Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes

BACKGROUND: We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. METHODS: Clinical information and brain MRIs were collected from 221 healthy individuals and 823 people with MS at 8 MAGNIMS centres. The patients were divided into four clinical phenotypes: clinically isolated syndrome, relapsing-remitting, secondary progressive and primary progressive. Advanced tractography methods were used to obtain connectivity matrices. Then, differences in whole-brain and nodal graph-derived measures, and in the fractional anisotropy of connections between groups were analysed. Support vector machine algorithms were used to classify groups. RESULTS: Clinically isolated syndrome and relapsing-remitting patients shared similar network changes relative to controls. However, most global and local network properties differed in secondary progressive patients compared with the other groups, with lower fractional anisotropy in most connections. Primary progressive participants had fewer differences in global and local graph measures compared with clinically isolated syndrome and relapsing-remitting patients, and reductions in fractional anisotropy were only evident for a few connections. The accuracy of support vector machine to discriminate patients from healthy controls based on connection was 81%, and ranged between 64% and 74% in distinguishing among the clinical phenotypes. CONCLUSIONS: In conclusion, brain connectivity is disrupted in MS and has differential patterns according to the phenotype. Secondary progressive is associated with more widespread changes in connectivity. Additionally, classification tasks can distinguish between MS types, with subcortical connections being the most important factor

Considering patient clinical history impacts performance of machine learning models in predicting course of multiple sclerosis

Multiple Sclerosis (MS) progresses at an unpredictable rate, but predictions on the disease course in each patient would be extremely useful to tailor therapy to the individual needs. We explore different machine learning (ML) approaches to predict whether a patient will shift from the initial Relapsing-Remitting (RR) to the Secondary Progressive (SP) form of the disease, using only “real world” data available in clinical routine. The clinical records of 1624 outpatients (207 in the SP phase) attending the MS service of Sant'Andrea hospital, Rome, Italy, were used. Predictions at 180, 360 or 720 days from the last visit were obtained considering either the data of the last available visit (Visit-Oriented setting), comparing four classical ML methods (Random Forest, Support Vector Machine, K-Nearest Neighbours and AdaBoost) or the whole clinical history of each patient (History-Oriented setting), using a Recurrent Neural Network model, specifically designed for historical data. Missing values were handled by removing either all clinical records presenting at least one missing parameter (Feature-saving approach) or the 3 clinical parameters which contained missing values (Record-saving approach). The performances of the classifiers were rated using common indicators, such as Recall (or Sensitivity) and Precision (or Positive predictive value). In the visit-oriented setting, the Record-saving approach yielded Recall values from 70% to 100%, but low Precision (5% to 10%), which however increased to 50% when considering only predictions for which the model returned a probability above a given “confidence threshold”. For the History-oriented setting, both indicators increased as prediction time lengthened, reaching values of 67% (Recall) and 42% (Precision) at 720 days. We show how “real world” data can be effectively used to forecast the evolution of MS, leading to high Recall values and propose innovative approaches to improve Precision towards clinically useful values

Investigating Brain Functional Networks in a Riemannian Framework

The brain is a complex system of several interconnected components which can be categorized at different Spatio-temporal levels, evaluate the physical connections and the corresponding functionalities. To study brain connectivity at the macroscale, Magnetic Resonance Imaging (MRI) technique in all the different modalities has been exemplified to be an important tool. In particular, functional MRI (fMRI) enables to record the brain activity either at rest or in different conditions of cognitive task and assist in mapping the functional connectivity of the brain. The information of brain functional connectivity extracted from fMRI images can be defined using a graph representation, i.e. a mathematical object consisting of nodes, the brain regions, and edges, the link between regions. With this representation, novel insights have emerged about understanding brain connectivity and providing evidence that the brain networks are not randomly linked. Indeed, the brain network represents a small-world structure, with several different properties of segregation and integration that are accountable for specific functions and mental conditions. Moreover, network analysis enables to recognize and analyze patterns of brain functional connectivity characterizing a group of subjects. In recent decades, many developments have been made to understand the functioning of the human brain and many issues, related to the biological and the methodological perspective, are still need to be addressed. For example, sub-modular brain organization is still under debate, since it is necessary to understand how the brain is functionally organized. At the same time a comprehensive organization of functional connectivity is mostly unknown and also the dynamical reorganization of functional connectivity is appearing as a new frontier for analyzing brain dynamics. Moreover, the recognition of functional connectivity patterns in patients affected by mental disorders is still a challenging task, making plausible the development of new tools to solve them. Indeed, in this dissertation, we proposed novel methodological approaches to answer some of these biological and neuroscientific questions. We have investigated methods for analyzing and detecting heritability in twin's task-induced functional connectivity profiles. in this approach we are proposing a geodesic metric-based method for the estimation of similarity between functional connectivity, taking into account the manifold related properties of symmetric and positive definite matrices. Moreover, we also proposed a computational framework for classification and discrimination of brain connectivity graphs between healthy and pathological subjects affected by mental disorder, using geodesic metric-based clustering of brain graphs on manifold space. Within the same framework, we also propose an approach based on the dictionary learning method to encode the high dimensional connectivity data into a vectorial representation which is useful for classification and determining regions of brain graphs responsible for this segregation. We also propose an effective way to analyze the dynamical functional connectivity, building a similarity representation of fMRI dynamic functional connectivity states, exploiting modular properties of graph laplacians, geodesic clustering, and manifold learning

Computer-aided diagnosis of multiple sclerosis using a support vector machine and optical coherence tomography features

The purpose of this paper is to evaluate the feasibility of diagnosing multiple sclerosis (MS) using optical coherence tomography (OCT) data and a support vector machine (SVM) as an automatic classifier. Forty-eight MS patients without symptoms of optic neuritis and forty-eight healthy control subjects were selected. Swept-source optical coherence tomography (SS-OCT) was performed using a DRI (deep-range imaging) Triton OCT device (Topcon Corp., Tokyo, Japan). Mean values (right and left eye) for macular thickness (retinal and choroidal layers) and peripapillary area (retinal nerve fibre layer, retinal, ganglion cell layer—GCL, and choroidal layers) were compared between both groups. Based on the analysis of the area under the receiver operator characteristic curve (AUC), the 3 variables with the greatest discriminant capacity were selected to form the feature vector. A SVM was used as an automatic classifier, obtaining the confusion matrix using leave-one-out cross-validation. Classification performance was assessed with Matthew’s correlation coefficient (MCC) and the AUCCLASSIFIER. The most discriminant variables were found to be the total GCL++ thickness (between inner limiting membrane to inner nuclear layer boundaries), evaluated in the peripapillary area and macular retina thickness in the nasal quadrant of the outer and inner rings. Using the SVM classifier, we obtained the following values: MCC = 0.81, sensitivity = 0.89, specificity = 0.92, accuracy = 0.91, and AUCCLASSIFIER = 0.97. Our findings suggest that it is possible to classify control subjects and MS patients without previous optic neuritis by applying machine-learning techniques to study the structural neurodegeneration in the retina

A computer-aided diagnosis of multiple sclerosis based on mfVEP recordings.

Introduction: The aim of this study is to develop a computer-aided diagnosis system to identify subjects at differing stages of development of multiple sclerosis (MS) using multifocal visual-evoked potentials (mfVEPs). Using an automatic classifier, diagnosis is performed first on the eyes and then on the subjects. Patients: MfVEP signals were obtained from patients with Radiologically Isolated Syndrome (RIS) (n = 30 eyes), patients with Clinically Isolated Syndrome (CIS) (n = 62 eyes), patients with definite MS (n = 56 eyes) and 22 control subjects (n = 44 eyes). The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON). Methods: For individual eye diagnosis, a feature vector was formed with information about the intensity, latency and singular values of the mfVEP signals. A flat multiclass classifier (FMC) and a hierarchical classifier (HC) were tested and both were implemented using the k-Nearest Neighbour (k-NN) algorithm. The output of the best eye classifier was used to classify the subjects. In the event of divergence, the eye with the best mfVEP recording was selected. Results: In the eye classifier, the HC performed better than the FMC (accuracy = 0.74 and extended Matthew Correlation Coefficient (MCC) = 0.68). In the subject classification, accuracy = 0.95 and MCC = 0.93, confirming that it may be a promising tool for MS diagnosis. Chirped-pulse φOTDR provides distributed strain measurement via a time-delay estimation process. We propose a lower bound for performance, after reducing sampling error and compensating phase-noise. We attempt to reach the limit, attaining unprecedented pε/√Hz sensitivities. Conclusion: In addition to amplitude (axonal loss) and latency (demyelination), it has shown that the singular values of the mfVEP signals provide discriminatory information that may be used to identify subjects with differing degrees of the disease.Secretaría de Estado de Investigación, Desarrollo e InnovaciónInstituto de Salud Carlos II

Challenges in biomedical data science: data-driven solutions to clinical questions

Data are influencing every aspect of our lives, from our work activities, to our spare time and even to our health. In this regard, medical diagnosis and treatments are often supported by quantitative measures and observations, such as laboratory tests, medical imaging or genetic analysis. In medicine, as well as in several other scientific domains, the amount of data involved in each decision-making process has become overwhelming. The complexity of the phenomena under investigation and the scale of modern data collections has long superseded human analysis and insights potential