Non-invasive quantification of pressure drops in stenotic intracranial vessels: using deep learning-enhanced 4D flow MRI to characterize the regional haemodynamics of the pulsing brain

Stenosis of major intracranial arteries is a significant cause of stroke, with assessment of trans-stenotic pressure drops being a key marker of functional stenosis severity. Non-invasive methods for quantifying intracranial pressure changes are hence crucial; however, the narrow and tortuous cerebrovascular network poses challenges to traditional assessment methods such as transcranial Doppler. This study investigates the use of novel deep learning-enhanced super-resolution (SR) four-dimensional (4D) flow magnetic resonance imaging (MRI) in combination with a physics-informed virtual work–energy relative pressure technique to quantify pressure drops across stenotic intracranial arteries. Performance was validated in intracranial-mimicking in vitro experiments using pulsatile flow before being transferred into an in vivo cohort of patients with intracranial atherosclerotic disease. Conversion into sub-millimetre SR imaging significantly improved the accuracy of regional relative pressure estimations in the pulsing brain arteries, mitigating biases observed at >1 mm resolution imaging, and agreeing strongly with reference catheter- based invasive measurements across both moderate and severe stenoses. The in vivo analysis also revealed a significant increase in pressure drops when converting into sub-millimetre SR data, underlining the importance of apparent image resolution in a clinical setting. The results highlight the potential of SR 4D flow MRI for non-invasive quantification of cerebrovascular pressure changes in pulsing intracranial arteries across stenotic vessel segments

Cessation and Resumption of Elective Neurointerventional Procedures during the Coronavirus Disease 2019 Pandemic and Future Pandemics

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on elective neurointerventional procedures is generally credited with helping to flatten the curve and direct scarce resources to more acutely ill patients; however, there have been reports of some delaying seeking medical care when it was in fact urgent, and other reports of patients having elective treatment delayed with the result of morbidity and mortality. Many regions have resumed elective neurointerventional procedures, only to now watch coronavirus disease 2019 positivity rates again climbing as winter of 2020 approaches. A new wave is now forecast which may have larger volumes of hospitalized coronavirus disease 2019 patients than the earlier wave(s) and may also coincide with a wave of patients hospitalized with seasonal influenza. This paper discusses relevant and practical elements of cessation and safe resumption of nonemergent neurointerventional services in the setting of a pandemic

Robust Single-view Cone-beam X-ray Pose Estimation with Neural Tuned Tomography (NeTT) and Masked Neural Radiance Fields (mNeRF)

Many tasks performed in image-guided, mini-invasive, medical procedures can be cast as pose estimation problems, where an X-ray projection is utilized to reach a target in 3D space. Expanding on recent advances in the differentiable rendering of optically reflective materials, we introduce new methods for pose estimation of radiolucent objects using X-ray projections, and we demonstrate the critical role of optimal view synthesis in performing this task. We first develop an algorithm (DiffDRR) that efficiently computes Digitally Reconstructed Radiographs (DRRs) and leverages automatic differentiation within TensorFlow. Pose estimation is performed by iterative gradient descent using a loss function that quantifies the similarity of the DRR synthesized from a randomly initialized pose and the true fluoroscopic image at the target pose. We propose two novel methods for high-fidelity view synthesis, Neural Tuned Tomography (NeTT) and masked Neural Radiance Fields (mNeRF). Both methods rely on classic Cone-Beam Computerized Tomography (CBCT); NeTT directly optimizes the CBCT densities, while the non-zero values of mNeRF are constrained by a 3D mask of the anatomic region segmented from CBCT. We demonstrate that both NeTT and mNeRF distinctly improve pose estimation within our framework. By defining a successful pose estimate to be a 3D angle error of less than 3 deg, we find that NeTT and mNeRF can achieve similar results, both with overall success rates more than 93%. However, the computational cost of NeTT is significantly lower than mNeRF in both training and pose estimation. Furthermore, we show that a NeTT trained for a single subject can generalize to synthesize high-fidelity DRRs and ensure robust pose estimations for all other subjects. Therefore, we suggest that NeTT is an attractive option for robust pose estimation using fluoroscopic projections

Automated intracranial vessel segmentation of 4D flow MRI data in patients with atherosclerotic stenosis using a convolutional neural network

Introduction Intracranial 4D flow MRI enables quantitative assessment of hemodynamics in patients with intracranial atherosclerotic disease (ICAD). However, quantitative assessments are still challenging due to the time-consuming vessel segmentation, especially in the presence of stenoses, which can often result in user variability. To improve the reproducibility and robustness as well as to accelerate data analysis, we developed an accurate, fully automated segmentation for stenosed intracranial vessels using deep learning. Methods 154 dual-VENC 4D flow MRI scans (68 ICAD patients with stenosis, 86 healthy controls) were retrospectively selected. Manual segmentations were used as ground truth for training. For automated segmentation, deep learning was performed using a 3D U-Net. 20 randomly selected cases (10 controls, 10 patients) were separated and solely used for testing. Cross-sectional areas and flow parameters were determined in the Circle of Willis (CoW) and the sinuses. Furthermore, the flow conservation error was calculated. For statistical comparisons, Dice scores (DS), Hausdorff distance (HD), average symmetrical surface distance (ASSD), Bland-Altman analyses, and interclass correlations were computed using the manual segmentations from two independent observers as reference. Finally, three stenosis cases were analyzed in more detail by comparing the 4D flow-based segmentations with segmentations from black blood vessel wall imaging (VWI). Results Training of the network took approximately 10 h and the average automated segmentation time was 2.2 ± 1.0 s. No significant differences in segmentation performance relative to two independent observers were observed. For the controls, mean DS was 0.85 ± 0.03 for the CoW and 0.86 ± 0.06 for the sinuses. Mean HD was 7.2 ± 1.5 mm (CoW) and 6.6 ± 3.7 mm (sinuses). Mean ASSD was 0.15 ± 0.04 mm (CoW) and 0.22 ± 0.17 mm (sinuses). For the patients, the mean DS was 0.85 ± 0.04 (CoW) and 0.82 ± 0.07 (sinuses), the HD was 8.4 ± 3.1 mm (CoW) and 5.7 ± 1.9 mm (sinuses) and the mean ASSD was 0.22 ± 0.10 mm (CoW) and 0.22 ± 0.11 mm (sinuses). Small bias and limits of agreement were observed in both cohorts for the flow parameters. The assessment of the cross-sectional lumen areas in stenosed vessels revealed very good agreement (ICC: 0.93) with the VWI segmentation but a consistent overestimation (bias ± LOA: 28.1 ± 13.9%). Discussion Deep learning was successfully applied for fully automated segmentation of stenosed intracranial vasculatures using 4D flow MRI data. The statistical analysis of segmentation and flow metrics demonstrated very good agreement between the CNN and manual segmentation and good performance in stenosed vessels. To further improve the performance and generalization, more ICAD segmentations as well as other intracranial vascular pathologies will be considered in the future

The professional and personal impact of the coronavirus pandemic on US neurointerventional practices: a nationwide survey

Background Little is currently known about the effects of the coronavirus (COVID-19) pandemic on neurointerventional (NI) procedural volumes or its toll on physician wellness. Methods A 37-question online survey was designed and distributed to physician members of three NI physician organizations. Results A total of 151 individual survey responses were obtained. Reduced mechanical thrombectomy procedures compared with pre-pandemic were observed with 32% reporting a greater than 50% reduction in thrombectomy volumes. In concert with most (76%) reporting at least a 25% reduction in non-mechanical thrombectomy urgent NI procedures and a nearly unanimous (96%) cessation of non-urgent elective cases, 68% of physicians reported dramatic reductions (\u3e50%) in overall NI procedural volume compared with pre-pandemic. Increased door-to- puncture times were reported by 79%. COVID-19-positive infections occurred in 1% of physician respondents: an additional 8% quarantined for suspected infection. Sixty-six percent of respondents reported increased career stress, 56% increased personal life/family stress, and 35% increased career burnout. Stress was significantly increased in physicians with COVID-positive family members (P\u3c0.05). Conclusions This is the first study designed to understand the effects of the COVID-19 pandemic on NI physician practices, case volumes, compensation, personal/family stresses, and work-related burnout. Future studies examining these factors following the resumption of elective cases and relaxing of social distancing measures will be necessary to better understand these phenomena

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations