From Bit To Bedside: A Practical Framework For Artificial Intelligence Product Development In Healthcare

Artificial Intelligence (AI) in healthcare holds great potential to expand access to high-quality medical care, whilst reducing overall systemic costs. Despite hitting the headlines regularly and many publications of proofs-of-concept, certified products are failing to breakthrough to the clinic. AI in healthcare is a multi-party process with deep knowledge required in multiple individual domains. The lack of understanding of the specific challenges in the domain is, therefore, the major contributor to the failure to deliver on the big promises. Thus, we present a decision perspective framework, for the development of AI-driven biomedical products, from conception to market launch. Our framework highlights the risks, objectives and key results which are typically required to proceed through a three-phase process to the market launch of a validated medical AI product. We focus on issues related to Clinical validation, Regulatory affairs, Data strategy and Algorithmic development. The development process we propose for AI in healthcare software strongly diverges from modern consumer software development processes. We highlight the key time points to guide founders, investors and key stakeholders throughout their relevant part of the process. Our framework should be seen as a template for innovation frameworks, which can be used to coordinate team communications and responsibilities towards a reasonable product development roadmap, thus unlocking the potential of AI in medicine.Comment: 30 pages, 4 figure

A trustworthy AI reality-check: the lack of transparency of artificial intelligence products in healthcare

Trustworthy medical AI requires transparency about the development and testing of underlying algorithms to identify biases and communicate potential risks of harm. Abundant guidance exists on how to achieve transparency for medical AI products, but it is unclear whether publicly available information adequately informs about their risks. To assess this, we retrieved public documentation on the 14 available CE-certified AI-based radiology products of the II b risk category in the EU from vendor websites, scientific publications, and the European EUDAMED database. Using a self-designed survey, we reported on their development, validation, ethical considerations, and deployment caveats, according to trustworthy AI guidelines. We scored each question with either 0, 0.5, or 1, to rate if the required information was “unavailable”, “partially available,” or “fully available.” The transparency of each product was calculated relative to all 55 questions. Transparency scores ranged from 6.4% to 60.9%, with a median of 29.1%. Major transparency gaps included missing documentation on training data, ethical considerations, and limitations for deployment. Ethical aspects like consent, safety monitoring, and GDPR-compliance were rarely documented. Furthermore, deployment caveats for different demographics and medical settings were scarce. In conclusion, public documentation of authorized medical AI products in Europe lacks sufficient public transparency to inform about safety and risks. We call on lawmakers and regulators to establish legally mandated requirements for public and substantive transparency to fulfill the promise of trustworthy AI for health

Hybrid Modelling for Stroke Care: Review and suggestions of new approaches for risk assessment and simulation of scenarios

Stroke is an example of a complex and multi-factorial disease involving multiple organs, timescales, and disease mechanisms. To deal with this complexity, and to realize Precision Medicine of stroke, mathematical models are needed. Such approaches include: 1) machine learning, 2) bioinformatic network models, and 3) mechanistic models. Since these three approaches have complementary strengths and weaknesses, a hybrid modelling approach combining them would be the most beneficial. However, no concrete approach ready to be implemented for a specific disease has been presented to date. In this paper, we both review the strengths and weaknesses of the three approaches, and propose a roadmap for hybrid modelling in the case of stroke care. We focus on two main tasks needed for the clinical setting: a) For stroke risk calculation, we propose a new two-step approach, where non-linear mixed effects models and bioinformatic network models yield biomarkers which are used as input to a machine learning model and b) For simulation of care scenarios, we propose a new four-step approach, which revolves around iterations between simulations of the mechanistic models and imputations of non-modelled or non-measured variables. We illustrate and discuss the different approaches in the context of Precision Medicine for stroke

Multimodal Fusion Strategies for Outcome Prediction in Stroke

Data driven methods are increasingly being adopted in the medical domain for clinical predictive modeling. Prediction of stroke outcome using machine learning could provide a decision support system for physicians to assist them in patient-oriented diagnosis and treatment. While patient-specific clinical parameters play an important role in outcome prediction, a multimodal fusion approach that integrates neuroimaging with clinical data has the potential to improve accuracy. This paper addresses two research questions: (a) does multimodal fusion aid in the prediction of stroke outcome, and (b) what fusion strategy is more suitable for the task at hand. The baselines for our experimental work are two unimodal neural architectures: a 3D Convolutional Neural Network for processing neuroimaging data, and a Multilayer Perceptron for processing clinical data. Using these unimodal architectures as building blocks we propose two feature-level multimodal fusion strategies: 1) extracted features , where the unimodal architectures are trained separately and then fused, and 2) end-to-end, where the unimodal architectures are trained together. We show that integration of neuroimaging information with clinical metadata can potentially improve stroke outcome prediction. Additionally, experimental results indicate that the end-to-end fusion approach proves to be more robust

A precision medicine framework for personalized simulation of hemodynamics in cerebrovascular disease

Background: Cerebrovascular disease, in particular stroke, is a major public health challenge. An important biomarker is cerebral hemodynamics. To measure and quantify cerebral hemodynamics, however, only invasive, potentially harmful or time-to-treatment prolonging methods are available. Results: We present a simulation-based approach which allows calculation of cerebral hemodynamics based on the patient-individual vessel configuration derived from structural vessel imaging. For this, we implemented a framework allowing segmentation and annotation of brain vessels from structural imaging followed by 0-dimensional lumped simulation modeling of cerebral hemodynamics. For annotation, a 3D-graphical user interface was implemented. For 0D-simulation, we used a modified nodal analysis, which was adapted for easy implementation by code. The simulation enables identification of areas vulnerable to stroke and simulation of changes due to different systemic blood pressures. Moreover, sensitivity analysis was implemented allowing the live simulation of changes to simulate procedures and disease progression. Beyond presentation of the framework, we demonstrated in an exploratory analysis in 67 patients that the simulation has a high specificity and low-to-moderate sensitivity to detect perfusion changes in classic perfusion imaging. Conclusions: The presented precision medicine approach using novel biomarkers has the potential to make the application of harmful and complex perfusion methods obsolete

A U-Net Deep Learning Framework for High Performance Vessel Segmentation in Patients With Cerebrovascular Disease

Brain vessel status is a promising biomarker for better prevention and treatment in cerebrovascular disease. However, classic rule-based vessel segmentation algorithms need to be hand-crafted and are insufficiently validated. A specialized deep learning method—the U-net—is a promising alternative. Using labeled data from 66 patients with cerebrovascular disease, the U-net framework was optimized and evaluated with three metrics: Dice coefficient, 95% Hausdorff distance (95HD) and average Hausdorff distance (AVD). The model performance was compared with the traditional segmentation method of graph-cuts. Training and reconstruction was performed using 2D patches. A full and a reduced architecture with less parameters were trained. We performed both quantitative and qualitative analyses. The U-net models yielded high performance for both the full and the reduced architecture: A Dice value of ~0.88, a 95HD of ~47 voxels and an AVD of ~0.4 voxels. The visual analysis revealed excellent performance in large vessels and sufficient performance in small vessels. Pathologies like cortical laminar necrosis and a rete mirabile led to limited segmentation performance in few patients. The U-net outperfomed the traditional graph-cuts method (Dice ~0.76, 95HD ~59, AVD ~1.97). Our work highly encourages the development of clinically applicable segmentation tools based on deep learning. Future works should focus on improved segmentation of small vessels and methodologies to deal with specific pathologies

A U-Net Deep Learning Framework for High Performance Vessel Segmentation in Patients With Cerebrovascular Disease

Brain vessel status is a promising biomarker for better prevention and treatment in cerebrovascular disease. However, classic rule-based vessel segmentation algorithms need to be hand-crafted and are insufficiently validated. A specialized deep learning method-the U-net -is a promising alternative. Using labeled data from 66 patients with cerebrovascular disease, the U-net framework was optimized and evaluated with three metrics: Dice coefficient, 95% Hausdorff distance (95HD) and average Hausdorff distance (AVD). The model performance was compared with the traditional segmentation method of graph-cuts. Training and reconstruction was performed using 2D patches. A full and a reduced architecture with less parameters were trained. We performed both quantitative and qualitative analyses. The U-net models yielded high performance for both the full and the reduced architecture: A Dice value of similar to 0.88, a 95HD of similar to 47 voxels and an AVD of similar to 0.4 voxels. The visual analysis revealed excellent performance in large vessels and sufficient performance in small vessels. Pathologies like cortical laminar necrosis and a rete mirabile led to limited segmentation performance in few patients. The U-net outperfomed the traditional graph-cuts method (Dice similar to 0.76, 95HD similar to 59, AVD similar to 1.97). Our work highly encourages the development of clinically applicable segmentation tools based on deep learning. Future works should focus on improved segmentation of small vessels and methodologies to deal with specific pathologies

A U-Net Deep Learning Framework for High Performance Vessel Segmentation in Paitents with Cerebrovascular Disease

Brain vessel status is a promising biomarker for better prevention and treatment in cerebrovascular disease. However, classic rule-based vessel segmentation algorithms need to be hand-crafted and are insufficiently validated. A specialized deep learning method—the U-net—is a promising alternative. Using labeled data from 66 patients with cerebrovascular disease, the U-net framework was optimized and evaluated with three metrics: Dice coefficient, 95% Hausdorff distance (95HD) and average Hausdorff distance (AVD). The model performance was compared with the traditional segmentation method of graph-cuts. Training and reconstruction was performed using 2D patches. A full and a reduced architecture with less parameters were trained. We performed both quantitative and qualitative analyses. The U-net models yielded high performance for both the full and the reduced architecture: A Dice value of ~0.88, a 95HD of ~47 voxels and an AVD of ~0.4 voxels. The visual analysis revealed excellent performance in large vessels and sufficient performance in small vessels. Pathologies like cortical laminar necrosis and a rete mirabile led to limited segmentation performance in few patients. The U-net outperfomed the traditional graph-cuts method (Dice ~0.76, 95HD ~59, AVD ~1.97). Our work highly encourages the development of clinically applicable segmentation tools based on deep learning. Future works should focus on improved segmentation of small vessels and methodologies to deal with specific pathologie

Comparing Poor and Favorable Outcome Prediction With Machine Learning After Mechanical Thrombectomy in Acute Ischemic Stroke

Outcome prediction after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) is commonly performed by focusing on favorable outcome (modified Rankin Scale, mRS 0–2) after 3 months but poor outcome representing severe disability and mortality (mRS 5 and 6) might be of equal importance for clinical decision-making