DCE-MRI for Early Prediction of Response in Hepatocellular Carcinoma after TACE and Sorafenib Therapy: A Pilot Study

Objective: Dynamic contrast-enhanced MRI (DCE-MRI) can measure the changes in tumor blood flow, vascular permeability and interstitial and intravascular volume. The objective was to evaluate the efficacy of DCE-MRI in prediction of Barcelona Clinic Liver Cancer (BCLC) staging B or C hepatocellular carcinoma (HCC) response after treatment with transcatheter arterial chemoembolization (TACE) followed by sorafenib therapy. Methods: Sorafenib was administered four days after TACE of BCLC staging B or C HCC in 11 patients (21 lesions). DCE-MRI was performed with Gd-EOB-DTPA contrast before TACE and three and 10 days after TACE. DCE-MRI acquisitions were taken pre-contrast, hepatic arterial-dominant phase and 60, 120, 180, 240, 330, 420, 510 and 600 seconds post-contrast. Distribution volume of contrast agent (DV) and transfer constant Ktrans were calculated. Patients were grouped by mRECIST after one month or more post-TACE into responders (complete response, partial response) and non-responders (stable disease, progressive disease). Results: DV was reduced in responders at three and 10 days post-TACE (p = 0.008 and p = 0.008 respectively). DV fell in non-responders at three days (p = 0.025) but was not significantly changed from pre-TACE values after sorafenib. Sensitivity and specificity for DV 10 days post-TACE were 88% and 77% respectively. Conclusion: DV may be a useful biomarker for early prediction of therapeutic outcome in intermediate HCC

Applying machine learning to automated segmentation of head and neck tumour volumes and organs at risk on radiotherapy planning CT and MRI scans

Radiotherapy is one of the main ways head and neck cancers are treated; radiation is used to kill cancerous cells and prevent their recurrence. Complex treatment planning is required to ensure that enough radiation is given to the tumour, and little to other sensitive structures (known as organs at risk) such as the eyes and nerves which might otherwise be damaged. This is especially difficult in the head and neck, where multiple at-risk structures often lie in extremely close proximity to the tumour. It can take radiotherapy experts four hours or more to pick out the important areas on planning scans (known as segmentation). This research will focus on applying machine learning algorithms to automatic segmentation of head and neck planning computed tomography (CT) and magnetic resonance imaging (MRI) scans at University College London Hospital NHS Foundation Trust patients. Through analysis of the images used in radiotherapy DeepMind Health will investigate improvements in efficiency of cancer treatment pathways

Automated analysis of retinal imaging using machine learning techniques for computer vision

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases. Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular (“wet”) age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the ‘back’ of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges. This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients. Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, Google DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success

Feasibility of Automated Deep Learning Design for Medical Image Classification by Healthcare Professionals with Limited Coding Experience

Deep learning has huge potential to transform healthcare. However, significant expertise is required to train such models and this is a significant blocker for their translation into clinical practice. In this study, we therefore sought to evaluate the use of automated deep learning software to develop medical image diagnostic classifiers by healthcare professionals with limited coding – and no deep learning – expertise. We used five publicly available open-source datasets: (i) retinal fundus images (MESSIDOR); (ii) optical coherence tomography (OCT) images (Guangzhou Medical University/Shiley Eye Institute, Version 3); (iii) images of skin lesions (Human against Machine (HAM)10000) and (iv) both paediatric and adult chest X-ray (CXR) images (Guangzhou Medical University/Shiley Eye Institute, Version 3 and the National Institute of Health (NIH)14 dataset respectively) to separately feed into a neural architecture search framework that automatically developed a deep learning architecture to classify common diseases. Sensitivity (recall), specificity and positive predictive value (precision) were used to evaluate the diagnostic properties of the models. The discriminative performance was assessed using the area under the precision recall curve (AUPRC). In the case of the deep learning model developed on a subset of the HAM10000 dataset, we performed external validation using the Edinburgh Dermofit Library dataset. Diagnostic properties and discriminative performance from internal validations were high in the binary classification tasks (range: sensitivity of 73.3-97.0%, specificity of 67-100% and AUPRC of 0.87-1). In the multiple classification tasks, the diagnostic properties ranged from 38-100% for sensitivity and 67-100% for specificity. The discriminative performance in terms of AUPRC ranged from 0.57 to 1 in the five automated deep learning models. In an external validation using the Edinburgh Dermofit Library dataset, the automated deep learning model showed an AUPRC of 0.47, with a sensitivity of 49% and a positive predictive value of 52%. The quality of the open-access datasets used in this study (including the lack of information about patient flow and demographics) and the absence of measurement for precision, such as confidence intervals, constituted the major limitation of this study. All models, except for the automated deep learning model trained on the multi-label classification task of the NIH CXR14 dataset, showed comparable discriminative performance and diagnostic properties to state-of-the-art performing deep learning algorithms. The performance in the external validation study was low. The availability of automated deep learning may become a cornerstone for the democratization of sophisticated algorithmic modelling in healthcare as it allows the derivation of classification models without requiring a deep understanding of the mathematical, statistical and programming principles. Future studies should compare several application programming interfaces on thoroughly curated datasets

Predicting optical coherence tomography-derived diabetic macular edema grades from fundus photographs using deep learning

Center-involved diabetic macular edema (ci-DME) is a major cause of vision loss. Although the gold standard for diagnosis involves 3D imaging, 2D imaging by fundus photography is usually used in screening settings, resulting in high false-positive and false-negative calls. To address this, we train a deep learning model to predict ci-DME from fundus photographs, with an ROC–AUC of 0.89 (95% CI: 0.87–0.91), corresponding to 85% sensitivity at 80% specificity. In comparison, retinal specialists have similar sensitivities (82–85%), but only half the specificity (45–50%, p < 0.001). Our model can also detect the presence of intraretinal fluid (AUC: 0.81; 95% CI: 0.81–0.86) and subretinal fluid (AUC 0.88; 95% CI: 0.85–0.91). Using deep learning to make predictions via simple 2D images without sophisticated 3D-imaging equipment and with better than specialist performance, has broad relevance to many other applications in medical imaging

Service evaluation of the implementation of a digitally-enabled care pathway for the recognition and management of acute kidney injury

Acute Kidney Injury (AKI), an abrupt deterioration in kidney function, is defined by changes in urine output or serum creatinine. AKI is common (affecting up to 20% of acute hospital admissions in the United Kingdom), associated with significant morbidity and mortality, and expensive (excess costs to the National Health Service in England alone may exceed £1 billion per year). NHS England has mandated the implementation of an automated algorithm to detect AKI based on changes in serum creatinine, and to alert clinicians. It is uncertain, however, whether ‘alerting’ alone improves care quality. We have thus developed a digitally-enabled care pathway as a clinical service to inpatients in the Royal Free Hospital (RFH), a large London hospital. This pathway incorporates a mobile software application - the “Streams-AKI” app, developed by DeepMind Health - that applies the NHS AKI algorithm to routinely collected serum creatinine data in hospital inpatients. Streams-AKI alerts clinicians to potential AKI cases, furnishing them with a trend view of kidney function alongside other relevant data, in real-time, on a mobile device. A clinical response team comprising nephrologists and critical care nurses responds to these AKI alerts by reviewing individual patients and administering interventions according to existing clinical practice guidelines. We propose a mixed methods service evaluation of the implementation of this care pathway. This evaluation will assess how the care pathway meets the health and care needs of service users (RFH inpatients), in terms of clinical outcome, processes of care, and NHS costs. It will also seek to assess acceptance of the pathway by members of the response team and wider hospital community. All analyses will be undertaken by the service evaluation team from UCL (Department of Applied Health Research) and St George’s, University of London (Population Health Research Institute)

Deep Learning for Predicting Refractive Error From Retinal Fundus Images

PURPOSE. We evaluate how deep learning can be applied to extract novel information such as refractive error from retinal fundus imaging. METHODS. Retinal fundus images used in this study were 45- and 30-degree field of view images from the UK Biobank and Age-Related Eye Disease Study (AREDS) clinical trials, respectively. Refractive error was measured by autorefraction in UK Biobank and subjective refraction in AREDS. We trained a deep learning algorithm to predict refractive error from a total of 226,870 images and validated it on 24,007 UK Biobank and 15,750 AREDS images. Our model used the ‘‘attention’’ method to identify features that are correlated with refractive error. RESULTS. The resulting algorithm had a mean absolute error (MAE) of 0.56 diopters (95% confidence interval [CI]: 0.55–0.56) for estimating spherical equivalent on the UK Biobank data set and 0.91 diopters (95% CI: 0.89–0.93) for the AREDS data set. The baseline expected MAE (obtained by simply predicting the mean of this population) was 1.81 diopters (95% CI: 1.79–1.84) for UK Biobank and 1.63 (95% CI: 1.60–1.67) for AREDS. Attention maps suggested that the foveal region was one of the most important areas used by the algorithm to make this prediction, though other regions also contribute to the prediction. CONCLUSIONS. To our knowledge, the ability to estimate refractive error with high accuracy from retinal fundus photos has not been previously known and demonstrates that deep learning can be applied to make novel predictions from medical images

Clinically Applicable Segmentation of Head and Neck Anatomy for Radiotherapy: Deep Learning Algorithm Development and Validation Study

BACKGROUND: Over half a million individuals are diagnosed with head and neck cancer each year globally. Radiotherapy is an important curative treatment for this disease, but it requires manual time to delineate radiosensitive organs at risk. This planning process can delay treatment while also introducing interoperator variability, resulting in downstream radiation dose differences. Although auto-segmentation algorithms offer a potentially time-saving solution, the challenges in defining, quantifying, and achieving expert performance remain. OBJECTIVE: Adopting a deep learning approach, we aim to demonstrate a 3D U-Net architecture that achieves expert-level performance in delineating 21 distinct head and neck organs at risk commonly segmented in clinical practice. METHODS: The model was trained on a data set of 663 deidentified computed tomography scans acquired in routine clinical practice and with both segmentations taken from clinical practice and segmentations created by experienced radiographers as part of this research, all in accordance with consensus organ at risk definitions. RESULTS: We demonstrated the model's clinical applicability by assessing its performance on a test set of 21 computed tomography scans from clinical practice, each with 21 organs at risk segmented by 2 independent experts. We also introduced surface Dice similarity coefficient, a new metric for the comparison of organ delineation, to quantify the deviation between organ at risk surface contours rather than volumes, better reflecting the clinical task of correcting errors in automated organ segmentations. The model's generalizability was then demonstrated on 2 distinct open-source data sets, reflecting different centers and countries to model training. CONCLUSIONS: Deep learning is an effective and clinically applicable technique for the segmentation of the head and neck anatomy for radiotherapy. With appropriate validation studies and regulatory approvals, this system could improve the efficiency, consistency, and safety of radiotherapy pathways

Use of deep learning to develop continuous-risk models for adverse event prediction from electronic health records

Early prediction of patient outcomes is important for targeting preventive care. This protocol describes a practical workflow for developing deep-learning risk models that can predict various clinical and operational outcomes from structured electronic health record (EHR) data. The protocol comprises five main stages: formal problem definition, data pre-processing, architecture selection, calibration and uncertainty, and generalizability evaluation. We have applied the workflow to four endpoints (acute kidney injury, mortality, length of stay and 30-day hospital readmission). The workflow can enable continuous (e.g., triggered every 6 h) and static (e.g., triggered at 24 h after admission) predictions. We also provide an open-source codebase that illustrates some key principles in EHR modeling. This protocol can be used by interdisciplinary teams with programming and clinical expertise to build deep-learning prediction models with alternate data sources and prediction tasks

International evaluation of an AI system for breast cancer screening.

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful1. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives2. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.Professor Fiona Gilbert receives funding from the National Institute for Health Research (Senior Investigator award)