Lung cancer prediction by Deep Learning to identify benign lung nodules.

INTRODUCTION: Deep Learning has been proposed as promising tool to classify malignant nodules. Our aim was to retrospectively validate our Lung Cancer Prediction Convolutional Neural Network (LCP-CNN), which was trained on US screening data, on an independent dataset of indeterminate nodules in an European multicentre trial, to rule out benign nodules maintaining a high lung cancer sensitivity. METHODS: The LCP-CNN has been trained to generate a malignancy score for each nodule using CT data from the U.S. National Lung Screening Trial (NLST), and validated on CT scans containing 2106 nodules (205 lung cancers) detected in patients from from the Early Lung Cancer Diagnosis Using Artificial Intelligence and Big Data (LUCINDA) study, recruited from three tertiary referral centers in the UK, Germany and Netherlands. We pre-defined a benign nodule rule-out test, to identify benign nodules whilst maintaining a high sensitivity, by calculating thresholds on the malignancy score that achieve at least 99 % sensitivity on the NLST data. Overall performance per validation site was evaluated using Area-Under-the-ROC-Curve analysis (AUC). RESULTS: The overall AUC across the European centers was 94.5 % (95 %CI 92.6-96.1). With a high sensitivity of 99.0 %, malignancy could be ruled out in 22.1 % of the nodules, enabling 18.5 % of the patients to avoid follow-up scans. The two false-negative results both represented small typical carcinoids. CONCLUSION: The LCP-CNN, trained on participants with lung nodules from the US NLST dataset, showed excellent performance on identification of benign lung nodules in a multi-center external dataset, ruling out malignancy with high accuracy in about one fifth of the patients with 5-15 mm nodules.

Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules.

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

Processing citizen science- and machine-annotated time-lapse imagery for biologically meaningful metrics.

Time-lapse cameras facilitate remote and high-resolution monitoring of wild animal and plant communities, but the image data produced require further processing to be useful. Here we publish pipelines to process raw time-lapse imagery, resulting in count data (number of penguins per image) and 'nearest neighbour distance' measurements. The latter provide useful summaries of colony spatial structure (which can indicate phenological stage) and can be used to detect movement - metrics which could be valuable for a number of different monitoring scenarios, including image capture during aerial surveys. We present two alternative pathways for producing counts: (1) via the Zooniverse citizen science project Penguin Watch and (2) via a computer vision algorithm (Pengbot), and share a comparison of citizen science-, machine learning-, and expert- derived counts. We provide example files for 14 Penguin Watch cameras, generated from 63,070 raw images annotated by 50,445 volunteers. We encourage the use of this large open-source dataset, and the associated processing methodologies, for both ecological studies and continued machine learning and computer vision development.

External validation of a convolutional neural network artificial intelligence tool to predict malignancy in pulmonary nodules.

BACKGROUND: Estimation of the risk of malignancy in pulmonary nodules detected by CT is central in clinical management. The use of artificial intelligence (AI) offers an opportunity to improve risk prediction. Here we compare the performance of an AI algorithm, the lung cancer prediction convolutional neural network (LCP-CNN), with that of the Brock University model, recommended in UK guidelines. METHODS: A dataset of incidentally detected pulmonary nodules measuring 5-15 mm was collected retrospectively from three UK hospitals for use in a validation study. Ground truth diagnosis for each nodule was based on histology (required for any cancer), resolution, stability or (for pulmonary lymph nodes only) expert opinion. There were 1397 nodules in 1187 patients, of which 234 nodules in 229 (19.3%) patients were cancer. Model discrimination and performance statistics at predefined score thresholds were compared between the Brock model and the LCP-CNN. RESULTS: The area under the curve for LCP-CNN was 89.6% (95% CI 87.6 to 91.5), compared with 86.8% (95% CI 84.3 to 89.1) for the Brock model (p≤0.005). Using the LCP-CNN, we found that 24.5% of nodules scored below the lowest cancer nodule score, compared with 10.9% using the Brock score. Using the predefined thresholds, we found that the LCP-CNN gave one false negative (0.4% of cancers), whereas the Brock model gave six (2.5%), while specificity statistics were similar between the two models. CONCLUSION: The LCP-CNN score has better discrimination and allows a larger proportion of benign nodules to be identified without missing cancers than the Brock model. This has the potential to substantially reduce the proportion of surveillance CT scans required and thus save significant resources.

Non-contact physiological monitoring of preterm infants in the Neonatal Intensive Care Unit.

The implementation of video-based non-contact technologies to monitor the vital signs of preterm infants in the hospital presents several challenges, such as the detection of the presence or the absence of a patient in the video frame, robustness to changes in lighting conditions, automated identification of suitable time periods and regions of interest from which vital signs can be estimated. We carried out a clinical study to evaluate the accuracy and the proportion of time that heart rate and respiratory rate can be estimated from preterm infants using only a video camera in a clinical environment, without interfering with regular patient care. A total of 426.6 h of video and reference vital signs were recorded for 90 sessions from 30 preterm infants in the Neonatal Intensive Care Unit (NICU) of the John Radcliffe Hospital in Oxford. Each preterm infant was recorded under regular ambient light during daytime for up to four consecutive days. We developed multi-task deep learning algorithms to automatically segment skin areas and to estimate vital signs only when the infant was present in the field of view of the video camera and no clinical interventions were undertaken. We propose signal quality assessment algorithms for both heart rate and respiratory rate to discriminate between clinically acceptable and noisy signals. The mean absolute error between the reference and camera-derived heart rates was 2.3 beats/min for over 76% of the time for which the reference and camera data were valid. The mean absolute error between the reference and camera-derived respiratory rate was 3.5 breaths/min for over 82% of the time. Accurate estimates of heart rate and respiratory rate could be derived for at least 90% of the time, if gaps of up to 30 seconds with no estimates were allowed.

Cardio-respiratory signal extraction from video camera data for continuous non-contact vital sign monitoring using deep learning.

Non-contact vital sign monitoring enables the estimation of vital signs, such as heart rate, respiratory rate and oxygen saturation (SpO2), by measuring subtle color changes on the skin surface using a video camera. For patients in a hospital ward, the main challenges in the development of continuous and robust non-contact monitoring techniques are the identification of time periods and the segmentation of skin regions of interest (ROIs) from which vital signs can be estimated. We propose a deep learning framework to tackle these challenges. APPROACH: This paper presents two convolutional neural network (CNN) models. The first network was designed for detecting the presence of a patient and segmenting the patient's skin area. The second network combined the output from the first network with optical flow for identifying time periods of clinical intervention so that these periods can be excluded from the estimation of vital signs. Both networks were trained using video recordings from a clinical study involving 15 pre-term infants conducted in the high dependency area of the neonatal intensive care unit (NICU) of the John Radcliffe Hospital in Oxford, UK. MAIN RESULTS: Our proposed methods achieved an accuracy of 98.8% for patient detection, a mean intersection-over-union (IOU) score of 88.6% for skin segmentation and an accuracy of 94.5% for clinical intervention detection using two-fold cross validation. Our deep learning models produced accurate results and were robust to different skin tones, changes in light conditions, pose variations and different clinical interventions by medical staff and family visitors. SIGNIFICANCE: Our approach allows cardio-respiratory signals to be continuously derived from the patient's skin during which the patient is present and no clinical intervention is undertaken.

Author Correction: Time-lapse imagery and volunteer classifications from the Zooniverse Penguin Watch project.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Time-lapse imagery and volunteer classifications from the Zooniverse Penguin Watch project.

Automated time-lapse cameras can facilitate reliable and consistent monitoring of wild animal populations. In this report, data from 73,802 images taken by 15 different Penguin Watch cameras are presented, capturing the dynamics of penguin (Spheniscidae; Pygoscelis spp.) breeding colonies across the Antarctic Peninsula, South Shetland Islands and South Georgia (03/2012 to 01/2014). Citizen science provides a means by which large and otherwise intractable photographic data sets can be processed, and here we describe the methodology associated with the Zooniverse project Penguin Watch, and provide validation of the method. We present anonymised volunteer classifications for the 73,802 images, alongside the associated metadata (including date/time and temperature information). In addition to the benefits for ecological monitoring, such as easy detection of animal attendance patterns, this type of annotated time-lapse imagery can be employed as a training tool for machine learning algorithms to automate data extraction, and we encourage the use of this data set for computer vision development.

Crystal nucleation in metallic alloys using x-ray radiography and machine learning.

The crystallization of solidifying Al-Cu alloys over a wide range of conditions was studied in situ by synchrotron x-ray radiography, and the data were analyzed using a computer vision algorithm trained using machine learning. The effect of cooling rate and solute concentration on nucleation undercooling, crystal formation rate, and crystal growth rate was measured automatically for thousands of separate crystals, which was impossible to achieve manually. Nucleation undercooling distributions confirmed the efficiency of extrinsic grain refiners and gave support to the widely assumed free growth model of heterogeneous nucleation. We show that crystallization occurred in temporal and spatial bursts associated with a solute-suppressed nucleation zone.

Detecting overlapping instances in microscopy images using extremal region trees.

In many microscopy applications the images may contain both regions of low and high cell densities corresponding to different tissues or colonies at different stages of growth. This poses a challenge to most previously developed automated cell detection and counting methods, which are designed to handle either the low-density scenario (through cell detection) or the high-density scenario (through density estimation or texture analysis). The objective of this work is to detect all the instances of an object of interest in microscopy images. The instances may be partially overlapping and clustered. To this end we introduce a tree-structured discrete graphical model that is used to select and label a set of non-overlapping regions in the image by a global optimization of a classification score. Each region is labeled with the number of instances it contains - for example regions can be selected that contain two or three object instances, by defining separate classes for tuples of objects in the detection process. We show that this formulation can be learned within the structured output SVM framework and that the inference in such a model can be accomplished using dynamic programming on a tree structured region graph. Furthermore, the learning only requires weak annotations - a dot on each instance. The candidate regions for the selection are obtained as extremal region of a surface computed from the microscopy image, and we show that the performance of the model can be improved by considering a proxy problem for learning the surface that allows better selection of the extremal regions. Furthermore, we consider a number of variations for the loss function used in the structured output learning. The model is applied and evaluated over six quite disparate data sets of images covering: fluorescence microscopy, weak-fluorescence molecular images, phase contrast microscopy and histopathology images, and is shown to exceed the state of the art in performance.

Learning to detect cells using non-overlapping extremal regions.

Cell detection in microscopy images is an important step in the automation of cell based-experiments. We propose a machine learning-based cell detection method applicable to different modalities. The method consists of three steps: first, a set of candidate cell-like regions is identified. Then, each candidate region is evaluated using a statistical model of the cell appearance. Finally, dynamic programming picks a set of non-overlapping regions that match the model. The cell model requires few images with simple dot annotation for training and can be learned within a structured SVM framework. In the reported experiments, state-of-the-art cell detection accuracy is achieved for H&E stained histology, fluorescence, and phase-contrast images.

Estudio clínico de la epilepsia mioclónica juvenil

El objetivo de este trabajo es evaluar la frecuencia de presentación, características clínicas y respuesta al tratamiento en escolares y adolescentes con diagnóstico de epilepsia mioclónica juvenil. Es un estudio retrospectivo de una serie de casos de niños con epilepsia mioclónica juvenil del Servicio de Neurología Infantil del Hospital Militar Central (HMC) en el período comprendido entre el 1o. de noviembre de 1989 y el 31 de octubre de 1991. Se recopilaron 17 pacientes durante el período de tiempo evaluado, con un predominio de mujeres 12/17 casos. La distribución por edad osciló entre los ocho y los 14 años siendo más frecuente entre los ocho y los diez años. Los antecedentes familiares de epilepsia primaria fueron positivos en 30 por ciento, mioclonías asociadas a crisis tónico-clónicas generalizadas en 12 por ciento. El tratamiento instaurado con ácido valproico se realizó en 16/17 pacientes obteniéndose control de las crisis en 81 por ciento; 3/17 pacientes requirieron asociación de clobazam con ácido valproico para el control; un paciente se manejó con clobazam únicamente. La epilepsia mioclónica juvenil es el síndrome epiléptico primario más frecuente encontrado en el grupo de escolares y adolescentes de la Clínica de Epilepsia del Servicio de Neurología Infantil de HMC. La sospecha clínica de esta entidad es básica para un diagnóstico adecuado, especialmente cuando el primero o el único tipo de crisis son mioclonías matinales.