Analysis of shape and spatial interaction of synaptic vesicles using data from focused ion beam scanning electron microscopy (FIB-SEM)

The spatial interactions of synaptic vesicles in synapses were assessed after a detailed characterization of size, shape, and orientation of the synaptic vesicles. We hypothesized that shape and orientation of the synaptic vesicles are influenced by their movement towards the active zone causing deviations from spherical shape and systematic trends in their orientation.We studied three-dimensional representations of synapses obtained by manual annotation of focused ion beam scanning electron microscopy (FIB-SEM) images of male mouse brain. The configurations of synaptic vesicles were regarded as marked point patterns, where the points are the centers of the vesicles, and the mark of a vesicle is given by its size, shape, and orientation characteristics. Statistics for marked point processes were employed to study spatial interactions between vesicles.We found that the synaptic vesicles in excitatory synapses appeared to be of oblate ellipsoid shape and in inhibitory synapses appeared to be of cigar ellipsoid shape, and followed a systematic pattern regarding their orientation towards the active zone. Moreover, there was strong evidence of spatial alignment in the orientations of pairs of synaptic vesicles, and of repulsion between them, beyond that caused by their physical extent

CT Perfusion is All We Need: 4D CNN Segmentation of Penumbra and Core in Patient With Suspected Ischemic Stroke

Precise and fast prediction methods for ischemic areas comprised of dead tissue, core, and salvageable tissue, penumbra, in acute ischemic stroke (AIS) patients are of significant clinical interest. They play an essential role in improving diagnosis and treatment planning. Computed Tomography (CT) scan is one of the primary modalities for early assessment in patients with suspected AIS. CT Perfusion (CTP) is often used as a primary assessment to determine stroke location, severity, and volume of ischemic lesions. Current automatic segmentation methods for CTP mostly use already processed 3D parametric maps conventionally used for clinical interpretation by radiologists as input. Alternatively, the raw CTP data is used on a slice-by-slice basis as 2D+time input, where the spatial information over the volume is ignored. In addition, these methods are only interested in segmenting core regions, while predicting penumbra can be essential for treatment planning. This paper investigates different methods to utilize the entire 4D CTP as input to fully exploit the spatio-temporal information, leading us to propose a novel 4D convolution layer. Our comprehensive experiments on a local dataset of 152 patients divided into three groups show that our proposed models generate more precise results than other methods explored. Adopting the proposed 4D mJ-Net, a Dice Coefficient of 0.53 and 0.23 is achieved for segmenting penumbra and core areas, respectively. The code is available on https://github.com/Biomedical-Data-Analysis-Laboratory/4D-mJ-Net.git

Multi-input segmentation of damaged brain in acute ischemic stroke patients using slow fusion with skip connection

Time is a fundamental factor during stroke treatments. A fast, automatic approach that segments the ischemic regions helps treatment decisions. In clinical use today, a set of color-coded parametric maps generated from computed tomography perfusion (CTP) images are investigated manually to decide a treatment plan. We propose an automatic method based on a neural network using a set of parametric maps to segment the two ischemic regions (core and penumbra) in patients affected by acute ischemic stroke. Our model is based on a convolution-deconvolution bottleneck structure with multi-input and slow fusion. A loss function based on the focal Tversky index addresses the data imbalance issue. The proposed architecture demonstrates effective performance and results comparable to the ground truth annotated by neuroradiologists. A Dice coefficient of 0.81 for penumbra and 0.52 for core over the large vessel occlusion test set is achieved. The full implementation is available at: https://git.io/JtFGb

Multi-input segmentation of damaged brain in acute ischemic stroke patients using slow fusion with skip connection

Time is a fundamental factor during stroke treatments. A fast, automatic approach that segmentsthe ischemic regions helps treatment decisions. In clinical use today, a set of color-coded parametric maps generated from computed tomography perfusion (CTP) images are investigated manually to decide a treatment plan. We propose an automatic method based on a neural network using a set of parametric maps to segment the two ischemic regions (core and penumbra) in patients affected by acute ischemic stroke. Our model is based on a convolution-deconvolution bottleneck structure with multi-input and slow fusion. A loss function based on the focal Tversky index addresses the data imbalance issue. The proposed architecture demonstrates effective performance and results comparable to the ground truth annotated by neuroradiologists. A Dice coefficient of 0.81 for penumbra and 0.52 for core over the large vessel occlusion test set is achieved. The full implementation is available at: https://git.io/JtFGb.publishedVersio

Automatic Estimation of Coronary Blood Flow Velocity Step 1 for Developing a Tool to Diagnose Patients With Micro-Vascular Angina Pectoris

Aim: Our aim was to automatically estimate the blood velocity in coronary arteries using cine X-ray angiographic sequence. Estimating the coronary blood velocity is a key approach in investigating patients with angina pectoris and no significant coronary artery disease. Blood velocity estimation is central in assessing coronary flow reserve. Methods and Results: A multi-step automatic method for blood flow velocity estimation based on the information extracted solely from the cine X-ray coronary angiography sequence obtained by invasive selective coronary catheterization was developed. The method includes (1) an iterative process of segmenting coronary arteries modeling and removing the heart motion using a non-rigid registration, (2) measuring the area of the segmented arteries in each frame, (3) fitting the measured sequence of areas with a 7◦ polynomial to find start and stop time of dye propagation, and (4) estimating the blood flow velocity based on the time of the dye propagation and the length of the artery-tree. To evaluate the method, coronary angiography recordings from 21 patients with no obstructive coronary artery disease were used. In addition, coronary flow velocity was measured in the same patients using a modified transthoracic Doppler assessment of the left anterior descending artery. We found a moderate but statistically significant correlation between flow velocity assessed by trans thoracic Doppler and the proposed method applying both Spearman and Pearson tests. Conclusion: Measures of coronary flow velocity using a novel fully automatic method that utilizes the information from the X-ray coronary angiographic sequence were statistically significantly correlated to measurements obtained with transthoracic Doppler recordings.publishedVersio

Self-Supervised Few-Shot Learning for Ischemic Stroke Lesion Segmentation

Precise ischemic lesion segmentation plays an essential role in improving diagnosis and treatment planning for ischemic stroke, one of the prevalent diseases with the highest mortality rate. While numerous deep neural network approaches have recently been proposed to tackle this problem, these methods require large amounts of annotated regions during training, which can be impractical in the medical domain where annotated data is scarce. As a remedy, we present a prototypical few-shot segmentation approach for ischemic lesion segmentation using only one annotated sample during training. The proposed approach leverages a novel self-supervised training mechanism that is tailored to the task of ischemic stroke lesion segmentation by exploiting color-coded parametric maps generated from Computed Tomography Perfusion scans. We illustrate the benefits of our proposed training mechanism, leading to considerable improvements in performance in the few-shot setting. Given a single annotated patient, an average Dice score of 0.58 is achieved for the segmentation of ischemic lesions

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions