Explainable, Domain-Adaptive, and Federated Artificial Intelligence in Medicine

Artificial intelligence (AI) continues to transform data analysis in many domains. Progress in each domain is driven by a growing body of annotated data, increased computational resources, and technological innovations. In medicine, the sensitivity of the data, the complexity of the tasks, the potentially high stakes, and a requirement of accountability give rise to a particular set of challenges. In this review, we focus on three key methodological approaches that address some of the particular challenges in AI-driven medical decision making. (1) Explainable AI aims to produce a human-interpretable justification for each output. Such models increase confidence if the results appear plausible and match the clinicians expectations. However, the absence of a plausible explanation does not imply an inaccurate model. Especially in highly non-linear, complex models that are tuned to maximize accuracy, such interpretable representations only reflect a small portion of the justification. (2) Domain adaptation and transfer learning enable AI models to be trained and applied across multiple domains. For example, a classification task based on images acquired on different acquisition hardware. (3) Federated learning enables learning large-scale models without exposing sensitive personal health information. Unlike centralized AI learning, where the centralized learning machine has access to the entire training data, the federated learning process iteratively updates models across multiple sites by exchanging only parameter updates, not personal health data. This narrative review covers the basic concepts, highlights relevant corner-stone and state-of-the-art research in the field, and discusses perspectives.

Gaze Estimation Approach Using Deep Differential Residual Network

Gaze estimation, which is a method to determine where a person is looking at given the person's full face, is a valuable clue for understanding human intention. Similarly to other domains of computer vision, deep learning (DL) methods have gained recognition in the gaze estimation domain. However, there are still gaze calibration problems in the gaze estimation domain, thus preventing existing methods from further improving the performances. An effective solution is to directly predict the difference information of two human eyes, such as the differential network (Diff-Nn). However, this solution results in a loss of accuracy when using only one inference image. We propose a differential residual model (DRNet) combined with a new loss function to make use of the difference information of two eye images. We treat the difference information as auxiliary information. We assess the proposed model (DRNet) mainly using two public datasets (1) MpiiGaze and (2) Eyediap. Considering only the eye features, DRNet outperforms the state-of-the-art gaze estimation methods with $angular-error$ of 4.57 and 6.14 using MpiiGaze and Eyediap datasets, respectively. Furthermore, the experimental results also demonstrate that DRNet is extremely robust to noise images.

Deep radiomic signature with immune cell markers predicts the survival of glioma patients

Imaging biomarkers offer a non-invasive way to predict the response of immunotherapy prior to treatment. In this work, we propose a novel type of deep radiomic features (DRFs) computed from a convolutional neural network (CNN), which capture tumor characteristics related to immune cell markers and overall survival. Our study uses four MRI sequences (T1-weighted, T1-weighted post-contrast, T2-weighted and FLAIR) with corresponding immune cell markers of 151 patients with brain tumor. The proposed method extracts a total of 180 DRFs by aggregating the activation maps of a pre-trained 3D-CNN within labeled tumor regions of MRI scans. These features offer a compact, yet powerful representation of regional texture encoding tissue heterogeneity. A comprehensive set of experiments is performed to assess the relationship between the proposed DRFs and immune cell markers, and measure their association with overall survival. Results show a high correlation between DRFs and various markers, as well as significant differences between patients grouped based on these markers. Moreover, combining DRFs, clinical features and immune cell markers as input to a random forest classifier helps discriminate between short and long survival outcomes, with AUC of 72\% and p=2.36$\times$10$^{-5}$. These results demonstrate the usefulness of proposed DRFs as non-invasive biomarker for predicting treatment response in patients with brain tumors.

Can autism be diagnosed with AI?

Radiomics with deep learning models have become popular in computer-aided diagnosis and have outperformed human experts on many clinical tasks. Specifically, radiomic models based on artificial intelligence (AI) are using medical data (i.e., images, molecular data, clinical variables, etc.) for predicting clinical tasks like Autism Spectrum Disorder (ASD). In this review, we summarized and discussed the radiomic techniques used for ASD analysis. Currently, the limited radiomic work of ASD is related to variation of morphological features of brain thickness that is different from texture analysis. These techniques are based on imaging shape features that can be used with predictive models for predicting ASD. This review explores the progress of ASD-based radiomics with a brief description of ASD and the current non-invasive technique used to classify between ASD and Healthy Control (HC) subjects. With AI, new radiomic models using the deep learning techniques will be also described. To consider the texture analysis with deep CNNs, more investigations are suggested to be integrated with additional validation steps on various MRI sites.

Future Artificial Intelligence tools and perspectives in medicine

Purpose of review: Artificial intelligence (AI) has become popular in medical applications, specifically as a clinical support tool for computer-aided diagnosis. These tools are typically employed on medical data (i.e., image, molecular data, clinical variables, etc.) and used the statistical and machine learning methods to measure the model performance. In this review, we summarized and discussed the most recent radiomic pipeline used for clinical analysis. Recent findings:Currently, limited management of cancers benefits from artificial intelligence, mostly related to a computer-aided diagnosis that avoids a biopsy analysis that presents additional risks and costs. Most AI tools are based on imaging features, known as radiomic analysis that can be refined into predictive models in non-invasively acquired imaging data. This review explores the progress of AI-based radiomic tools for clinical applications with a brief description of necessary technical steps. Explaining new radiomic approaches based on deep learning techniques will explain how the new radiomic models (deep radiomic analysis) can benefit from deep convolutional neural networks and be applied on limited data sets. Summary: To consider the radiomic algorithms, further investigations are recommended to involve deep learning in radiomic models with additional validation steps on various cancer types.

Deep Radiomic Analysis for Predicting Coronavirus Disease 2019 in Computerized Tomography and X-ray Images

This paper proposes to encode the distribution of features learned from a convolutional neural network using a Gaussian Mixture Model. These parametric features, called GMM-CNN, are derived from chest computed tomography and X-ray scans of patients with Coronavirus Disease 2019. We use the proposed GMM-CNN features as input to a robust classifier based on random forests to differentiate between COVID-19 and other pneumonia cases. Our experiments assess the advantage of GMM-CNN features compared to standard CNN classification on test images. Using a random forest classifier (80\% samples for training; 20\% samples for testing), GMM-CNN features encoded with two mixture components provided a significantly better performance than standard CNN classification (p\,$<$\,0.05). Specifically, our method achieved an accuracy in the range of 96.00\,--\,96.70\% and an area under the ROC curve in the range of 99.29\,--\,99.45\%, with the best performance obtained by combining GMM-CNN features from both computed tomography and X-ray images. Our results suggest that the proposed GMM-CNN features could improve the prediction of COVID-19 in chest computed tomography and X-ray scans.

Modeling of Textures to Predict Immune Cell Status and Survival of Brain Tumour Patients

Radiomics has shown a capability for different types of cancers such as glioma to predict the clinical outcome. It can have a non-invasive means of evaluating the immunotherapy response prior to treatment. However, the use of deep convolutional neural networks (CNNs)-based radiomics requires large training image sets. To avoid this problem, we investigate a new imaging features that model distribution with a Gaussian mixture model (GMM) of learned 3D CNN features. Using these deep radiomic features (DRFs), we aim to predict the immune marker status (low versus high) and overall survival for glioma patients. We extract the DRFs by aggregating the activation maps of a pre-trained 3D-CNN within labeled tumor regions of MRI scans that corresponded immune markers of 151 patients. Our experiments are performed to assess the relationship between the proposed DRFs, three immune cell markers (Macrophage M1, Neutrophils and T Cells Follicular Helper), and measure their association with overall survival. Using the random forest (RF) model, DRFs was able to predict the immune marker status with area under the ROC curve (AUC) of 78.67, 83.93 and 75.67\% for Macrophage M1, Neutrophils and T Cells Follicular Helper, respectively. Combined the immune markers with DRFs and clinical variables, Kaplan-Meier estimator and Log-rank test achieved the most significant difference between predicted groups of patients (short-term versus long-term survival) with p\,=\,4.31$\times$10$^{-7}$ compared to p\,=\,0.03 for Immune cell markers, p\,=\,0.07 for clinical variables , and p\,=\,1.45$\times$10$^{-5}$ for DRFs. Our findings indicate that the proposed features (DRFs) used in RF models may significantly consider prognosticating patients with brain tumour prior to surgery through regularly acquired imaging data.

Deep radiomic features from MRI scans predict survival outcome of recurrent glioblastoma

This paper proposes to use deep radiomic features (DRFs) from a convolutional neural network (CNN) to model fine-grained texture signatures in the radiomic analysis of recurrent glioblastoma (rGBM). We use DRFs to predict survival of rGBM patients with preoperative T1-weighted post-contrast MR images (n=100). DRFs are extracted from regions of interest labelled by a radiation oncologist and used to compare between short-term and long-term survival patient groups. Random forest (RF) classification is employed to predict survival outcome (i.e., short or long survival), as well as to identify highly group-informative descriptors. Classification using DRFs results in an area under the ROC curve (AUC) of 89.15% (p<0.01) in predicting rGBM patient survival, compared to 78.07% (p<0.01) when using standard radiomic features (SRF). These results indicate the potential of DRFs as a prognostic marker for patients with rGBM.

Modeling Information Flow Through Deep Neural Networks

This paper proposes a principled information theoretic analysis of classification for deep neural network structures, e.g. convolutional neural networks (CNN). The output of convolutional filters is modeled as a random variable Y conditioned on the object class C and network filter bank F. The conditional entropy (CENT) H(Y |C,F) is shown in theory and experiments to be a highly compact and class-informative code, that can be computed from the filter outputs throughout an existing CNN and used to obtain higher classification results than the original CNN itself. Experiments demonstrate the effectiveness of CENT feature analysis in two separate CNN classification contexts. 1) In the classification of neurodegeneration due to Alzheimer's disease (AD) and natural aging from 3D magnetic resonance image (MRI) volumes, 3 CENT features result in an AUC=94.6% for whole-brain AD classification, the highest reported accuracy on the public OASIS dataset used and 12% higher than the softmax output of the original CNN trained for the task. 2) In the context of visual object classification from 2D photographs, transfer learning based on a small set of CENT features identified throughout an existing CNN leads to AUC values comparable to the 1000-feature softmax output of the original network when classifying previously unseen object categories. The general information theoretical analysis explains various recent CNN design successes, e.g. densely connected CNN architectures, and provides insights for future research directions in deep learning.