Javier Ramı́rez

Francisco J. Martinez-Murcia, Juan M. Górriz, Javier Ramírez et al.

Spatial and intensity normalization are nowadays a prerequisite for neuroimaging analysis. Influenced by voxel-wise and other univariate comparisons, where these corrections are key, they are commonly applied to any type of analysis and imaging modalities. Nuclear imaging modalities such as PET-FDG or FP-CIT SPECT, a common modality used in Parkinson's Disease diagnosis, are especially dependent on intensity normalization. However, these steps are computationally expensive and furthermore, they may introduce deformations in the images, altering the information contained in them. Convolutional Neural Networks (CNNs), for their part, introduce position invariance to pattern recognition, and have been proven to classify objects regardless of their orientation, size, angle, etc. Therefore, a question arises: how well can CNNs account for spatial and intensity differences when analysing nuclear brain imaging? Are spatial and intensity normalization still needed? To answer this question, we have trained four different CNN models based on well-established architectures, using or not different spatial and intensity normalization preprocessing. The results show that a sufficiently complex model such as our three-dimensional version of the ALEXNET can effectively account for spatial differences, achieving a diagnosis accuracy of 94.1% with an area under the ROC curve of 0.984. The visualization of the differences via saliency maps shows that these models are correctly finding patterns that match those found in the literature, without the need of applying any complex spatial normalization procedure. However, the intensity normalization -- and its type -- is revealed as very influential in the results and accuracy of the trained model, and therefore must be well accounted.

Juan M Gorriz, J. Ramirez, F. Segovia et al.

Regression analysis is a central topic in statistical modeling, aimed at estimating the relationships between a dependent variable, commonly referred to as the response variable, and one or more independent variables, i.e., explanatory variables. Linear regression is by far the most popular method for performing this task in various fields of research, such as data integration and predictive modeling when combining information from multiple sources. Classical methods for solving linear regression problems, such as Ordinary Least Squares (OLS), Ridge, or Lasso regressions, often form the foundation for more advanced machine learning (ML) techniques, which have been successfully applied, though without a formal definition of statistical significance. At most, permutation or analyses based on empirical measures (e.g., residuals or accuracy) have been conducted, leveraging the greater sensitivity of ML estimations for detection. In this paper, we introduce Statistical Agnostic Regression (SAR) for evaluating the statistical significance of ML-based linear regression models. This is achieved by analyzing concentration inequalities of the actual risk (expected loss) and considering the worst-case scenario. To this end, we define a threshold that ensures there is sufficient evidence, with a probability of at least $1-η$, to conclude the existence of a linear relationship in the population between the explanatory (feature) and the response (label) variables. Simulations demonstrate the ability of the proposed agnostic (non-parametric) test to provide an analysis of variance similar to the classical multivariate $F$-test for the slope parameter, without relying on the underlying assumptions of classical methods. Moreover, the residuals computed from this method represent a trade-off between those obtained from ML approaches and the classical OLS.

Carmen Jimenez-Mesa, Yizhou Wan, Guilio Sansone et al.

Brain tumor resection is a highly complex procedure with profound implications for survival and quality of life. Predicting patient outcomes is crucial to guide clinicians in balancing oncological control with preservation of neurological function. However, building reliable prediction models is severely limited by the rarity of curated datasets that include both pre- and post-surgery imaging, given the clinical, logistical and ethical challenges of collecting such data. In this study, we develop a novel framework that integrates explainable artificial intelligence (XAI) with neuroimaging-based feature engineering for survival assessment in brain tumor patients. We curated structural MRI data from 49 patients scanned pre- and post-surgery, providing a rare resource for identifying survival-related biomarkers. A key methodological contribution is the development of a global explanation optimizer, which refines survival-related feature attribution in deep learning models, thereby improving both the interpretability and reliability of predictions. From a clinical perspective, our findings provide important evidence that survival after oncological surgery is influenced by alterations in regions related to cognitive and sensory functions. These results highlight the importance of preserving areas involved in decision-making and emotional regulation to improve long-term outcomes. From a technical perspective, the proposed optimizer advances beyond state-of-the-art XAI methods by enhancing both the fidelity and comprehensibility of model explanations, thus reinforcing trust in the recognition patterns driving survival prediction. This work demonstrates the utility of XAI-driven neuroimaging analysis in identifying survival-related variability and underscores its potential to inform precision medicine strategies in brain tumor treatment.

JM Gorriz, R. Martin-Clemente, C. G. Puntonet et al.

There remains an open question about the usefulness and the interpretation of Machine learning (MLE) approaches for discrimination of spatial patterns of brain images between samples or activation states. In the last few decades, these approaches have limited their operation to feature extraction and linear classification tasks for between-group inference. In this context, statistical inference is assessed by randomly permuting image labels or by the use of random effect models that consider between-subject variability. These multivariate MLE-based statistical pipelines, whilst potentially more effective for detecting activations than hypotheses-driven methods, have lost their mathematical elegance, ease of interpretation, and spatial localization of the ubiquitous General linear Model (GLM). Recently, the estimation of the conventional GLM has been demonstrated to be connected to an univariate classification task when the design matrix is expressed as a binary indicator matrix. In this paper we explore the complete connection between the univariate GLM and MLE \emph{regressions}. To this purpose we derive a refined statistical test with the GLM based on the parameters obtained by a linear Support Vector Regression (SVR) in the \emph{inverse} problem (SVR-iGLM). Subsequently, random field theory (RFT) is employed for assessing statistical significance following a conventional GLM benchmark. Experimental results demonstrate how parameter estimations derived from each model (mainly GLM and SVR) result in different experimental design estimates that are significantly related to the predefined functional task. Moreover, using real data from a multisite initiative the proposed MLE-based inference demonstrates statistical power and the control of false positives, outperforming the regular GLM.

Juan E. Arco, Andrés Ortiz, Javier Ramírez et al.

The ongoing crisis of the COVID-19 (Coronavirus disease 2019) pandemic has changed the world. According to the World Health Organization (WHO), 4 million people have died due to this disease, whereas there have been more than 180 million confirmed cases of COVID-19. The collapse of the health system in many countries has demonstrated the need of developing tools to automatize the diagnosis of the disease from medical imaging. Previous studies have used deep learning for this purpose. However, the performance of this alternative highly depends on the size of the dataset employed for training the algorithm. In this work, we propose a classification framework based on sparse coding in order to identify the pneumonia patterns associated with different pathologies. Specifically, each chest X-ray (CXR) image is partitioned into different tiles. The most relevant features extracted from PCA are then used to build the dictionary within the sparse coding procedure. Once images are transformed and reconstructed from the elements of the dictionary, classification is performed from the reconstruction errors of individual patches associated with each image. Performance is evaluated in a real scenario where simultaneously differentiation between four different pathologies: control vs bacterial pneumonia vs viral pneumonia vs COVID-19. The accuracy when identifying the presence of pneumonia is 93.85%, whereas 88.11% is obtained in the 4-class classification context. The excellent results and the pioneering use of sparse coding in this scenario evidence the applicability of this approach as an aid for clinicians in a real-world environment.

Afshin Shoeibi, Parisa Moridian, Marjane Khodatars et al.

Epilepsy is a disorder of the brain denoted by frequent seizures. The symptoms of seizure include confusion, abnormal staring, and rapid, sudden, and uncontrollable hand movements. Epileptic seizure detection methods involve neurological exams, blood tests, neuropsychological tests, and neuroimaging modalities. Among these, neuroimaging modalities have received considerable attention from specialist physicians. One method to facilitate the accurate and fast diagnosis of epileptic seizures is to employ computer-aided diagnosis systems (CADS) based on deep learning (DL) and neuroimaging modalities. This paper has studied a comprehensive overview of DL methods employed for epileptic seizures detection and prediction using neuroimaging modalities. First, DL-based CADS for epileptic seizures detection and prediction using neuroimaging modalities are discussed. Also, descriptions of various datasets, preprocessing algorithms, and DL models which have been used for epileptic seizures detection and prediction have been included. Then, research on rehabilitation tools has been presented, which contains brain-computer interface (BCI), cloud computing, internet of things (IoT), hardware implementation of DL techniques on field-programmable gate array (FPGA), etc. In the discussion section, a comparison has been carried out between research on epileptic seizure detection and prediction. The challenges in epileptic seizures detection and prediction using neuroimaging modalities and DL models have been described. In addition, possible directions for future works in this field, specifically for solving challenges in datasets, DL, rehabilitation, and hardware models, have been proposed. The final section is dedicated to the conclusion which summarizes the significant findings of the paper.

Carmen Jiménez-Mesa, Javier Ramírez, John Suckling et al.

Discriminative analysis in neuroimaging by means of deep/machine learning techniques is usually tested with validation techniques, whereas the associated statistical significance remains largely under-developed due to their computational complexity. In this work, a non-parametric framework is proposed that estimates the statistical significance of classifications using deep learning architectures. In particular, a combination of autoencoders (AE) and support vector machines (SVM) is applied to: (i) a one-condition, within-group designs often of normal controls (NC) and; (ii) a two-condition, between-group designs which contrast, for example, Alzheimer's disease (AD) patients with NC (the extension to multi-class analyses is also included). A random-effects inference based on a label permutation test is proposed in both studies using cross-validation (CV) and resubstitution with upper bound correction (RUB) as validation methods. This allows both false positives and classifier overfitting to be detected as well as estimating the statistical power of the test. Several experiments were carried out using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, the Dominantly Inherited Alzheimer Network (DIAN) dataset, and a MCI prediction dataset. We found in the permutation test that CV and RUB methods offer a false positive rate close to the significance level and an acceptable statistical power (although lower using cross-validation). A large separation between training and test accuracies using CV was observed, especially in one-condition designs. This implies a low generalization ability as the model fitted in training is not informative with respect to the test set. We propose as solution by applying RUB, whereby similar results are obtained to those of the CV test set, but considering the whole set and with a lower computational cost per iteration.

Juan E. Arco, Andrés Ortiz, Javier Ramírez et al.

The outbreak of the COVID-19 (Coronavirus disease 2019) pandemic has changed the world. According to the World Health Organization (WHO), there have been more than 100 million confirmed cases of COVID-19, including more than 2.4 million deaths. It is extremely important the early detection of the disease, and the use of medical imaging such as chest X-ray (CXR) and chest Computed Tomography (CCT) have proved to be an excellent solution. However, this process requires clinicians to do it within a manual and time-consuming task, which is not ideal when trying to speed up the diagnosis. In this work, we propose an ensemble classifier based on probabilistic Support Vector Machine (SVM) in order to identify pneumonia patterns while providing information about the reliability of the classification. Specifically, each CCT scan is divided into cubic patches and features contained in each one of them are extracted by applying kernel PCA. The use of base classifiers within an ensemble allows our system to identify the pneumonia patterns regardless of their size or location. Decisions of each individual patch are then combined into a global one according to the reliability of each individual classification: the lower the uncertainty, the higher the contribution. Performance is evaluated in a real scenario, yielding an accuracy of 97.86%. The large performance obtained and the simplicity of the system (use of deep learning in CCT images would result in a huge computational cost) evidence the applicability of our proposal in a real-world environment.

Juan E. Arco, A. Ortiz, J. Ramirez et al.

Respiratory diseases kill million of people each year. Diagnosis of these pathologies is a manual, time-consuming process that has inter and intra-observer variability, delaying diagnosis and treatment. The recent COVID-19 pandemic has demonstrated the need of developing systems to automatize the diagnosis of pneumonia, whilst Convolutional Neural Network (CNNs) have proved to be an excellent option for the automatic classification of medical images. However, given the need of providing a confidence classification in this context it is crucial to quantify the reliability of the model's predictions. In this work, we propose a multi-level ensemble classification system based on a Bayesian Deep Learning approach in order to maximize performance while quantifying the uncertainty of each classification decision. This tool combines the information extracted from different architectures by weighting their results according to the uncertainty of their predictions. Performance of the Bayesian network is evaluated in a real scenario where simultaneously differentiating between four different pathologies: control vs bacterial pneumonia vs viral pneumonia vs COVID-19 pneumonia. A three-level decision tree is employed to divide the 4-class classification into three binary classifications, yielding an accuracy of 98.06% and overcoming the results obtained by recent literature. The reduced preprocessing needed for obtaining this high performance, in addition to the information provided about the reliability of the predictions evidence the applicability of the system to be used as an aid for clinicians.

Ignacio Alvarez Illan, Javier Ramirez, Juan M. Gorriz et al.

Non-mass enhancing lesions (NME) constitute a diagnostic challenge in dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of the breast. Computer Aided Diagnosis (CAD) systems provide physicians with advanced tools for analysis, assessment and evaluation that have a significant impact on the diagnostic performance. Here, we propose a new approach to address the challenge of NME detection and segmentation, taking advantage of independent component analysis (ICA) to extract data-driven dynamic lesion characterizations. A set of independent sources was obtained from DCE-MRI dataset of breast patients, and the dynamic behavior of the different tissues was described by multiple dynamic curves, together with a set of eigenimages describing the scores for each voxel. A new test image is projected onto the independent source space using the unmixing matrix, and each voxel is classified by a support vector machine (SVM) that has already been trained with manually delineated data. A solution to the high false positive rate problem is proposed by controlling the SVM hyperplane location, outperforming previously published approaches.

Juan-Manuel Torres-Moreno, Javier Ramirez, Iria da Cunha

In this paper we present REG, a graph-based approach for study a fundamental problem of Natural Language Processing (NLP): the automatic text summarization. The algorithm maps a document as a graph, then it computes the weight of their sentences. We have applied this approach to summarize documents in three languages.