Early Identification of Alzheimer’s Disease Using Medical Imaging: A Review From a Machine Learning Approach Perspective

Alzheimer’s disease (AD) is the leading cause of dementia in aged adults, affecting up to 70% of the dementia patients, and posing a serious public health hazard in the twenty-first century. AD is a progressive, irreversible and neuro-degenerative disease with a long pre-clinical period, affecting brain cells leading to memory loss, misperception, learning problems, and improper decisions. Given its significance, presently no treatment options are available, although disease advancement can be retarded through medication. Unfortunately, AD is diagnosed at a very later stage, after irreversible damages to the brain cells have occurred, when there is no scope to prevent further cognitive decline. The use of non-invasive neuroimaging procedures capable of detecting AD at preliminary stages is crucial for providing treatment retarding disease progression, and has stood as a promising area of research. We conducted a comprehensive assessment of papers employing machine learning to predict AD using neuroimaging data. Most of the studies employed brain images from Alzheimer’s disease neuroimaging initiative (ADNI) dataset, consisting of magnetic resonance image (MRI) and positron emission tomography (PET) images. The most widely used method, the support vector machine (SVM), has a mean accuracy of 75.4 percent, whereas convolutional neural networks(CNN) have a mean accuracy of 78.5 percent. Better classification accuracy has been achieved by combining MRI and PET, rather using single neuroimaging technique. Overall, more complicated models, like deep learning, paired with multimodal and multidimensional data (neuroimaging, cognitive, clinical, behavioral and genetic) produced superlative results. However, promising results have been achieved, still there is a room for performance improvement of the proposed methods, providing assistance to healthcare professionals and clinician

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org

Novel Deep Learning Models for Medical Imaging Analysis

abstract: Deep learning is a sub-field of machine learning in which models are developed to imitate the workings of the human brain in processing data and creating patterns for decision making. This dissertation is focused on developing deep learning models for medical imaging analysis of different modalities for different tasks including detection, segmentation and classification. Imaging modalities including digital mammography (DM), magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) are studied in the dissertation for various medical applications. The first phase of the research is to develop a novel shallow-deep convolutional neural network (SD-CNN) model for improved breast cancer diagnosis. This model takes one type of medical image as input and synthesizes different modalities for additional feature sources; both original image and synthetic image are used for feature generation. This proposed architecture is validated in the application of breast cancer diagnosis and proved to be outperforming the competing models. Motivated by the success from the first phase, the second phase focuses on improving medical imaging synthesis performance with advanced deep learning architecture. A new architecture named deep residual inception encoder-decoder network (RIED-Net) is proposed. RIED-Net has the advantages of preserving pixel-level information and cross-modality feature transferring. The applicability of RIED-Net is validated in breast cancer diagnosis and Alzheimer’s disease (AD) staging. Recognizing medical imaging research often has multiples inter-related tasks, namely, detection, segmentation and classification, my third phase of the research is to develop a multi-task deep learning model. Specifically, a feature transfer enabled multi-task deep learning model (FT-MTL-Net) is proposed to transfer high-resolution features from segmentation task to low-resolution feature-based classification task. The application of FT-MTL-Net on breast cancer detection, segmentation and classification using DM images is studied. As a continuing effort on exploring the transfer learning in deep models for medical application, the last phase is to develop a deep learning model for both feature transfer and knowledge from pre-training age prediction task to new domain of Mild cognitive impairment (MCI) to AD conversion prediction task. It is validated in the application of predicting MCI patients’ conversion to AD with 3D MRI images.Dissertation/ThesisDoctoral Dissertation Industrial Engineering 201

Quantitative texture analysis in MR imaging in the assessment of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease which is clinically characterized by cognitive impairment and memory loss. Anatomically, AD initially affects specific structures within the Medial Temporal Lobe (MTL), which are essential for declarative memory. A definitive diagnosis of AD relies on post-mortem biopsy therefore, clinical assessment and cognitive tests are currently used. However, these tests are not sensitive to detect AD in an early stage. The aim of this research was to investigate the usefulness of quantitative Magnetic Resonance Imaging (MRI) and specifically of texture features in the assessment of Mild Cognitive Impairment (MCI) which is the pre-dementia stage and AD. Firstly, two types of magnetic fields where investigated in order to examine whether, a stronger MR magnetic field would benefit quantitative imaging analysis derived from texture features. Secondly, texture features were extracted from the entorhinal cortex and evaluated in the diagnosis and prediction of MCI and AD. To the best of our knowledge this is the first research that investigated how the MR field strength affects texture features and used entorhinal cortex texture features on the assessment of AD. The main results of this PhD showed that (1) texture features could provide more sensitive measures when they are extracted from stronger MRI magnetic field, such as 3T, compared to 1.5T. From a disease classification and prediction perspective, (2) entorhinal cortex texture features provide better classification between Normal Controls (NC), MCI and AD subjects, and (3) better prediction of the conversion from MCI to AD. In conclusion, this research has shown for the first time in the literature that entorhinal cortex texture features from MRI could contribute towards the early classification of AD

Computer aided diagnosis in temporal lobe epilepsy and Alzheimer's dementia

Computer aided diagnosis within neuroimaging must rely on advanced image processing techniques to detect and quantify subtle signal changes that may be surrogate indicators of disease state. This thesis proposes two such novel methodologies that are both based on large volumes of interest, are data driven, and use cross-sectional scans: appearance-based classification (ABC) and voxel-based classification (VBC).The concept of appearance in ABC represents the union of intensity and shape information extracted from magnetic resonance images (MRI). The classification method relies on a linear modeling of appearance features via principal components analysis, and comparison of the distribution of projection coordinates for the populations under study within a reference multidimensional appearance eigenspace. Classification is achieved using forward, stepwise linear discriminant analyses, in multiple cross-validated trials. In this work, the ABC methodology is shown to accurately lateralize the seizure focus in temporal lobe epilepsy (TLE), differentiate normal aging individuals from patients with either Alzheimer's dementia (AD) or Mild Cognitive Impairment (MCI), and finally predict the progression of MCI patients to AD. These applications demonstrated that the ABC technique is robust to different signal changes due to two distinct pathologies, to low resolution data and motion artifacts, and to possible differences inherent to multi-site acquisition.The VBC technique relies on voxel-based morphometry to identify regions of grey and white matter concentration differences between co-registered cohorts of individuals, and then on linear modeling of variables extracted from these regions. Classification is achieved using linear discriminant analyses within a multivariate space composed of voxel-based morphometry measures related to grey and white matter concentration, along with clinical variables of interest. VBC is shown to increase the accuracy of prediction of one-year clinical status from three to four out of five TLE patients having undergone selective amygdalo-hippocampectomy. These two techniques are shown to have the necessary potential to solve current problems in neurological research, assist clinical physicians with their decision-making process and influence positively patient management