Self-supervised Representation Learning for Ultrasound Video

Recent advances in deep learning have achieved promising performance for medical image analysis, while in most cases ground-truth annotations from human experts are necessary to train the deep model. In practice, such annotations are expensive to collect and can be scarce for medical imaging applications. Therefore, there is significant interest in learning representations from unlabelled raw data. In this paper, we propose a self-supervised learning approach to learn meaningful and transferable representations from medical imaging video without any type of human annotation. We assume that in order to learn such a representation, the model should identify anatomical structures from the unlabelled data. Therefore we force the model to address anatomy-aware tasks with free supervision from the data itself. Specifically, the model is designed to correct the order of a reshuffled video clip and at the same time predict the geometric transformation applied to the video clip. Experiments on fetal ultrasound video show that the proposed approach can effectively learn meaningful and strong representations, which transfer well to downstream tasks like standard plane detection and saliency prediction.Comment: ISBI 202

Self-Supervised Ultrasound to MRI Fetal Brain Image Synthesis

Fetal brain magnetic resonance imaging (MRI) offers exquisite images of the developing brain but is not suitable for second-trimester anomaly screening, for which ultrasound (US) is employed. Although expert sonographers are adept at reading US images, MR images which closely resemble anatomical images are much easier for non-experts to interpret. Thus in this paper we propose to generate MR-like images directly from clinical US images. In medical image analysis such a capability is potentially useful as well, for instance for automatic US-MRI registration and fusion. The proposed model is end-to-end trainable and self-supervised without any external annotations. Specifically, based on an assumption that the US and MRI data share a similar anatomical latent space, we first utilise a network to extract the shared latent features, which are then used for MRI synthesis. Since paired data is unavailable for our study (and rare in practice), pixel-level constraints are infeasible to apply. We instead propose to enforce the distributions to be statistically indistinguishable, by adversarial learning in both the image domain and feature space. To regularise the anatomical structures between US and MRI during synthesis, we further propose an adversarial structural constraint. A new cross-modal attention technique is proposed to utilise non-local spatial information, by encouraging multi-modal knowledge fusion and propagation. We extend the approach to consider the case where 3D auxiliary information (e.g., 3D neighbours and a 3D location index) from volumetric data is also available, and show that this improves image synthesis. The proposed approach is evaluated quantitatively and qualitatively with comparison to real fetal MR images and other approaches to synthesis, demonstrating its feasibility of synthesising realistic MR images.Comment: IEEE Transactions on Medical Imaging 202

Clinical impact of the methodological quality of fetal doppler standards in the management of fetal growth restriction

Esta tesis, que lleva por título “Clinical impact of the methodological quality of fetal Doppler standards in the management of fetal growth Restriction”, es un trabajo realizado en la Universidad de Zaragoza con colaboración de la Universidad de Oxford por lo que opta a la mención internacional. Además, está elaborada según la normativa de la Universidad de Zaragoza como tesis por compendio de publicaciones, con 4 artículos publicados en revistas de elevado factor de impacto.El crecimiento intrauterino restringido (CIR) es una de las enfermedades con mayor repercusión médica, social y económica en obstetricia. Estos fetos pueden interrumpir su crecimiento como consecuencia de una insuficiencia placentaria, apareciendo alteraciones en el Doppler fetal, lo que conlleva un riesgo elevado de resultado perinatal adverso. Para que una herramienta como el Doppler fetal sea fiable, los valores obtenidos deben ser adecuados y reproducibles, la medición del Doppler debe estar estandarizada y así, maximizaremos su potencial en la evaluación del CIR en la práctica clínica. Con este objetivo se desarrolló la primera de las publicaciones que propone un sistema de puntuación objetiva para evaluar imágenes Doppler de la arteria cerebral media (ACM), demostrando que los controles de calidad de imágenes son esenciales, así como el uso de sistemas objetivos que hagan que las imágenes sean reproducibles.Por otro lado, la secuencia de progresión del Doppler fetal ha sido descrita claramente y hay evidencia de que los cambios cualitativos en el Doppler de la arterial umbilical (AU), como la presencia, ausencia o inversión del flujo diastólico, indican un mayor riesgo de muerte fetal. Sin embargo, la asociación entre los cambios semi-cuantitativos en el Doppler de AU y ACM (medidos con el índice de pulsatilidad) y los resultados perinatales y a largo plazo no se han establecido claramente. Como consecuencia, se han publicado multitud de valores de referencia del índice de pulsatilidad del Doppler fetal. Esta falta de evidencia podría explicarse, al menos parcialmente, por la calidad metodología utilizada para establecer estos valores, lo que podría tener importantes implicaciones para la práctica clínica. Con esta hipótesis, en el segundo trabajo se realizó una revisión sistemática de todos los estudios publicados con el objetivo de crear curvas de referencia para la AU, ACM e índice cerebroplacentario (ICP). Tras utilizar una lista de verificación ya validada y evaluar 38 estudios, se llegó a la conclusión de que todos los estudios en los que se basan los valores de referencia que se usan en la práctica clínica tienen numerosos sesgos metodológicos, haciendo que las diferencias entre los valores sean importantes. Además, en el tercer estudio, se comparó todos estos valores demostrando su gran variabilidad y se realizó una simulación clínica en la que se observó que el manejo de un feto con crecimiento intrauterino restringido puede variar en dependencia del valor de referencia que se elija, decidiendo finalizar la gestación o no y produciendo en algunos casos prematuridad iatrogénica y en otros, aumento del riesgo de muerte fetal intrauterina.Finalmente, como solución a todos los problemas planteados y a la falta de estudios de alta calidad metodológica en los que basar nuestras actuaciones médicas, se propone el estudio FETHUS, un estudio de cohortes, longitudinal, multicéntrico, internacional y prospectivo, con el objetivo de crear unos valores de referencia basados en un estudio con alta calidad metodológica que sirvan de referencia universal para el Doppler fetal, unificando así el manejo del feto con crecimiento intrauterino restringido.1. Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Vol. 2017, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2017. 2. Alfirevic Z, Stampalija T, Medley N. Fetal and umbilical Doppler ultrasound in normal pregnancy. Vol. 2015, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2015. 3. Fetal Growth Restriction. Practice Bulletin No. 134. American College of Obstetricians & Gyncologists. Obstet Gynecol. 2013;4. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol [Internet]. 2016 Sep [cited 2019 Aug 3];48(3):333–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/269096645. RCOG Green-top Guideline, 2nd Edition J 2014. Investigation and Management of the Small for Gestational Age Fetus. R Coll Obstet Gynaecol (RCOG) [Internet]. Available from: http://www.rcog.org.uk/files/rcog-corp/6. Conde-Agudelo A, Villar J, Kennedy SH, Papageorghiou AT. Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018; 7. Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E, Hernandez-Andrade E, et al. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol [Internet]. 2010 Apr [cited 2019 Aug 22];35(4):456–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/201781158. DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Vol. 213, American Journal of Obstetrics and Gynecology. Mosby Inc.; 2015. p. 5–15. 9. Arduini D, Rizzo G. Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med [Internet]. 1990 [cited 2019 Aug 3];18(3):165–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/220086210. Morales-Roselló J, Diaz García-Donato J. Study of fetal femoral and umbilical artery blood flow by Doppler ultrasound throughout pregnancy.11. Figueras F, Gardosi J. Intrauterine growth restriction: New concepts in antenatal surveillance, diagnosis, and management. Vol. 204, American Journal of Obstetrics and Gynecology. Mosby Inc.; 2011. p. 288–300.12. Royston P, Wright EM. How to construct “normal ranges” for fetal variables. Ultrasound Obstet Gynecol. 1998;11(1):30–8.13. Ruiz-Martinez S, Volpe G, Vannuccini S, Cavallaro A, Impey L, Ioannou C. An objective scoring method to evaluate image quality of middle cerebral artery Doppler. J Matern Fetal Neonatal Med [Internet]. 2018 Jun 27 [cited 2019 Sep 12];1–181. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2995015614. Salomon LJ, Bernard JP, Duyme M, Buvat I, Ville Y. The impact of choice of reference charts and equations on the assessment of fetal biometry. Ultrasound Obstet Gynecol. 2005 Jun;25(6):559–65.<br /

Discovering Salient Anatomical Landmarks by Predicting Human Gaze

Anatomical landmarks are a crucial prerequisite for many medical imaging tasks. Usually, the set of landmarks for a given task is predefined by experts. The landmark locations for a given image are then annotated manually or via machine learning methods trained on manual annotations. In this paper, in contrast, we present a method to automatically discover and localize anatomical landmarks in medical images. Specifically, we consider landmarks that attract the visual attention of humans, which we term visually salient landmarks. We illustrate the method for fetal neurosonographic images. First, full-length clinical fetal ultrasound scans are recorded with live sonographer gaze-tracking. Next, a convolutional neural network (CNN) is trained to predict the gaze point distribution (saliency map) of the sonographers on scan video frames. The CNN is then used to predict saliency maps of unseen fetal neurosonographic images, and the landmarks are extracted as the local maxima of these saliency maps. Finally, the landmarks are matched across images by clustering the landmark CNN features. We show that the discovered landmarks can be used within affine image registration, with average landmark alignment errors between 4.1% and 10.9% of the fetal head long axis length.Comment: Accepted at IEEE International Symposium on Biomedical Imaging 2020 (ISBI 2020

Show from Tell: Audio-Visual Modelling in Clinical Settings

Auditory and visual signals usually present together and correlate with each other, not only in natural environments but also in clinical settings. However, the audio-visual modelling in the latter case can be more challenging, due to the different sources of audio/video signals and the noise (both signal-level and semantic-level) in auditory signals -- usually speech. In this paper, we consider audio-visual modelling in a clinical setting, providing a solution to learn medical representations that benefit various clinical tasks, without human expert annotation. A simple yet effective multi-modal self-supervised learning framework is proposed for this purpose. The proposed approach is able to localise anatomical regions of interest during ultrasound imaging, with only speech audio as a reference. Experimental evaluations on a large-scale clinical multi-modal ultrasound video dataset show that the proposed self-supervised method learns good transferable anatomical representations that boost the performance of automated downstream clinical tasks, even outperforming fully-supervised solutions

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertensió gestacional; PreeclampsiaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertension gestacional; PreeclampsiaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Gestational hypertension; PreeclampsiaBackground It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.The study was supported by the COVID-19 Research Response Fund from the University of Oxford (Ref 0009083). A.T.P. is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the National Institute for Health Research (NIHR) Biomedical Research Centre funding scheme. The funding organization had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication

"You cannot know if it's a baby or not a baby": uptake, provision and perceptions of antenatal care and routine antenatal ultrasound scanning in rural Kenya.

BACKGROUND: Antenatal care early in pregnancy enables service providers to identify and manage risks to mother and fetus. In the global north, ultrasound scans are routinely offered in pregnancy to provide an accurate estimate of gestational age and identify potential problems. In sub-Saharan Africa, such services are rarely available and women often delay initiating antenatal care. This study describes the uptake and provision of antenatal care in a rural Kenyan hospital and explores how pregnant women and healthcare providers perceived the provision of ultrasound scanning, following its introduction in an international foetal growth study. METHODS: A descriptive study, using qualitative and quantitative methods, was conducted in Kilifi District Hospital, Kenya, between June 2011 and April 2012. In-depth interviews were conducted with 10 nurses working in the antenatal clinic (ANC) and 59 pregnant women attending ANC. Structured observations of 357 ANC consultations and 30 ultrasound scans were made. RESULTS: Women sought antenatal care for information about the health of their baby and the protection provided by the ANC services. Uncertainty about pregnancy status contributed to delay in ANC attendance; more than 78 % of women were over 20 weeks' gestation at their first visit. Healthcare workers found it difficult to detect pregnancies below 16 weeks gestation and, accurate assessment of gestational age below 20 weeks' gestation could be problematic. Provision of services depended on the pregnancy being detected and gestational age assessed. The "seeing", made possible through ultrasound scanning was perceived by pregnant women and healthcare workers to be beneficial: confirming the pregnancy, and providing reassurance about the fetus' condition. Few participants raised concerns about ultrasound scanning. CONCLUSIONS: Uncertainty about pregnancy status and gestational age for women and healthcare providers is a key factor influencing timing of ANC attendance, contributing to delays and restricting early provision of ANC services. Ultrasound scanning was perceived to enhance antenatal care through confirmation of pregnancy status and enabling more accurate estimation of gestational age and the health status of the fetus. There is a need to make available more affordable means of pregnancy testing as a strategy towards encouraging early attendance, and delivery of antenatal care

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.UNLABELLED: MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. BACKGROUND: Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. METHODS/DESIGN: Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. DISCUSSION: As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.Published versio

Association between preterm-birth phenotypes and differential morbidity, growth, and neurodevelopment at age 2 years: Results from the INTERBIO-21st newborn study

Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.Design, setting, and participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020.Exposures/interventions: Preterm-birth phenotypes.Main outcomes and measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype.Conclusions and relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity