Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke.

BACKGROUND: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction. METHODS: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes. RESULTS: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P=0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P=0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P=0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion. CONCLUSIONS: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

PSEN1/SLC20A2 double mutation causes early-onset Alzheimer's disease and primary familial brain calcification co-morbidity.

Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF ß-amyloid parameters and FBB-PET suggested cortical ß-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.

Myelofibrosis progression grading based on type I and type III collagen and fibrillin 1 expression boosted by whole slide image analysis.

AIMS: The progression of primary myelofibrosis is characterised by ongoing extracellular matrix deposition graded based on 'reticulin' and 'collagen' fibrosis, as revealed by Gomori's silver impregnation. Here we studied the expression of the major extracellular matrix proteins of fibrosis in relation to diagnostic silver grading supported by image analysis. METHODS AND RESULTS: By using automated immunohistochemistry, in this study we demonstrate that the expression of both types I and III collagens and fibrillin 1 by bone marrow stromal cells can reveal the extracellular matrix scaffolding in line with myelofibrosis progression as classified by silver grading. 'Reticulin' fibrosis indicated by type III collagen expression and 'collagen' fibrosis featured by type I collagen expression were parallel, rather than sequential, events. This is line with the proposed role of type III collagen in regulating type I collagen fibrillogenesis. The uniformly strong fibrillin 1 immune signals offered the best inter-rater agreements and the highest statistical correlations with silver grading of the three markers, which was robustly confirmed by automated whole slide digital image analysis using a machine learning-based algorithm. The progressive up-regulation of fibrillin 1 during myelofibrosis may result from a negative feedback loop as fibrillin microfibrils sequester TGF-ß, the major promoter of fibrosis. This can also reduce TGF-ß-induced RANKL levels, which would stimulate osteoclastogenesis and thus can support osteosclerosis in advanced myelofibrosis. CONCLUSIONS: Through the in-situ detection of these extracellular matrix proteins, our results verify the molecular pathobiology of fibrosis during myelofibrosis progression. In particular, fibrillin 1 immunohistochemistry, with or without image analysis, can complement diagnostic silver grading at decent cell morphology.

Transfer learning for medical image classification: a literature review.

BACKGROUND: Transfer learning (TL) with convolutional neural networks aims to improve performances on a new task by leveraging the knowledge of similar tasks learned in advance. It has made a major contribution to medical image analysis as it overcomes the data scarcity problem as well as it saves time and hardware resources. However, transfer learning has been arbitrarily configured in the majority of studies. This review paper attempts to provide guidance for selecting a model and TL approaches for the medical image classification task. METHODS: 425 peer-reviewed articles were retrieved from two databases, PubMed and Web of Science, published in English, up until December 31, 2020. Articles were assessed by two independent reviewers, with the aid of a third reviewer in the case of discrepancies. We followed the PRISMA guidelines for the paper selection and 121 studies were regarded as eligible for the scope of this review. We investigated articles focused on selecting backbone models and TL approaches including feature extractor, feature extractor hybrid, fine-tuning and fine-tuning from scratch. RESULTS: The majority of studies (n = 57) empirically evaluated multiple models followed by deep models (n = 33) and shallow (n = 24) models. Inception, one of the deep models, was the most employed in literature (n = 26). With respect to the TL, the majority of studies (n = 46) empirically benchmarked multiple approaches to identify the optimal configuration. The rest of the studies applied only a single approach for which feature extractor (n = 38) and fine-tuning from scratch (n = 27) were the two most favored approaches. Only a few studies applied feature extractor hybrid (n = 7) and fine-tuning (n = 3) with pretrained models. CONCLUSION: The investigated studies demonstrated the efficacy of transfer learning despite the data scarcity. We encourage data scientists and practitioners to use deep models (e.g. ResNet or Inception) as feature extractors, which can save computational costs and time without degrading the predictive power.

Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage.

Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort. Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders. Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1­3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38­9.42], P=0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07­0.89], P=0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06­0.78], P=0.020) were significant protective factors against the occurrence of SICH. More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect.

BACKGROUND AND PURPOSE: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. METHODS: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. RESULTS: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0-10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7-7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8-5.6]). CONCLUSIONS: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters.

BACKGROUND: Multiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults. METHODS: We evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20-88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile. RESULTS: Age was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond. CONCLUSION: SF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range. TRIAL REGISTRATION NUMBER: NCT04099225.

Prospective Feasibility Study of Single-Shot Antibiotic Prophylaxis in Transrectal Focal Ablation of Prostate Cancer.

INTRODUCTION: Urinary tract infections (UTI) represent the most frequent complications after transrectal focal ablation of prostate cancer. Single-shot antibiotic prophylaxis for prevention has not yet been described. METHODS: In this cohort study of patients who received a high-intensity focused ultrasound (HIFU) ablation of prostate cancer within a registered prospective single-arm trial, we analyzed posttreatment UTI (≤30 days after HIFU) related to perioperative antibiotic management in an exploratory analysis: single-shot prophylaxis or targeted treatment for bacteriuria. Potential risk factors associated with UTI were evaluated by uni- and multivariate regression analyses. RESULTS: In total, 55 patients were eligible for analysis. Of these, 76.4% received antibiotic single-shot prophylaxis. UTI occurred in 10.7% of all patients, 5.4% developed fever, 3.6% required hospitalization. An antibiotic single-shot prophylaxis helped to protect 90.5% of men from infectious complications. Estimated effects indicate that a longer posttreatment catheterization (OR 3.38, 95% CI 0.47-27.08) and larger ablation volume (OR 4.85, 95% CI 0.61-107.49) might be associated with the highest risk for UTI after treatment. CONCLUSION: Single-shot antibiotic prophylaxis compared to a targeted antibiotic treatment showed a similar effectivity to prevent patients from infectious complications and should be considered as an element of antibiotic stewardship. Further research on risk factors and antibiotic strategies is required.

Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.

Contrast-enhanced fat-suppressed FLAIR for the characterization of leptomeningeal inflammation in optic neuritis.

BACKGROUND: Leptomeningeal contrast enhancement on fluid-attenuated inversion recovery (FLAIR) images has been reported in patients with multiple sclerosis and interpreted as a biomarker of inflammation. In this study, we sought to evaluate this phenomenon in patients with optic neuritis (ON). METHODS: A total of 42 patients with suspected ON were included in this prospective study and underwent a dedicated study magnetic resonance imaging (MRI) protocol including native and contrast-enhanced fat-suppressed thin-section axial and coronal FLAIR images on an 1.5 T magnetic resonance (MR) system. RESULTS: After diagnostic workup, 34 patients with final diagnosis of ON were analyzed in detail. On contrast-enhanced fat-suppressed FLAIR images, 25 (73.5%) patients with ON demonstrated perioptic leptomeningeal enhancement, and in 3 (8.8%) patients, this was even the only pathological MRI finding. In comparison, patients with perioptic leptomeningeal enhancement on contrast-enhanced fat-suppressed FLAIR images had a higher prevalence of additional hyperintense brain lesions ( p = 0.022) as well as cerebrospinal fluid (CSF)-specific oligoclonal bands ( p = 0.013) than patients without. CONCLUSION: Perioptic leptomeningeal contrast enhancement on fat-suppressed FLAIR images is a novel marker in ON and possibly reflects a leptomeningeal inflammatory process preceding or accompanying ON. Thin-section contrast-enhanced fat-suppressed FLAIR images might be a useful addition in MRI protocols for patients with suspected ON.

Incidence, Locations, and Longitudinal Course of Cerebral Microbleeds in European Moyamoya.

BACKGROUND AND PURPOSE: Cerebral microbleeds (cMBs) have previously been linked with especially high incidence in Asian patients with moyamoya together with high tendency to bleed. This, presumably, is characteristic of patients with moyamoya. Herein, we, therefore, investigate retrospectively the frequency, location, and longitudinal course of cMBs in a large German cohort. METHODS: We included all patients with moyamoya who underwent standard magnetic resonance imaging, including T2*-weighted images, in our department between 1998 and 2015. Two independent readers evaluated magnetic resonance imaging scans to determine the occurrence of cMBs according to the Brain Observer Microbleed Scale. Demographics, initial symptoms leading to hospitalization, and associated diseases were obtained by chart review. RESULTS: Overall, there was a total of 242 T2* studies of 101 included moyamoya patients available with a strong female predominance (69.3%). Eight patients (7.9%) were ≤18 years of age. We detected 25 cMBs within 13 patients (12.9%). One patient <18 of age was presented with a cMB; 2 of 3 patients with an intracranial hemorrhage as initial event demonstrated cMB(s). In 72 of 101 cases, there were 1719 person months of follow-up, with 3 adult patients showing 3 de novo cMBs in the course. The majority of cMBs (64.0%) were located at the cortex/gray-white junction. CONCLUSIONS: Although the frequency of cMBs herein is much higher than the expected age-specific incidence, it is still much lower compared with previous reports on cMBs in moyamoya patients of Asian descent. These results might reflect another ethnic-specific difference in patients diagnosed with moyamoya.

In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging.

Small animal imaging is of increasing relevance in biomedical research. Studies systematically assessing the diagnostic accuracy of contrast-enhanced in vivo micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/γc(-/-) mice (n = 27) underwent intracerebral implantation of 2.5 × 10(6) GFP-Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI) to detect tumor growth and afterwards repeated contrast-enhanced (300 µl Iomeprol i.v.) micro-CT imaging (80 kV, 75 µAs, 360° rotation, 1,000 projections, 33 s scan time, resolution 40 × 40 × 53 µm, 0.5 Gy/scan). Presence of tumors, tumor diameter and tumor volume in micro-CT were rated by two independent readers. Results were compared with histological analyses. Six mice with tumors confirmed by micro-CT received fractionated irradiation (3 × 5 Gy every other day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor volume was 30 ± 33 mm(3), and the smallest detectable tumor measured 360 × 620 µm. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21 after tumor implantation had a sensitivity and specificity of 0.90 and 1.0, respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro-CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor growth in live mice is feasible at high sensitivity levels and with excellent inter-rater agreement and allows visualization of radiation effects.

Endovascular Thrombectomy for Large Ischemic Strokes with ASPECTS 0-2: a Meta-analysis of Randomized Controlled Trials.

PURPOSE: Randomized controlled trials (RCTs) demonstrated a treatment effect of endovascular thrombectomy in acute ischemic stroke with large infarct, commonly defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. However, data on endovascular thrombectomy in patients with very low ASPECTS of 0-2 remain scarce. METHODS: We conducted a systematic review and meta-analysis of RCTs comparing endovascular thrombectomy versus medical treatment alone in acute ischemic anterior circulation stroke with very large infarct, defined as ASPECTS of 0-2. The primary outcome was the shift toward better functional outcomes on the 90-day modified Rankin Scale (mRS). Random effects meta-analysis was performed using the generic inverse variance method. RESULTS: Literature research identified four RCTs which evaluated the treatment effect of endovascular thrombectomy for large infarcts and provided a subgroup analysis of the mRS shift in patients with ASPECTS of 0-2. The pooled analysis showed a significant shift toward better 90-day mRS scores in favor of endovascular thrombectomy (pooled odds ratio, 1.62, 95% confidence interval, 1.29-2.04, P < 0.001). CONCLUSION: This meta-analysis suggests a treatment effect of endovascular thrombectomy in specific patients with very low ASPECTS of 0-2, challenging the use of ASPECTS for treatment selection in acute ischemic stroke due to large vessel occlusion. An individual patient meta-analysis of RCTs would strengthen evidence in the treatment of patients with ASPECTS of 0-2.

Early stopping versus continued retrievals after failed recanalization: associated factors and implications for outcome.

BACKGROUND: Successful recanalization defined as modified Thrombolysis in Cerebral Infarction Score (mTICI) ≥2b is not achieved in 15%-20% of patients with acute ischemic stroke. This study aims to identify patient-specific factors associated with early stopping without successful recanalization. We hypothesized that the probability of the decision for early stopping during mechanical thrombectomy (MT) is higher in patients with an unfavorable prognosis. METHODS: All patients enrolled in the German Stroke Registry (GSR) between June 2015 and December 2021 were screened. Inclusion criteria were stroke in the anterior circulation and availability of relevant clinical data. For each retrieval attempt 1-3, patients with stopping and failed reperfusion (mTICI <2b) were compared with all patients with continued retrieval attempts using descriptive statistics and multivariable logistic regression. RESULTS: Our study included 2977 patients, 350 (12%) of which had early stopping. Higher pre-stroke Modified Rankin Scale (mRS) score (adjusted odds ratio (aOR) =1.20 (95% confidence interval (CI): 1.09; 1.32), P<0.001), higher age (aOR=1.01 (1.00; 1.02), P=0.017) and distal occlusions (aOR=1.93 (1.50; 2.47), P<0.001) as well as intraprocedural dissections/perforations (aOR=4.61 (2.95; 7.20), P<0.001) and extravasation (aOR=2.43 (1.55;3.82), P<0.001) were associated with early stopping. In patients with unsuccessful recanalization (n=622), the number of retrieval attempts (aOR=1.05 (0.94; 1.18), p=0.405) was not associated with unfavorable outcomes (90d-mRS>3). CONCLUSION: The probability of early stopping was higher in patients with clinical conditions associated with: a) Favorable prognosis and assumed lower impact of recanalization success on functional status, such as distal occlusions; and b) Unfavorable prognosis, such as higher age and reduced pre-stroke functional status. Adverse events during the procedure increased the probability of early stopping. The number of recanalization attempts did not increase the risk of unfavorable outcome for patients with persistent occlusion, supporting the decision for continuation of retrieval attempts.

Prediction of tissue outcome in acute ischemic stroke based on single-phase CT angiography at admission.

Introduction: In acute ischemic stroke, prediction of the tissue outcome after reperfusion can be used to identify patients that might benefit from mechanical thrombectomy (MT). The aim of this work was to develop a deep learning model that can predict the follow-up infarct location and extent exclusively based on acute single-phase computed tomography angiography (CTA) datasets. In comparison to CT perfusion (CTP), CTA imaging is more widely available, less prone to artifacts, and the established standard of care in acute stroke imaging protocols. Furthermore, recent RCTs have shown that also patients with large established infarctions benefit from MT, which might not have been selected for MT based on CTP core/penumbra mismatch analysis. Methods: All patients with acute large vessel occlusion of the anterior circulation treated at our institution between 12/2015 and 12/2020 were screened (N = 404) and 238 patients undergoing MT with successful reperfusion were included for final analysis. Ground truth infarct lesions were segmented on 24 h follow-up CT scans. Pre-processed CTA images were used as input for a U-Net-based convolutional neural network trained for lesion prediction, enhanced with a spatial and channel-wise squeeze-and-excitation block. Post-processing was applied to remove small predicted lesion components. The model was evaluated using a 5-fold cross-validation and a separate test set with Dice similarity coefficient (DSC) as the primary metric and average volume error as the secondary metric. Results: The mean ± standard deviation test set DSC over all folds after post-processing was 0.35 ± 0.2 and the mean test set average volume error was 11.5 mL. The performance was relatively uniform across models with the best model according to the DSC achieved a score of 0.37 ± 0.2 after post-processing and the best model in terms of average volume error yielded 3.9 mL. Conclusion: 24 h follow-up infarct prediction using acute CTA imaging exclusively is feasible with DSC measures comparable to results of CTP-based algorithms reported in other studies. The proposed method might pave the way to a wider acceptance, feasibility, and applicability of follow-up infarct prediction based on artificial intelligence.

Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage.

Objective: Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. Methods: Patients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed. Results: Of 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p < 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28-4.72, p < 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78-3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37-1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI. Conclusion: Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

Lightweight Visual Transformers Outperform Convolutional Neural Networks for Gram-Stained Image Classification: An Empirical Study.

We aimed to automate Gram-stain analysis to speed up the detection of bacterial strains in patients suffering from infections. We performed comparative analyses of visual transformers (VT) using various configurations including model size (small vs. large), training epochs (1 vs. 100), and quantization schemes (tensor- or channel-wise) using float32 or int8 on publicly available (DIBaS, n = 660) and locally compiled (n = 8500) datasets. Six VT models (BEiT, DeiT, MobileViT, PoolFormer, Swin and ViT) were evaluated and compared to two convolutional neural networks (CNN), ResNet and ConvNeXT. The overall overview of performances including accuracy, inference time and model size was also visualized. Frames per second (FPS) of small models consistently surpassed their large counterparts by a factor of 1-2×. DeiT small was the fastest VT in int8 configuration (6.0 FPS). In conclusion, VTs consistently outperformed CNNs for Gram-stain classification in most settings even on smaller datasets.

Individual glioblastoma cells harbor both proliferative and invasive capabilities during tumor progression.

BACKGROUND: Glioblastomas are characterized by aggressive and infiltrative growth, and by striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation and invasion are interrelated, or rather distinct features of different cell populations. METHODS: Tumor cell invasion and proliferation were longitudinally determined in real-time using 3D in vivo 2-photon laser scanning microscopy over weeks. Glioblastoma cells expressed fluorescent markers that permitted the identification of their mitotic history or their cycling versus non-cycling cell state. RESULTS: Live reporter systems were established that allowed us to dynamically determine the invasive behavior, and previous or actual proliferation of distinct glioblastoma cells, in different tumor regions and disease stages over time. Particularly invasive tumor cells that migrated far away from the main tumor mass, when followed over weeks, had a history of marked proliferation and maintained their proliferative capacity during brain colonization. Infiltrating cells showed fewer connections to the multicellular tumor cell network, a typical feature of gliomas. Once tumor cells colonized a new brain region, their phenotype progressively transitioned into tumor microtube-rich, interconnected, slower-cycling glioblastoma cells. Analysis of resected human glioblastomas confirmed a higher proliferative potential of tumor cells from the invasion zone. CONCLUSIONS: The detection of glioblastoma cells that harbor both particularly high proliferative and invasive capabilities during brain tumor progression provides valuable insights into the interrelatedness of proliferation and migration-2 central traits of malignancy in glioma. This contributes to our understanding of how the brain is efficiently colonized in this disease.

Rapid Convolutional Neural Networks for Gram-Stained Image Classification at Inference Time on Mobile Devices: Empirical Study from Transfer Learning to Optimization.

Despite the emergence of mobile health and the success of deep learning (DL), deploying production-ready DL models to resource-limited devices remains challenging. Especially, during inference time, the speed of DL models becomes relevant. We aimed to accelerate inference time for Gram-stained analysis, which is a tedious and manual task involving microorganism detection on whole slide images. Three DL models were optimized in three steps: transfer learning, pruning and quantization and then evaluated on two Android smartphones. Most convolutional layers (≥80%) had to be retrained for adaptation to the Gram-stained classification task. The combination of pruning and quantization demonstrated its utility to reduce the model size and inference time without compromising model quality. Pruning mainly contributed to model size reduction by 15×, while quantization reduced inference time by 3× and decreased model size by 4×. The combination of two reduced the baseline model by an overall factor of 46×. Optimized models were smaller than 6 MB and were able to process one image in <0.6 s on a Galaxy S10. Our findings demonstrate that methods for model compression are highly relevant for the successful deployment of DL solutions to resource-limited devices.