failure of MT in posterior circulation ischemic stroke patients is associated with a high mortality rate. Reasons for MT failure are diverse with futile vascular access and MT failure after passing the vessel occlusion as the leading causes. Alternative vascular access, local i.a. thrombolysis and stent-assisted PTA can prevent MT failure.

Stereotactic Radiosurgery With Concurrent Immunotherapy in Melanoma Brain Metastases Is Feasible and Effective.

Objective: Stereotactic radiosurgery (SRS) is an established treatment for brain metastases in the management of metastasized melanoma. The increasing use of checkpoint inhibitors in melanoma therapy leads to combined treatment schemes consisting of immunotherapy and SRS that need to be evaluated regarding safety and feasibility. Methods: We retrospectively analyzed 36 patients suffering from cerebral metastasized melanoma. Between November 2011 and May 2016, altogether 66 brain metastases were treated with single-fraction SRS (18-20 Gy prescribed to the 80% isodose) in combination with a checkpoint inhibitor (ipilimumab: 82%, pembrolizumab: 14% or nivolumab: 4%), administered within 3 months before or after SRS. Toxicity was evaluated with focus on the incidence of central nervous system (CNS) radiation necrosis (CRN). Overall survival (OS), freedom from local progression (FFLP), freedom from central nervous system radiation necrosis (FFCRN), and freedom from distant intracranial progression (FFDIP) were analyzed using the Kaplan-Meier method. Results: The median follow-up was 25 months (range: 2-115 months). Two patients (6%) presented with cerebral edema CTCAE °III and another two patients (6%) presented with one-sided muscle weakness CTCAE °III after SRS. One of these four symptomatic cases correlated with an observed CRN, the other three symptomatic cases were related to local tumor progression (n = 2) or related to the performance of additional whole brain radiotherapy (WBRT). No further CTCAE °III or °IV toxicity was seen. During follow-up, seven of the growing contrast-enhanced lesions were resected, revealing two cases of CRN and five cases of local tumor progression. Altogether, the observed CRN rate of the irradiated metastases was 6-17% at the time of analysis, ranging due to the radiologically challenging differentiation between CRN and local tumor progression. The observed ranges of the 1- and 2-years FFLP rates were 82-85% and 73-80%, respectively. The median FFDIP was 6.1 months, the median OS was 22.2 months. Conclusion: In the presented cohort, the combination of SRS and checkpoint inhibitors in the management of cerebral metastasized melanoma was safe and effective. Compared to historic data on SRS only, the observed CRN rate was acceptable. To gain resilient data on the incidence of CRN after combined treatment schemes, prospective trials are needed.