Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2.

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.

Automated postoperative muscle assessment of hip arthroplasty patients using multimodal imaging joint segmentation.

BACKGROUND AND OBJECTIVE: In patients treated with hip arthroplasty, the muscular condition and presence of inflammatory reactions are assessed using magnetic resonance imaging (MRI). As MRI lacks contrast for bony structures, computed tomography (CT) is preferred for clinical evaluation of bone tissue and orthopaedic surgical planning. Combining the complementary information of MRI and CT could improve current clinical practice for diagnosis, monitoring and treatment planning. In particular, the different contrast of these modalities could help better quantify the presence of fatty infiltration to characterise muscular condition and assess implant failure. In this work, we combine CT and MRI for joint bone and muscle segmentation and we propose a novel Intramuscular Fat Fraction estimation method for the quantification of muscle atrophy. METHODS: Our multimodal framework is able to segment healthy and pathological musculoskeletal structures as well as implants, and develops into three steps. First, input images are pre-processed to improve the low quality of clinically acquired images and to reduce the noise associated with metal artefact. Subsequently, CT and MRI are non-linearly aligned using a novel approach which imposes rigidity constraints on bony structures to ensure realistic deformation. Finally, taking advantage of a multimodal atlas we created for this task, a multi-atlas based segmentation delineates pelvic bones, abductor muscles and implants on both modalities jointly. From the obtained segmentation, a multimodal estimation of the Intramuscular Fat Fraction can be automatically derived. RESULTS: Evaluation of the segmentation in a leave-one-out cross-validation study on 22 hip sides resulted in an average Dice score of 0.90 for skeletal and 0.84 for muscular structures. Our multimodal Intramuscular Fat Fraction was benchmarked on 27 different cases against a standard radiological score, showing stronger association than a single modality approach in a one-way ANOVA F-test analysis. CONCLUSIONS: The proposed framework represents a promising tool to support image analysis in hip arthroplasty, being robust to the presence of implants and associated image artefacts. By allowing for the automated extraction of a muscle atrophy imaging biomarker, it could quantitatively inform the decision-making process about patient's management.

Comparison of Multi-class Machine Learning Methods for the Identification of Factors Most Predictive of Prognosis in Neurobehavioral assessment of Pediatric Severe Disorder of Consciousness through LOCFAS scale.

Severe Disorders of Consciousness (DoC) are generally caused by brain trauma, anoxia or stroke, and result in conditions ranging from coma to the confused-agitated state. Prognostic decision is difficult to achieve during the first year after injury, especially in the pediatric cases. Nevertheless, prognosis crucially informs rehabilitation decision and family expectations. We compared four multi-class machine learning classification approaches for the prognostic decision in pediatric DoC. We identified domains of a neurobehavioral assessment tool, Level of Cognitive Functioning Assessment Scale, mostly contributing to decision in a cohort of 124 cases. We showed the possibility to generalize to new admitted pediatric cases, thus paving the way for real employment of machine learning classifiers as an assistive tool to prognostic decision in clinics.

Multi-contrast attenuation map synthesis for PET/MR scanners: assessment on FDG and Florbetapir PET tracers.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) scanners are expected to offer a new range of clinical applications. Attenuation correction is an essential requirement for quantification of PET data but MRI images do not directly provide a patient-specific attenuation map. Methods We further validate and extend a Computed Tomography (CT) and attenuation map (µ-map) synthesis method based on pre-acquired MRI-CT image pairs. The validation consists of comparing the CT images synthesised with the proposed method to the original CT images. PET images were acquired using two different tracers ((18)F-FDG and (18)F-florbetapir). They were then reconstructed and corrected for attenuation using the synthetic µ-maps and compared to the reference PET images corrected with the CT-based µ-maps. During the validation, we observed that the CT synthesis was inaccurate in areas such as the neck and the cerebellum, and propose a refinement to mitigate these problems, as well as an extension of the method to multi-contrast MRI data. Results With the improvements proposed, a significant enhancement in CT synthesis, which results in a reduced absolute error and a decrease in the bias when reconstructing PET images, was observed. For both tracers, on average, the absolute difference between the reference PET images and the PET images corrected with the proposed method was less than 2%, with a bias inferior to 1%. Conclusion With the proposed method, attenuation information can be accurately derived from MRI images by synthesising CT using routine anatomical sequences. MRI sequences, or combination of sequences, can be used to synthesise CT images, as long as they provide sufficient anatomical information.

Adaptive neonate brain segmentation.

Babies born prematurely are at increased risk of adverse neurodevelopmental outcomes. Recent advances suggest that measurement of brain volumes can help in defining biomarkers for neurodevelopmental outcome. These techniques rely on an accurate segmentation of the MRI data. However, due to lack of contrast, partial volume (PV) effect, the existence of both hypo- and hyper-intensities and significant natural and pathological anatomical variability, the segmentation of neonatal brain MRI is challenging. We propose a pipeline for image segmentation that uses a novel multi-model Maximum a posteriori Expectation Maximisation (MAP-EM) segmentation algorithm with a prior over both intensities and the tissue proportions, a B0 inhomogeneity correction, and a spatial homogeneity term through the use of a Markov Random Field. This robust and adaptive technique enables the segmentation of images with high anatomical disparity from a normal population. Furthermore, the proposed method implicitly models Partial Volume, mitigating the problem of neonatal white/grey matter intensity inversion. Experiments performed on a clinical cohort show expected statistically significant correlations with gestational age at birth and birthweight. Furthermore, the proposed method obtains statistically significant improvements in Dice scores when compared to the a Maximum Likelihood EM algorithm.

LoAd: a locally adaptive cortical segmentation algorithm.

Thickness measurements of the cerebral cortex can aid diagnosis and provide valuable information about the temporal evolution of diseases such as Alzheimer's, Huntington's, and schizophrenia. Methods that measure the thickness of the cerebral cortex from in-vivo magnetic resonance (MR) images rely on an accurate segmentation of the MR data. However, segmenting the cortex in a robust and accurate way still poses a challenge due to the presence of noise, intensity non-uniformity, partial volume effects, the limited resolution of MRI and the highly convoluted shape of the cortical folds. Beginning with a well-established probabilistic segmentation model with anatomical tissue priors, we propose three post-processing refinements: a novel modification of the prior information to reduce segmentation bias; introduction of explicit partial volume classes; and a locally varying MRF-based model for enhancement of sulci and gyri. Experiments performed on a new digital phantom, on BrainWeb data and on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) show statistically significant improvements in Dice scores and PV estimation (p<10(-3)) and also increased thickness estimation accuracy when compared to three well established techniques.