Quantifying Differences Between Affine and Nonlinear Spatial Normalization of FP-CIT Spect Images.

Spatial normalization helps us to compare quantitatively two or more input brain scans. Although using an affine normalization approach preserves the anatomical structures, the neuroimaging field is more common to find works that make use of nonlinear transformations. The main reason is that they facilitate a voxel-wise comparison, not only when studying functional images but also when comparing MRI scans given that they fit better to a reference template. However, the amount of bias introduced by the nonlinear transformations can potentially alter the final outcome of a diagnosis especially when studying functional scans for neurological disorders like Parkinson's Disease. In this context, we have tried to quantify the bias introduced by the affine and the nonlinear spatial registration of FP-CIT SPECT volumes of healthy control subjects and patients with PD. For that purpose, we calculated the deformation fields of each participant and applied these deformation fields to a 3D-grid. As the space between the edges of small cubes comprising the grid change, we can quantify which parts from the brain have been enlarged, compressed or just remain the same. When the nonlinear approach is applied, scans from PD patients show a region near their striatum very similar in shape to that of healthy subjects. This artificially increases the interclass separation between patients with PD and healthy subjects as the local intensity is decreased in the latter region, and leads machine learning systems to biased results due to the artificial information introduced by these deformations.

Morphological Characterization of Functional Brain Imaging by Isosurface Analysis in Parkinson's Disease.

Finding new biomarkers to model Parkinson's Disease (PD) is a challenge not only to help discerning between Healthy Control (HC) subjects and patients with potential PD but also as a way to measure quantitatively the loss of dopaminergic neurons mainly concentrated at substantia nigra. Within this context, this work presented here tries to provide a set of imaging features based on morphological characteristics extracted from I[Formula: see text]-Ioflupane SPECT scans to discern between HC and PD participants in a balanced set of [Formula: see text] scans from Parkinson's Progression Markers Initiative (PPMI) database. These features, obtained from isosurfaces of each scan at different intensity levels, have been classified through the use of classical Machine Learning classifiers such as Support-Vector-Machines (SVM) or Naïve Bayesian and compared with the results obtained using a Multi-Layer Perceptron (MLP). The proposed system, based on a Mann-Whitney-Wilcoxon U-Test for feature selection and the SVM approach, yielded a [Formula: see text] balanced accuracy when the performance was evaluated using a [Formula: see text]-fold cross-validation. This proves the reliability of these biomarkers, especially those related to sphericity, center of mass, number of vertices, 2D-projected perimeter or the 2D-projected eccentricity, among others, but including both internal and external isosurfaces.

Autosomal Dominantly Inherited Alzheimer Disease: Analysis of genetic subgroups by Machine Learning.

Despite subjects with Dominantly-Inherited Alzheimer's Disease (DIAD) represent less than 1% of all Alzheimer's Disease (AD) cases, the Dominantly Inherited Alzheimer Network (DIAN) initiative constitutes a strong impact in the understanding of AD disease course with special emphasis on the presyptomatic disease phase. Until now, the 3 genes involved in DIAD pathogenesis (PSEN1, PSEN2 and APP) have been commonly merged into one group (Mutation Carriers, MC) and studied using conventional statistical analysis. Comparisons between groups using null-hypothesis testing or longitudinal regression procedures, such as the linear-mixed-effects models, have been assessed in the extant literature. Within this context, the work presented here performs a comparison between different groups of subjects by considering the 3 genes, either jointly or separately, and using tools based on Machine Learning (ML). This involves a feature selection step which makes use of ANOVA followed by Principal Component Analysis (PCA) to determine which features would be realiable for further comparison purposes. Then, the selected predictors are classified using a Support-Vector-Machine (SVM) in a nested k-Fold cross-validation resulting in maximum classification rates of 72-74% using PiB PET features, specially when comparing asymptomatic Non-Carriers (NC) subjects with asymptomatic PSEN1 Mutation-Carriers (PSEN1-MC). Results obtained from these experiments led to the idea that PSEN1-MC might be considered as a mixture of two different subgroups including: a first group whose patterns were very close to NC subjects, and a second group much more different in terms of imaging patterns. Thus, using a k-Means clustering algorithm it was determined both subgroups and a new classification scenario was conducted to validate this process. The comparison between each subgroup vs. NC subjects resulted in classification rates around 80% underscoring the importance of considering DIAN as an heterogeneous entity.

Parkinson's Disease Detection Using Isosurfaces-Based Features and Convolutional Neural Networks.

Computer aided diagnosis systems based on brain imaging are an important tool to assist in the diagnosis of Parkinson's disease, whose ultimate goal is the detection by automatic recognizing of patterns that characterize the disease. In recent times Convolutional Neural Networks (CNN) have proved to be amazingly useful for that task. The drawback, however, is that 3D brain images contain a huge amount of information that leads to complex CNN architectures. When these architectures become too complex, classification performances often degrades because the limitations of the training algorithm and overfitting. Thus, this paper proposes the use of isosurfaces as a way to reduce such amount of data while keeping the most relevant information. These isosurfaces are then used to implement a classification system which uses two of the most well-known CNN architectures, LeNet and AlexNet, to classify DaTScan images with an average accuracy of 95.1% and AUC = 97%, obtaining comparable (slightly better) values to those obtained for most of the recently proposed systems. It can be concluded therefore that the computation of isosurfaces reduces the complexity of the inputs significantly, resulting in high classification accuracies with reduced computational burden.

Robust Ensemble Classification Methodology for I123-Ioflupane SPECT Images and Multiple Heterogeneous Biomarkers in the Diagnosis of Parkinson's Disease.

In last years, several approaches to develop an effective Computer-Aided-Diagnosis (CAD) system for Parkinson's Disease (PD) have been proposed. Most of these methods have focused almost exclusively on brain images through the use of Machine-Learning algorithms suitable to characterize structural or functional patterns. Those patterns provide enough information about the status and/or the progression at intermediate and advanced stages of Parkinson's Disease. Nevertheless this information could be insufficient at early stages of the pathology. The Parkinson's Progression Markers Initiative (PPMI) database includes neurological images along with multiple biomedical tests. This information opens up the possibility of comparing different biomarker classification results. As data come from heterogeneous sources, it is expected that we could include some of these biomarkers in order to obtain new information about the pathology. Based on that idea, this work presents an Ensemble Classification model with Performance Weighting. This proposal has been tested comparing Healthy Control subjects (HC) vs. patients with PD (considering both PD and SWEDD labeled subjects as the same class). This model combines several Support-Vector-Machine (SVM) with linear kernel classifiers for different biomedical group of tests-including CerebroSpinal Fluid (CSF), RNA, and Serum tests-and pre-processed neuroimages features (Voxels-As-Features and a list of defined Morphological Features) from PPMI database subjects. The proposed methodology makes use of all data sources and selects the most discriminant features (mainly from neuroimages). Using this performance-weighted ensemble classification model, classification results up to 96% were obtained.

A Heavy Tailed Expectation Maximization Hidden Markov Random Field Model with Applications to Segmentation of MRI.

A wide range of segmentation approaches assumes that intensity histograms extracted from magnetic resonance images (MRI) have a distribution for each brain tissue that can be modeled by a Gaussian distribution or a mixture of them. Nevertheless, intensity histograms of White Matter and Gray Matter are not symmetric and they exhibit heavy tails. In this work, we present a hidden Markov random field model with expectation maximization (EM-HMRF) modeling the components using the α-stable distribution. The proposed model is a generalization of the widely used EM-HMRF algorithm with Gaussian distributions. We test the α-stable EM-HMRF model in synthetic data and brain MRI data. The proposed methodology presents two main advantages: Firstly, it is more robust to outliers. Secondly, we obtain similar results than using Gaussian when the Gaussian assumption holds. This approach is able to model the spatial dependence between neighboring voxels in tomographic brain MRI.

Functional Brain Imaging Synthesis Based on Image Decomposition and Kernel Modeling: Application to Neurodegenerative Diseases.

The rise of neuroimaging in research and clinical practice, together with the development of new machine learning techniques has strongly encouraged the Computer Aided Diagnosis (CAD) of different diseases and disorders. However, these algorithms are often tested in proprietary datasets to which the access is limited and, therefore, a direct comparison between CAD procedures is not possible. Furthermore, the sample size is often small for developing accurate machine learning methods. Multi-center initiatives are currently a very useful, although limited, tool in the recruitment of large populations and standardization of CAD evaluation. Conversely, we propose a brain image synthesis procedure intended to generate a new image set that share characteristics with an original one. Our system focuses on nuclear imaging modalities such as PET or SPECT brain images. We analyze the dataset by applying PCA to the original dataset, and then model the distribution of samples in the projected eigenbrain space using a Probability Density Function (PDF) estimator. Once the model has been built, we can generate new coordinates on the eigenbrain space belonging to the same class, which can be then projected back to the image space. The system has been evaluated on different functional neuroimaging datasets assessing the: resemblance of the synthetic images with the original ones, the differences between them, their generalization ability and the independence of the synthetic dataset with respect to the original. The synthetic images maintain the differences between groups found at the original dataset, with no significant differences when comparing them to real-world samples. Furthermore, they featured a similar performance and generalization capability to that of the original dataset. These results prove that these images are suitable for standardizing the evaluation of CAD pipelines, and providing data augmentation in machine learning systems -e.g. in deep learning-, or even to train future professionals at medical school.

Preprocessing of 18F-DMFP-PET Data Based on Hidden Markov Random Fields and the Gaussian Distribution.

18F-DMFP-PET is an emerging neuroimaging modality used to diagnose Parkinson's disease (PD) that allows us to examine postsynaptic dopamine D2/3 receptors. Like other neuroimaging modalities used for PD diagnosis, most of the total intensity of 18F-DMFP-PET images is concentrated in the striatum. However, other regions can also be useful for diagnostic purposes. An appropriate delimitation of the regions of interest contained in 18F-DMFP-PET data is crucial to improve the automatic diagnosis of PD. In this manuscript we propose a novel methodology to preprocess 18F-DMFP-PET data that improves the accuracy of computer aided diagnosis systems for PD. First, the data were segmented using an algorithm based on Hidden Markov Random Field. As a result, each neuroimage was divided into 4 maps according to the intensity and the neighborhood of the voxels. The maps were then individually normalized so that the shape of their histograms could be modeled by a Gaussian distribution with equal parameters for all the neuroimages. This approach was evaluated using a dataset with neuroimaging data from 87 parkinsonian patients. After these preprocessing steps, a Support Vector Machine classifier was used to separate idiopathic and non-idiopathic PD. Data preprocessed by the proposed method provided higher accuracy results than the ones preprocessed with previous approaches.

Statistical significance in the selection of the regions of interest for Parkinson brain image processing.

This paper presents the analysis of the statistical significance in the selection of the ROI for the discriminant analysis of brain images to identify Parkinson patients or subjects without any pathology. The particular features and brain functional patterns of the Parkinson's disease cause that there are regions that conveniently reveal the presence of the pathology, in this case mainly the striatum region. The selection of the brain mask makes incidence in two main aspects: the selection of the region of interest (striatum and surrounding area) for the analysis, but also the selection of the region without significance, which is the reference area for the intensity normalization, previous to the analysis. This work studies the statistical significance in the selection of ROIs in 3D brain images for Parkinson, depending on the objective to be achieved in the posterior analysis process.

Affine registration of [123I]FP-CIT SPECT brain images.

In this work, we perform a comparison between the spatial normalization of [123I]FP-CIT SPECT brain images when a FP-CIT SPECT and a MRI template are used. A 12-parameters affine registration model is calculated by the optimization of a sum of squares cost function. When the images are registered to a FP-CIT template, the intersubject variation is found to be lower than when the MRI template is used, specially in the striatum, which is the most relevant part of the brain in FP-CIT SPECT brain images.

Projecting MRI brain images for the detection of Alzheimer's Disease.

Recent advances in the process of diagnosis of neurodegenerative diseases, such as Alzheimer's Disease, rely on the use of molecular imaging that allow the interpretation of different metabolic biomarkers in the brain. However these procedures are considered of invasive nature, as they involve the injection of radioactive markers. On the other hand, Magnetic Resonance Imaging (MRI) is perhaps the most widely used and less invasive medical imaging technique, although its ability to detect Alzheimer's Disease has revealed limited. In this paper, a new method that simplifies the process of analysing 3D MRI brain images using a two dimensional projection is proposed. Our system outperforms other methods that use MRI, achieving up to a 86% of accuracy and significantly reducing the computational load. Additionally, it allows the visual analysis and interpretation of the images, which can be of great help in the diagnosis of this and other types of dementia.

Segmentation of brain MRI using SOM-FCM-based method and 3D statistical descriptors.

Current medical imaging systems provide excellent spatial resolution, high tissue contrast, and up to 65535 intensity levels. Thus, image processing techniques which aim to exploit the information contained in the images are necessary for using these images in computer-aided diagnosis (CAD) systems. Image segmentation may be defined as the process of parcelling the image to delimit different neuroanatomical tissues present on the brain. In this paper we propose a segmentation technique using 3D statistical features extracted from the volume image. In addition, the presented method is based on unsupervised vector quantization and fuzzy clustering techniques and does not use any a priori information. The resulting fuzzy segmentation method addresses the problem of partial volume effect (PVE) and has been assessed using real brain images from the Internet Brain Image Repository (IBSR).

Linear intensity normalization of FP-CIT SPECT brain images using the α-stable distribution.

In this work, a linear procedure to perform the intensity normalization of FP-CIT SPECT brain images is presented. This proposed methodology is based on the fact that the histogram of intensity values can be fitted accurately using a positive skewed α-stable distribution. Then, the predicted α-stable parameters and the location-scale property are used to linearly transform the intensity values in each voxel. This transformation is performed such that the new histograms in each image have a pre-specified α-stable distribution with desired location and dispersion values. The proposed methodology is compared with a similar approach assuming Gaussian distribution and the widely used specific-to-nonspecific ratio. In this work, we show that the linear normalization method using the α-stable distribution outperforms those existing methods.

Bilateral symmetry aspects in computer-aided Alzheimer's disease diagnosis by single-photon emission-computed tomography imaging.

OBJECTIVE: This paper explores the importance of the latent symmetry of the brain in computer-aided systems for diagnosing Alzheimer's disease (AD). Symmetry and asymmetry are studied from two points of view: (i) the development of an effective classifier within the scope of machine learning techniques, and (ii) the assessment of its relevance to the AD diagnosis in the early stages of the disease. METHODS: The proposed methodology is based on eigenimage decomposition of single-photon emission-computed tomography images, using an eigenspace extension to accommodate odd and even eigenvectors separately. This feature extraction technique allows for support-vector-machine classification and image analysis. RESULTS: Identification of AD patterns is improved when the latent symmetry of the brain is considered, with an estimated 92.78% accuracy (92.86% sensitivity, 92.68% specificity) using a linear kernel and a leave-one-out cross validation strategy. Also, asymmetries may be used to define a test for AD that is very specific (90.24% specificity) but not especially sensitive. CONCLUSIONS: Two main conclusions are derived from the analysis of the eigenimage spectrum. Firstly, the recognition of AD patterns is improved when considering only the symmetric part of the spectrum. Secondly, asymmetries in the hypo-metabolic patterns, when present, are more pronounced in subjects with AD.

Analysis of SPECT brain images for the diagnosis of Alzheimer's disease using moments and support vector machines.

This paper presents a computer-aided diagnosis technique for improving the accuracy of diagnosing the Alzheimer's type dementia. The proposed methodology is based on the calculation of the skewness for each m-by-m-by-m sliding block of the SPECT brain images. The center pixel in this m-by-m-by-m block is replaced by the skewness value to build a new 3-D brain image which is used for classification purposes. After that, voxels which present a Welch's t-statistic between classes, Normal and Alzheimer's images, higher (or lower) than a threshold are selected. The mean, standard deviation, skewness and kurtosis are calculated for these selected voxels and they are subjected as features to linear kernel based support vector machine classifier. The proposed methodology reaches accuracy higher than 99% in the classification task.