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

Explainable artificial intelligence toward usable and trustworthy computer-aided early diagnosis of multiple sclerosis from Optical Coherence Tomography

Background: Several studies indicate that the anterior visual pathway provides information about the dynamics of axonal degeneration in Multiple Sclerosis (MS). Current research in the field is focused on the quest for the most discriminative features among patients and controls and the development of machine learning models that yield computer-aided solutions widely usable in clinical practice. However, most studies are conducted with small samples and the models are used as black boxes. Clinicians should not trust machine learning decisions unless they come with comprehensive and easily understandable explanations. Materials and methods: A total of 216 eyes from 111 healthy controls and 100 eyes from 59 patients with relapsing-remitting MS were enrolled. The feature set was obtained from the thickness of the ganglion cell layer (GCL) and the retinal nerve fiber layer (RNFL). Measurements were acquired by the novel Posterior Pole protocol from Spectralis Optical Coherence Tomography (OCT) device. We compared two black-box methods (gradient boosting and random forests) with a glass-box method (explainable boosting machine). Explainability was studied using SHAP for the black-box methods and the scores of the glass-box method. Results: The best-performing models were obtained for the GCL layer. Explainability pointed out to the temporal location of the GCL layer that is usually broken or thinning in MS and the relationship between low thickness values and high probability of MS, which is coherent with clinical knowledge. Conclusions: The insights on how to use explainability shown in this work represent a first important step toward a trustworthy computer-aided solution for the diagnosis of MS with OCT

Explainable artificial intelligence toward usable and trustworthy computer-aided diagnosis of multiple sclerosis from Optical Coherence Tomography

Background: Several studies indicate that the anterior visual pathway provides information about the dynamics of axonal degeneration in Multiple Sclerosis (MS). Current research in the field is focused on the quest for the most discriminative features among patients and controls and the development of machine learning models that yield computer-aided solutions widely usable in clinical practice. However, most studies are conducted with small samples and the models are used as black boxes. Clinicians should not trust machine learning decisions unless they come with comprehensive and easily understandable explanations. Materials and methods: A total of 216 eyes from 111 healthy controls and 100 eyes from 59 patients with relapsing-remitting MS were enrolled. The feature set was obtained from the thickness of the ganglion cell layer (GCL) and the retinal nerve fiber layer (RNFL). Measurements were acquired by the novel Posterior Pole protocol from Spectralis Optical Coherence Tomography (OCT) device. We compared two black-box methods (gradient boosting and random forests) with a glass-box method (explainable boosting machine). Explainability was studied using SHAP for the black-box methods and the scores of the glass-box method. Results: The best-performing models were obtained for the GCL layer. Explainability pointed out to the temporal location of the GCL layer that is usually broken or thinning in MS and the relationship between low thickness values and high probability of MS, which is coherent with clinical knowledge.Conclusions: The insights on how to use explainability shown in this work represent a first important step toward a trustworthy computer-aided solution for the diagnosis of MS with OCT

The macular retinal ganglion cell layer as a biomarker for diagnosis and prognosis in multiple sclerosis: A deep learning approach

AbstractPurposeThe macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer‐aided method to facilitate diagnosis and prognosis in MS.MethodsThis paper combines a cross‐sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10‐year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier.ResultsFor MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs.ConclusionWe present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non‐invasive, low‐cost, easy‐to‐implement and effective method

Diagnosis of multiple sclerosis using multifocal ERG data feature fusion

The purpose of this paper is to implement a computer-aided diagnosis (CAD) system for multiple sclerosis (MS) based on analysing the outer retina as assessed by multifocal electroretinograms (mfERGs). MfERG recordings taken with the RETI?port/scan 21 (Roland Consult) device from 15 eyes of patients diagnosed with incipient relapsing-remitting MS and without prior optic neuritis, and from 6 eyes of control subjects, are selected. The mfERG recordings are grouped (whole macular visual field, five rings, and four quadrants). For each group, the correlation with a normative database of adaptively filtered signals, based on empirical model decomposition (EMD) and three features from the continuous wavelet transform (CWT) domain, are obtained. Of the initial 40 features, the 4 most relevant are selected in two stages: a) using a filter method and b) using a wrapper-feature selection method. The Support Vector Machine (SVM) is used as a classifier. With the optimal CAD configuration, a Matthews correlation coefficient value of 0.89 (accuracy = 0.95, specificity = 1.0 and sensitivity = 0.93) is obtained. This study identified an outer retina dysfunction in patients with recent MS by analysing the outer retina responses in the mfERG and employing an SVM as a classifier. In conclusion, a promising new electrophysiological-biomarker method based on feature fusion for MS diagnosis was identified.Agencia Estatal de InvestigaciónInstituto de Salud Carlos II

Comparison of Machine Learning Methods Using Spectralis OCT for Diagnosis and Disability Progression Prognosis in Multiple Sclerosis

Machine learning approaches in diagnosis and prognosis of multiple sclerosis (MS) were analysed using retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT). A cross-sectional study (72 MS patients and 30 healthy controls) was used for diagnosis. These 72 MS patients were involved in a 10-year longitudinal follow-up study for prognostic purposes. Structural measurements of RNFL thickness were performed using different Spectralis OCT protocols: fast macular thickness protocol to measure macular RNFL, and fast RNFL thickness protocol and fast RNFL-N thickness protocol to measure peripapillary RNFL. Binary classifiers such as multiple linear regression (MLR), support vector machines (SVM), decision tree (DT), k-nearest neighbours (k-NN), Naïve Bayes (NB), ensemble classifier (EC) and long short-term memory (LSTM) recurrent neural network were tested. For MS diagnosis, the best acquisition protocol was fast macular thickness protocol using k-NN (accuracy: 95.8%; sensitivity: 94.4%; specificity: 97.2%; precision: 97.1%; AUC: 0.958). For MS prognosis, our model with a 3-year follow up to predict disability progression 8 years later was the best predictive model. DT performed best for fast macular thickness protocol (accuracy: 91.3%; sensitivity: 90.0%; specificity: 92.5%; precision: 92.3%; AUC: 0.913) and SVM for fast RNFL-N thickness protocol (accuracy: 91.3%; sensitivity: 87.5%; specificity: 95.0%; precision: 94.6%; AUC: 0.913). This work concludes that measurements of RNFL thickness obtained with Spectralis OCT have a good ability to diagnose MS and to predict disability progression in MS patients. This machine learning approach would help clinicians to have valuable information. © 2022, The Author(s)

Computational methods for new clinical applications using imaging techniques

Esta tesis tiene por objetivo desarrollar diferentes métodos computacionales con aplicación clínica en varias enfermedades. De este modo, la investigación aquí presentada pretende aumentar el conocimiento sobre cómo el análisis y el estudio de los datos procedentes de técnicas de imagen pueden convertirse en un gran valor clínico para los profesionales de la medicina. Por lo tanto, dichos métodos pueden ser incorporados en la práctica clínica, lo que supone un beneficio para el paciente.Por un lado, la mejora de los diferentes dispositivos de imagen aumenta el abanico de posibilidades de análisis y presentación de los datos. Algunas técnicas de imagen arrojan directamente datos numéricos que tradicionalmente sólo se usaban para la monitorización de enfermedades. Sin embargo, dichos datos pueden ser empleados como biomarcadores tanto para el diagnóstico como para la predicción de enfermedades mediante la inteligencia artificial. Hoy en día, la inteligencia artificial se utiliza en muchos campos ya que todo lo que proporciona datos es abordable por estas nuevas tecnologías. Parece que no hay límite y se están desarrollando nuevas aplicaciones que hace sólo unas décadas parecían imposibles.Por otro lado, las técnicas de imagen nos permiten analizar diferentes partes del cuerpo humano en los respectivos pacientes y compararlas con controles sanos. Del mismo modo, con las imágenes se puede realizar el seguimiento de los tratamientos aplicados en dichos pacientes y, así, verificar su eficacia. Además, estas tecnologías, que proporcionan imágenes de alta resolución, son fáciles de usar, rentables y objetivas.Para resumir, esta tesis se ha centrado en desarrollar varias aplicaciones clínicas, basadas en los métodos numéricos descritos, que podrían ser una poderosa herramienta para aportar mayor información que ayude a los clínicos en la toma de decisiones.This thesis aims to develop different computational methods with clinical application in various diseases. In this way, the research presented here aims to increase knowledge on how the analysis and study of data from imaging techniques can be of great clinical value to medical professionals. Therefore, these methods can be incorporated into clinical practice, which is of benefit to the patient. On the one hand, the improvement of different imaging devices increases the range of possibilities for data analysis and presentation. Some imaging techniques directly yield numerical data that were traditionally only used for disease monitoring. However, these data can be used as biomarkers for both diagnosis and disease prediction using artificial intelligence. Today, artificial intelligence is used in many fields as everything that provides data can be addressed by these new technologies. There seems to be no limit and new applications are being developed that only a few decades ago seemed impossible. On the other hand, imaging techniques allow us to analyse different parts of the human body in the respective patients and compare them with healthy controls. In the same way, imaging can be used to monitor the treatments applied to these patients and, thus, verify their efficacy. Moreover, these technologies, which provide high-resolution images, are easy to use, cost-effective and objective. To summarise, this thesis has focused on developing several clinical applications, based on the described numerical methods, which could be a powerful tool to provide further information to help clinicians in decision making.<br /

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

Diagnosis of multiple sclerosis using optical coherence tomography supported by artificial intelligence

Background: Current procedures for diagnosing multiple sclerosis (MS) present a series of limitations, making it critically important to identify new biomarkers. The aim of the study was to identify new biomarkers for the early diagnosis of MS using spectral-domain optical coherence tomography (OCT) and artificial intelligence. Methods: Spectral domain OCT was performed on 79 patients with relapsing-remitting multiple sclerosis (RRMS) (disease duration ≤ 2 years, no history of optic neuritis) and on 69 age-matched healthy controls using the posterior pole protocol that incorporates the anatomic Positioning System. Median retinal thickness values in both eyes and inter-eye difference in healthy controls and patients were evaluated by area under the receiver operating characteristic (AUROC) curve analysis in the foveal, parafoveal and perifoveal areas and in the overall area spanned by the three rings. The structures with the greatest discriminant capacity — retinal thickness and inter-eye difference — were used as inputs to a convolutional neural network to assess the diagnostic capability. Results: Analysis of retinal thickness and inter-eye difference in RRMS patients revealed that greatest alteration occurred in the ganglion cell (GCL), inner plexiform (IPL), and inner retinal (IRL) layers. By using the average thickness of the GCL (AUROC = 0.82) and the inter-eye difference in the IPL (AUROC = 0.71) as inputs to a two-layer convolutional neural network, automatic diagnosis attained accuracy = 0.87, sensitivity = 0.82, and specificity = 0.92. Conclusion: This study adds weight to the argument that neuroretinal structure analysis could be incorporated into the diagnostic criteria for MS

Evaluación electrofisiologica y neuro-oftalmológica con tecnologia de última generación en pacientes con esclerosis múltiple

1. ObjetivoEl objetivo de esta tesis doctoral es evaluar la capacidad de discriminar entre sujetos sanos y pacientes con esclerosis múltiple (EM) mediante técnicas de aprendizaje automático utilizando datos de tomografía de coherencia óptica (OCT). Por otro lado, se ha estudiado si un método de análisis novedoso aumentaría el valor diagnóstico del electrorretinograma multifocal (mfERG) en el diagnóstico de la EM en etapa temprana.2.MetodologíaSe estudiaron diversas cohortes de sujetos sanos y pacientes con EM. Se utilizó el dispositivo Triton (Topcon, Japón) con un protocolo de OCT de campo amplio que se centra tanto en la mácula (ETDRS: exploración del estudio de retinopatía diabética de tratamiento temprano) como en el área peripapilar (TSNIT: exploración temporal-superior-nasal-inferior-temporal). Se empleó también el OCT Cirrus High Definition del que se extrajeron los valores de capa de fibras nerviosas de la retina (CNFR) del protocolo “optic disc 200x200” y los espesores de retina y capa de células ganglionares (CCG) del protocolo “macular cube 512x512”.Se registraron los valores de latencia de la onda P100 obtenida mediante potenciales evocados visuales (PEV) y la amplitud y latencia de las ondas N1 y P1 obtenidas con mfERG. Se utilizó el análisis estándar basado en latencias y amplitudes y un nuevo método para evaluar el error cuadrático medio normalizado (FNRMSE) entre las señales del modelo y los registros mfERG.Se analizó la función visual mediante la medición de la visión cromática (con test de Ishihara), de la sensibilidad al contraste (CSV-1000), de la agudeza visual (con optotipos de Snellen y ETDRS) y campo visual.3. ResultadosEn los pacientes con EM, la OCT reveló una correlación moderada entre el aumento de EDSS y el adelgazamiento de la CFNR y este a su vez se correlacionó moderadamente con una menor calidad de vida. El anillo 3 del mfERG es el que mejor discrimina entre sujetos sanos y con EM, no obstante, el nuevo análisis de señal basado en el error cuadrático medio muestra un poder de discriminación mayor que el método estándar.En análisis mediante support vector machine (SVM) sugiere que la variable más discriminante es el grosor total de GCL ++ (entre la membrana limitante interna y los límites de la capa nuclear interna), evaluada en el área peripapilar.A excepción de la GCL+ (entre CFNR y los límites de la capa nuclear interna) que muestra un adelgazamiento continuo a lo largo de la vida, el resto de las capas de la retina parece adelgazarse a partir de la 3ª década de vida.4.ConclusionesLos pacientes con esclerosis múltiple presentan una pérdida axonal progresiva de la capa de fibras nerviosas. Es posible clasificar sujetos controles sanos y pacientes con EM sin episodios previos de neuritis óptica, aplicando técnicas de aprendizaje automático para detectar la neurodegeneración subclínica estructural de la retina.<br /