Visualizing Convolutional Networks for MRI-based Diagnosis of Alzheimer's Disease

Visualizing and interpreting convolutional neural networks (CNNs) is an important task to increase trust in automatic medical decision making systems. In this study, we train a 3D CNN to detect Alzheimer's disease based on structural MRI scans of the brain. Then, we apply four different gradient-based and occlusion-based visualization methods that explain the network's classification decisions by highlighting relevant areas in the input image. We compare the methods qualitatively and quantitatively. We find that all four methods focus on brain regions known to be involved in Alzheimer's disease, such as inferior and middle temporal gyrus. While the occlusion-based methods focus more on specific regions, the gradient-based methods pick up distributed relevance patterns. Additionally, we find that the distribution of relevance varies across patients, with some having a stronger focus on the temporal lobe, whereas for others more cortical areas are relevant. In summary, we show that applying different visualization methods is important to understand the decisions of a CNN, a step that is crucial to increase clinical impact and trust in computer-based decision support systems.Comment: MLCN 201

Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: Evaluation in Alzheimer's disease

Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$\geq$0.92) and moderate accuracy for MCI vs. controls (AUC$\approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r$\approx$-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels.Comment: 24 pages, 9 figures/tables, supplementary material, source code available on GitHu

Towards Practical Application of Deep Learning in Diagnosis of Alzheimer's Disease

Accurate diagnosis of Alzheimer's disease (AD) is both challenging and time consuming. With a systematic approach for early detection and diagnosis of AD, steps can be taken towards the treatment and prevention of the disease. This study explores the practical application of deep learning models for diagnosis of AD. Due to computational complexity, large training times and limited availability of labelled dataset, a 3D full brain CNN (convolutional neural network) is not commonly used, and researchers often prefer 2D CNN variants. In this study, full brain 3D version of well-known 2D CNNs were designed, trained and tested for diagnosis of various stages of AD. Deep learning approach shows good performance in differentiating various stages of AD for more than 1500 full brain volumes. Along with classification, the deep learning model is capable of extracting features which are key in differentiating the various categories. The extracted features align with meaningful anatomical landmarks, that are currently considered important in identification of AD by experts. An ensemble of all the algorithm was also tested and the performance of the ensemble algorithm was superior to any individual algorithm, further improving diagnosis ability. The 3D versions of the trained CNNs and their ensemble have the potential to be incorporated in software packages that can be used by physicians/radiologists to assist them in better diagnosis of AD.Comment: 18 pages, 8 figure

Diagnosis and monitoring of Alzheimer's patients using classical and deep learning techniques

Machine based analysis and prediction systems are widely used for diagnosis of Alzheimer's Disease (AD). However, lower accuracy of existing techniques and lack of post diagnosis monitoring systems limit the scope of such studies. In this paper, a novel machine learning based diagnosis and monitoring of AD-like diseases is proposed. The AD-like diseases diagnosis process is accomplished by analysing the magnetic resonance imaging (MRI) scans using deep learning and is followed by an activity monitoring framework to monitor the subjects’ activities of daily living using body worn inertial sensors. The activity monitoring provides an assistive framework in daily life activities and evaluates vulnerability of the patients based on the activity level. The AD diagnosis results show up to 82% improvement in comparison to well-known existing techniques. Moreover, above 95% accuracy is achieved to classify the activities of daily living which is quite encouraging in terms of monitoring the activity profile of the subject

Explainable deep learning classifiers for disease detection based on structural brain MRI data

In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those

Diagnosis and monitoring of Alzheimer's patients using classical and deep learning techniques

Machine based analysis and prediction systems are widely used for diagnosis of Alzheimer's Disease (AD). However, lower accuracy of existing techniques and lack of post diagnosis monitoring systems limit the scope of such studies. In this paper, a novel machine learning based diagnosis and monitoring of AD-like diseases is proposed. The AD-like diseases diagnosis process is accomplished by analysing the magnetic resonance imaging (MRI) scans using deep learning and is followed by an activity monitoring framework to monitor the subjects’ activities of daily living using body worn inertial sensors. The activity monitoring provides an assistive framework in daily life activities and evaluates vulnerability of the patients based on the activity level. The AD diagnosis results show up to 82% improvement in comparison to well-known existing techniques. Moreover, above 95% accuracy is achieved to classify the activities of daily living which is quite encouraging in terms of monitoring the activity profile of the subject

Detecting Alzheimer\u27s Disease using Artificial Neural Networks

This project aims to use artificial neural networks (ANN) in order to detect Alzheimer’s disease. More specifically, convolutional neural networks (CNN) will be utilized as this is the most common ANN and has been used in many different image processing applications. The purpose of using artificial neural networks as a detect method is so that an intelligent way for image and signal analysis can be used. A software that implements CNN will be developed so that users in medical settings can utilize this software to detect Alzheimer’s in patients. The input for this software will be the patient’s MRI scans. In addition, this is a project that is relevant with the current trends of an increase in development surrounding artificial intelligence. As technology has become more advanced, there has been an increase in medical developments as well. From the simulation, the hyperbolic tangent activation function provided the best results. The performance resulting from the two classifications when using the hyperbolic tangent function, on average was validation best accuracy of 81.10%, validation stopped tuning accuracy of 81.10%, training best accuracy of 100.00%, testing best accuracy of 68.94%, F-1 score of 70.06%, precision of 71.00%, and recall of 70.06%. This project will open doors to more applications of this detection method. More diseases other than Alzheimer’s disease can utilize artificial neural networks (ANN) to detect diseases early on so that lives can be restored and saved

Machine Learning for Multiclass Classification and Prediction of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is an irreversible neurodegenerative disorder and a common form of dementia. This research aims to develop machine learning algorithms that diagnose and predict the progression of AD from multimodal heterogonous biomarkers with a focus placed on the early diagnosis. To meet this goal, several machine learning-based methods with their unique characteristics for feature extraction and automated classification, prediction, and visualization have been developed to discern subtle progression trends and predict the trajectory of disease progression. The methodology envisioned aims to enhance both the multiclass classification accuracy and prediction outcomes by effectively modeling the interplay between the multimodal biomarkers, handle the missing data challenge, and adequately extract all the relevant features that will be fed into the machine learning framework, all in order to understand the subtle changes that happen in the different stages of the disease. This research will also investigate the notion of multitasking to discover how the two processes of multiclass classification and prediction relate to one another in terms of the features they share and whether they could learn from one another for optimizing multiclass classification and prediction accuracy. This research work also delves into predicting cognitive scores of specific tests over time, using multimodal longitudinal data. The intent is to augment our prospects for analyzing the interplay between the different multimodal features used in the input space to the predicted cognitive scores. Moreover, the power of modality fusion, kernelization, and tensorization have also been investigated to efficiently extract important features hidden in the lower-dimensional feature space without being distracted by those deemed as irrelevant. With the adage that a picture is worth a thousand words, this dissertation introduces a unique color-coded visualization system with a fully integrated machine learning model for the enhanced diagnosis and prognosis of Alzheimer\u27s disease. The incentive here is to show that through visualization, the challenges imposed by both the variability and interrelatedness of the multimodal features could be overcome. Ultimately, this form of visualization via machine learning informs on the challenges faced with multiclass classification and adds insight into the decision-making process for a diagnosis and prognosis