Image guidance and inter-fractional anatomical variation in paediatric abdominal radiotherapy

OBJECTIVES: To identify variables predicting inter fractional anatomical variationsmeasured with cone-beam CT (CBCT) throughout abdominal paediatric radiotherapy, and to assess the potential of surface-guided radiotherapy (SGRT) to monitor these changes. METHODS: Metrics of variation in gastrointestinal (GI) gas volume andseparation of the body contour and abdominal wallwere calculated from 21 planning CTs and 77 weekly CBCTs for 21 abdominal neuroblastoma patients (median 4y, range: 2 -19y). Age, sex, feeding tubes, and general anaesthesia (GA) were explored as predictive variables for anatomical variation. Furthermore,GI gas variationwas correlated with changes in body and abdominal wall separation, as well as simulated SGRT metrics of translational and rotationalcorrections between CT/CBCT. RESULTS: GI gas volumes varied 74 ± 54 ml across all scans, while body and abdominal wall separationvaried 2.0 ± 0.7 mm and4.1±1.5mmfrom planning, respectively. Patients < 3.5y (p = 0.04) and treated under GA (p < 0.01) experienced greater GI gas variation; GA was the strongest predictor in multivariate analysis (p < 0.01). Absence of feeding tubes was linked to greater body contour variation (p = 0.03). GI gas variation correlated with body (R = 0.53) and abdominal wall (R = 0.63) changes. The strongest correlations with SGRT metrics were found for anteroposterior translation (R = 0.65) androtation of the left-right axis (R = -0.36). CONCLUSIONS: Young age, GA, and absence of feeding tubes were linked to stronger inter fractional anatomical variation and are likely indicative of patients benefiting from adaptive/robust planning pathways.Our data suggests a role for SGRT toinformthe need for CBCT at each treatment fractionin this patient group. ADVANCES IN KNOWLEDGE: This is the first study to suggest the potential role of SGRT for the management of internal inter fractional anatomical variation in paediatric abdominal radiotherapy

Developing a framework for CBCT-to-CT synthesis in paediatric abdominal radiotherapy

We proposed a CBCT-to-CT synthesis framework tailored for paediatric abdominal patients. Our approach was based on the cycle-consistent generative adversarial network (cycleGAN) modified to preserve structural consistency. To adjust for differences in field-of-view and body size from different patient groups, our training data was spatially co-registered to a common field-of-view and normalised to a fixed size. The proposed framework showed improvements in generating synthetic CTs from CBCTs compared to the original implementation of cycleGAN without field-of-view adjustments and structural consistency constrain

Deep learning based synthetic CT from cone beam CT generation for abdominal paediatric radiotherapy

Objective: Adaptive radiotherapy workflows require images with the quality of computed tomography (CT) for re-calculation and re-optimisation of radiation doses. In this work we aim to improve quality of cone beam CT (CBCT) images for dose calculation using deep learning. / Approach: We propose a novel framework for CBCT-to-CT synthesis using cycle-consistent Generative 10 Adversarial Networks (cycleGANs). The framework was tailored for paediatric abdominal patients, a challenging application due to the inter-fractional variability in bowel filling and smaller patient numbers. We introduced the concept of global residuals only learning to the networks and modified the cycleGAN loss function to explicitly promote structural consistency between source and synthetic images. Finally, to compensate for the anatomical variability and address the difficulties in collecting large datasets in the 15 paediatric population, we applied a smart 2D slice selection based on the common field-of-view across the dataset (abdomen). This acted as a weakly paired data approach that allowed us to take advantage of scans from patients treated for a variety of malignancies (thoracic-abdominal-pelvic) for training purposes. We first optimised the proposed framework and benchmarked its performance on a development dataset. Later, a comprehensive quantitative evaluation was performed on an unseen 20 dataset, which included calculating global image similarity metrics, segmentation-based measures and proton therapy-specific metrics. / Main results: We found improved performance, compared to a baseline implementation, on imagesimilarity metrics such as Mean Absolute Error calculated for a matched virtual CT (55.0±16.6 proposed vs 58.9±16.8 baseline). There was also a higher level of structural agreement for gastrointestinal gas 25 between source and synthetic images measured through dice similarity overlap (0.872±0.053 proposed vs 0.846±0.052 baseline). Differences found in water-equivalent thickness metrics were also smaller for our method (3.3±2.4% proposed vs 3.7±2.8% baseline). / Significance: Our findings indicate that our innovations to the cycleGAN framework improved the quality and structure consistency of the synthetic CTs generated

The underutilisation of dual antiplatelet therapy in acute coronary syndrome

Background Despite guideline recommendation of dual antiplatelet therapy (DAPT) in treating ACS, DAPT is underutilized. Our objective was to determine independent predictors of DAPT non-prescription in ACS and describe pattern of DAPT prescription over time. Methods Patients presenting to 41 Australian hospitals with an ACS diagnosis between 2009 and 2016 were stratified according to discharge prescription with DAPT and single antiplatelet therapy (SAPT) or no antiplatelet therapy. Multiple stepwise logistic regression, accounting for within hospital clustering, was used to determine the independent predictors of DAPT non-prescription, defined as discharge with SAPT alone or no antiplatelet agent. Results 8939 patients survived to discharge with an ACS diagnosis. Of these, 6294 (70.4%) patients were discharged on DAPT, 2154 (24.1%) on SAPT and 491 (5.5%) on no antiplatelet agent. Independent predictors of DAPT non-prescription in the overall cohort were: in-hospital CABG (OR 0.09, 95%CI 0.05–0.14), discharge with warfarin (0.10 (0.07–0.14)), in hospital major bleeding (0.48 (0.34–0.67), diagnosis of unstable angina (0.35, (0.27–0.45)), non-ST-elevation myocardial infarction (0.67 (0.57–0.78)) [both vs. ST-segment elevation myocardial infarction], in hospital atrial arrhythmia (0.72 (0.60–0.86)), history of hypertension (0.83 (0.73–0.94)) and GRACE high risk (0.83 (0.71–0.98)). There was an increase in prescription of DAPT and a shift towards ticagrelor over clopidogrel for ACS from 2013 to 2016 (p\ua

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The structural connectome in traumatic brain injury: A meta-analysis of graph metrics

Although recent structural connectivity studies of traumatic brain injury (TBI) have used graph theory to evaluate alterations in global integration and functional segregation, pooled analysis is needed to examine the robust patterns of change in graph metrics across studies. Following a systematic search, 15 studies met the inclusion criteria for review. Of these, ten studies were included in a random-effects meta-analysis of global graph metrics, and subgroup analyses examined the confounding effects of severity and time since injury. The meta-analysis revealed significantly higher values of normalised clustering coefficient (gö=ö1.445, CI=[0.512, 2.378], pö=ö0.002) and longer characteristic path length (gö=ö0.514, CI=[0.190, 0.838], pö=ö0.002) in TBI patients compared with healthy controls. Our findings suggest that the TBI structural network has shifted away from the balanced small-world network towards a regular lattice. Therefore, these graph metrics may be useful markers of neurocognitive dysfunction in TBI. We conclude that the pattern of change revealed by our analysis should be used to guide hypothesis-driven research into the role of graph metrics as diagnostic and prognostic biomarkers

B-type natriuretic peptide limits infarct size in rat isolated heart via KATP channel opening

B-type natriuretic peptide (BNP) has been reported to be released from the myocardium during ischemia. We hypothesized that BNP mediates cardioprotection during ischemia-reperfusion and examined whether exogenous BNP limits myocardial infarction and the potential role of ATP-sensitive potassium (KATP) channel opening. Langendorff-perfused rat hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. The control infarct-to-risk ratio was 44.8 ± 4.4% (means ± SE). BNP perfused 10 min before ischemia limited infarct size in a concentration-dependent manner, with maximal protection observed at 10−8 M (infarct-to-risk ratio: 20.1 ± 5.2%,P < 0.01 vs. control), associated with a 2.5-fold elevation of myocardial cGMP above the control value. To examine the role of KATP channel opening, glibenclamide (10−6 M), 5-hydroxydecanoate (5-HD; 10−4 M), or HMR-1098 (10−5 M) was coperfused with BNP (10−8 M). Protection afforded by BNP was abolished by glibenclamide or 5-HD but not by HMR-1098, suggesting the involvement of putative mitochondrial but not sarcolemmal KATP channel opening. We conclude that natriuretic peptide/cGMP/KATPchannel signaling may constitute an important injury-limiting mechanism in myocardium