Background Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

No abstract

Cardiovascular disease (CVD) is the number one cause of death worldwide, and coronary artery disease (CAD) is the most prevalent CVD, accounting for 42% of these deaths. In view of the limitations of the anatomical evaluation of CAD, Fractional Flow Reserve (FFR) has been introduced as a functional diagnostic index. Herein, we evaluate the feasibility of using deep neural networks (DNN) in an ensemble approach to predict the invasively measured FFR from raw anatomical information that is extracted from optical coherence tomography (OCT). We evaluate the performance of various DNN architectures under different formulations: regression, classification—standard, and few-shot learning (FSL) on a dataset containing 102 intermediate lesions from 80 patients. The FSL approach that is based on a convolutional neural network leads to slightly better results compared to the standard classification: the per-lesion accuracy, sensitivity, and specificity were 77.5%, 72.9%, and 81.5%, respectively. However, since the 95% confidence intervals overlap, the differences are statistically not significant. The main findings of this study can be summarized as follows: (1) Deep-learning (DL)-based FFR prediction from reduced-order raw anatomical data is feasible in intermediate coronary artery lesions; (2) DL-based FFR prediction provides superior diagnostic performance compared to baseline approaches that are based on minimal lumen diameter and percentage diameter stenosis; and (3) the FFR prediction performance increases quasi-linearly with the dataset size, indicating that a larger train dataset will likely lead to superior diagnostic performance.

No abstract

No abstract

A nonlinear model consisting of a system of coupled ordinary differential equations (ODE), describing a biological process linked with cancer development, is linearized using Taylor series and tested against different magnitudes of input perturbations, in order to investigate the extent to which the linearization is accurate. The canonical wingless/integrated (WNT) signaling pathway is considered. The linearization procedure is described, and special considerations for linearization validity are analyzed. The analytical properties of nonlinear and linearized systems are studied, including aspects such as existence of steady state and initial value sensitivity. Linearization is a useful tool for speeding up drug response computations or for providing analytical answers to problems such as required drug concentrations. A Monte Carlo-based error testing workflow is employed to study the errors introduced by the linearization for different input conditions and parameter vectors. The deviations between the nonlinear and the linearized system were found to increase in a polynomial fashion w.r.t. the magnitude of tested perturbations. The linearized system closely followed the original one for perturbations of magnitude within 10% of the base input vector which yielded the state-space fixed point used for the linearization.

No abstract

Invasive coronary angiography (ICA) is the gold standard in Coronary Artery Disease (CAD) imaging. Detection of the end-diastolic frame (EDF) and, in general, cardiac phase detection on each temporal frame of a coronary angiography acquisition is of significant importance for the anatomical and non-invasive functional assessment of CAD. This task is generally performed via manual frame selection or semi-automated selection based on simultaneously acquired ECG signals -thus introducing the requirement of simultaneous ECG recordings. In this paper, we evaluate the performance of a purely image based workflow based on deep neural networks for fully automated cardiac phase and EDF detection on coronary angiographies. A first deep neural network (DNN), trained to detect coronary arteries, is employed to preselect a subset of frames in which coronary arteries are well visible. A second DNN predicts cardiac phase labels for each frame. Only in the training and evaluation phases for the second DNN, ECG signals are used to provide ground truth labels for each angiographic frame. The networks were trained on 17800 coronary angiographies from 3900 patients and evaluated on 27900 coronary angiographies from 6250 patients. No exclusion criteria related to patient state (stable or acute CAD), previous interventions (PCI or CABG), or pathology were formulated. Cardiac phase detection had an accuracy of 97.6%, a sensitivity of 97.6% and a specificity of 97.5% on the evaluation set. EDF prediction had a precision of 97.4% and a recall of 96.9%. Several sub-group analyses were performed, indicating that the cardiac phase detection performance is largely independent from acquisition angles and the heart rate of the patient, and that the detection accuracy is slightly higher for the left coronary artery than for the right coronary artery. The average execution time of cardiac phase detection for one angiographic series was on average less than five seconds on a standard workstation. We conclude that the proposed image based workflow potentially obviates the need for manual frame selection and ECG acquisition, representing a relevant step towards automated CAD assessment.