With an increase in deep learning-based methods, the call for explainability of such methods grows, especially in high-stakes decision making areas such as medical image analysis. This survey presents an overview of eXplainable Artificial Intelligence (XAI) used in deep learning-based medical image analysis. A framework of XAI criteria is introduced to classify deep learning-based medical image analysis methods. Papers on XAI techniques in medical image analysis are then surveyed and categorized according to the framework and according to anatomical location. The paper concludes with an outlook of future opportunities for XAI in medical image analysis.

Explainable artificial intelligence (XAI) in deep learning-based medical image analysis.

Deep learning models stand for a new learning paradigm in artificial intelligence (AI) and machine learning. Recent breakthrough results in image analysis and speech recognition have generated a massive interest in this field because also applications in many other domains providing big data seem possible. On a downside, the mathematical and computational methodology underlying deep learning models is very challenging, especially for interdisciplinary scientists. For this reason, we present in this paper an introductory review of deep learning approaches including Deep Feedforward Neural Networks (D-FFNN), Convolutional Neural Networks (CNNs), Deep Belief Networks (DBNs), Autoencoders (AEs), and Long Short-Term Memory (LSTM) networks. These models form the major core architectures of deep learning models currently used and should belong in any data scientist's toolbox. Importantly, those core architectural building blocks can be composed flexibly-in an almost Lego-like manner-to build new application-specific network architectures. Hence, a basic understanding of these network architectures is important to be prepared for future developments in AI.

/pdf/an-introductory-review-of-deep-learning-for-prediction-2scaso2g5c.pdf

An Introductory Review of Deep Learning for Prediction Models With Big Data

Purpose: Tumors are continuously evolving biological systems, and medical imaging is uniquely positioned to monitor changes throughout treatment. Although qualitatively tracking lesions over space and time may be trivial, the development of clinically relevant, automated radiomics methods that incorporate serial imaging data is far more challenging. In this study, we evaluated deep learning networks for predicting clinical outcomes through analyzing time series CT images of patients with locally advanced non–small cell lung cancer (NSCLC). Experimental Design: Dataset A consists of 179 patients with stage III NSCLC treated with definitive chemoradiation, with pretreatment and posttreatment CT images at 1, 3, and 6 months follow-up (581 scans). Models were developed using transfer learning of convolutional neural networks (CNN) with recurrent neural networks (RNN), using single seed-point tumor localization. Pathologic response validation was performed on dataset B, comprising 89 patients with NSCLC treated with chemoradiation and surgery (178 scans). Results: Deep learning models using time series scans were significantly predictive of survival and cancer-specific outcomes (progression, distant metastases, and local-regional recurrence). Model performance was enhanced with each additional follow-up scan into the CNN model (e.g., 2-year overall survival: AUC = 0.74, P Conclusions: We demonstrate that deep learning can integrate imaging scans at multiple timepoints to improve clinical outcome predictions. AI-based noninvasive radiomics biomarkers can have a significant impact in the clinic given their low cost and minimal requirements for human input.

/pdf/deep-learning-predicts-lung-cancer-treatment-response-from-2so4nb3lu1.pdf

Deep Learning Predicts Lung Cancer Treatment Response from Serial Medical Imaging

Sensitivity analysis (SA) is en route to becoming an integral part of mathematical modeling. The tremendous potential benefits of SA are, however, yet to be fully realized, both for advancing mechanistic and data-driven modeling of human and natural systems, and in support of decision making. In this perspective paper, a multidisciplinary group of researchers and practitioners revisit the current status of SA, and outline research challenges in regard to both theoretical frameworks and their applications to solve real-world problems. Six areas are discussed that warrant further attention, including (1) structuring and standardizing SA as a discipline, (2) realizing the untapped potential of SA for systems modeling, (3) addressing the computational burden of SA, (4) progressing SA in the context of machine learning, (5) clarifying the relationship and role of SA to uncertainty quantification, and (6) evolving the use of SA in support of decision making. An outlook for the future of SA is provided that underlines how SA must underpin a wide variety of activities to better serve science and society.

The Future of Sensitivity Analysis: An essential discipline for systems modeling and policy support

The successful use of artificial intelligence (AI) for diagnostic purposes has prompted the application of AI-based cancer imaging analysis to address other, more complex, clinical needs. In this Perspective, we discuss the next generation of challenges in clinical decision-making that AI tools can solve using radiology images, such as prognostication of outcome across multiple cancers, prediction of response to various treatment modalities, discrimination of benign treatment confounders from true progression, identification of unusual response patterns and prediction of the mutational and molecular profile of tumours. We describe the evolution of and opportunities for AI in oncology imaging, focusing on hand-crafted radiomic approaches and deep learning-derived representations, with examples of their application for decision support. We also address the challenges faced on the path to clinical adoption, including data curation and annotation, interpretability, and regulatory and reimbursement issues. We hope to demystify AI in radiology for clinicians by helping them to understand its limitations and challenges, as well as the opportunities it provides as a decision-support tool in cancer management.

Predicting cancer outcomes with radiomics and artificial intelligence in radiology.

Background 
Non-small-cell lung cancer (NSCLC) patients often demonstrate varying clinical courses and outcomes, even within the same tumor stage. This study explores deep learning applications in medical imaging allowing for the automated quantification of radiographic characteristics and potentially improving patient stratification.


Methods and findings 
We performed an integrative analysis on 7 independent datasets across 5 institutions totaling 1,194 NSCLC patients (age median = 68.3 years [range 32.5–93.3], survival median = 1.7 years [range 0.0–11.7]). Using external validation in computed tomography (CT) data, we identified prognostic signatures using a 3D convolutional neural network (CNN) for patients treated with radiotherapy (n = 771, age median = 68.0 years [range 32.5–93.3], survival median = 1.3 years [range 0.0–11.7]). We then employed a transfer learning approach to achieve the same for surgery patients (n = 391, age median = 69.1 years [range 37.2–88.0], survival median = 3.1 years [range 0.0–8.8]). We found that the CNN predictions were significantly associated with 2-year overall survival from the start of respective treatment for radiotherapy (area under the receiver operating characteristic curve [AUC] = 0.70 [95% CI 0.63–0.78], p < 0.001) and surgery (AUC = 0.71 [95% CI 0.60–0.82], p < 0.001) patients. The CNN was also able to significantly stratify patients into low and high mortality risk groups in both the radiotherapy (p < 0.001) and surgery (p = 0.03) datasets. Additionally, the CNN was found to significantly outperform random forest models built on clinical parameters—including age, sex, and tumor node metastasis stage—as well as demonstrate high robustness against test–retest (intraclass correlation coefficient = 0.91) and inter-reader (Spearman’s rank-order correlation = 0.88) variations. To gain a better understanding of the characteristics captured by the CNN, we identified regions with the most contribution towards predictions and highlighted the importance of tumor-surrounding tissue in patient stratification. We also present preliminary findings on the biological basis of the captured phenotypes as being linked to cell cycle and transcriptional processes. Limitations include the retrospective nature of this study as well as the opaque black box nature of deep learning networks.


Conclusions 
Our results provide evidence that deep learning networks may be used for mortality risk stratification based on standard-of-care CT images from NSCLC patients. This evidence motivates future research into better deciphering the clinical and biological basis of deep learning networks as well as validation in prospective data.

/pdf/deep-learning-for-lung-cancer-prognostication-a-37k38bveiw.pdf

Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study

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Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study