L'évolution de la texture ou de la forme d'une tumeur à l'imagerie médicale reflète les modifications internes dues à la progression (naturelle ou sous traitement) d'une lésion tumorale. Dans ces travaux nous avons souhaité étudier l'apport des caractéristiques delta-radiomiques pour prédire l'évolution de la maladie. Nous cherchons à fournir un pipeline complet de la reconstruction des lésions à la prédiction, en utilisant seulement les données obtenues en routine clinique.Tout d'abord, nous avons étudié un sous ensemble de marqueurs radiomiques calculés sur IRM, en cherchant à établir quelles conditions sont nécessaires pour assurer leur robustesse. Des jeux de données artificiels et cliniques nous permettent d'évaluer l'impact de la reconstruction 3D des zones d'intérêt et celui du traitement de l'image.Une première analyse d'un cas clinique met en évidence des descripteurs de texture statistiquement associés à la survie sans évènement de patients atteints d'un carcinome du canal anal dès le diagnostic.Dans un second temps, nous avons développé des modèles d'apprentissage statistique. Une seconde étude clinique révèle qu'une signature radiomique IRM en T2 à trois paramètres apprise par un modèle de forêts aléatoires donne des résultats prometteurs pour prédire la réponse histologique des sarcomes des tissus mous à la chimiothérapie néoadjuvante.Le pipeline d'apprentissage est ensuite testé sur un jeu de données de taille moyenne sans images, dans le but cette fois de prédire la rechute métastatique à court terme de patientes atteinte d'un cancer du sein. La classification des patientes est ensuite comparée à la prédiction du temps de rechute fournie par un modèle mécanistique de l'évolution des lésions.Enfin nous discutons de l'apport des techniques plus avancées de l'apprentissage statistique pour étendre l'automatisation de notre chaîne de traitement (segmentation automatique des tumeurs, analyse quantitative de l'oedème péri-tumoral). / Tumor shape and texture evolution may highlight internal modifications resulting from the progression of cancer. In this work, we want to study the contribution of delta-radiomics features to cancer-evolution prediction. Our goal is to provide a complete pipeline from the 3D reconstruction of the volume of interest to the prediction of its evolution, using routinely acquired data only.To this end, we first analyse a subset of MRI(-extracted) radiomics biomarquers in order to determine conditions that ensure their robustness. Then, we determine the prerequisites of features reliability and explore the impact of both reconstruction and image processing (rescaling, grey-level normalization). A first clinical study emphasizes some statistically-relevant MRI radiomics features associated with event-free survival in anal carcinoma.We then develop machine-learning models to improve our results.Radiomics and machine learning approaches were then combined in a study on high grade soft tissu sarcoma (STS). Combining Radiomics and machine-learning approaches in a study on high-grade soft tissue sarcoma, we find out that a T2-MRI delta-radiomic signature with only three features is enough to construct a classifier able to predict the STS histological response to neoadjuvant chemotherapy. Our ML pipeline is then trained and tested on a middle-size clinical dataset in order to predict early metastatic relapse of patients with breast cancer. This classification model is then compared to the relapsing time predicted by the mechanistic model.Finally we discuss the contribution of deep-learning techniques to extend our pipeline with tumor automatic segmentation or edema detection.

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[ES] En los últimos años, los investigadores han intentado explotar la información de las imágenes médicas a través de la evaluación de parámetros cuantitativos para ayudar a los clínicos con el diagnóstico de enfermedades. Esta práctica ha sido bautizada como radiomics. El análisis de texturas proporciona una gran variedad de parámetros que permiten cuantificar la heterogeneidad característica de diferentes tejidos, especialmente cuando se obtienen de imagen por resonancia magnética (IRM). Basándonos en esto, decidimos estudiar las posibilidades de los parámetros texturales extraídos de IRM para caracterizar varios trastornos cerebrales. El potencial de las texturas se analizó con enfoques de aprendizaje automático, usando diferentes clasificadores y métodos de selección de características para hallar el modelo óptimo para cada tarea específica. En esta tesis, la metodología radiomics se usó para realizar cuatro proyectos independientes. En el primer proyecto, estudiamos la diferenciación entre glioblastomas multiformes (GBMs) y metástasis cerebrales (MCs) en IRM convencional. Estos tipos de tumores cerebrales pueden confundirse al diagnosticarse, ya que presentan un perfil radiológico similar y los datos clínicos pueden no ser concluyentes. Con el fin de evitar procedimientos exhaustivos e invasivos, estudiamos el poder discriminatorio de texturas 2D extraídas de imágenes de referencia T1 filtradas y sin filtrar. Los resultados sugieren que los parámetros texturales proporcionan información sobre la heterogeneidad de los GBMs y las MCs que puede servir para distinguir con precisión ambas lesiones cuando se utiliza un enfoque de aprendizaje automático adecuado. En el segundo proyecto, analizamos la clasificación de las MCs según su origen primario en IRM de referencia. En un porcentaje de pacientes, las MCs son diagnosticadas como la primera manifestación de un tumor primario desconocido. Con el fin de detectar el tumor primario de una forma no invasiva y más rápida, examinamos la capacidad del análisis de texturas 2D y 3D para diferenciar las MCs derivadas de los tumores primarios más propensos a metastatizar (cáncer de pulmón, cáncer de mama y melanoma) en imágenes T1. Los resultados mostraron que se logra una alta precisión al usar un conjunto reducido de texturas 3D para diferenciar MCs de cáncer de pulmón de MCs de cáncer de mama y melanoma. En el tercer proyecto, evaluamos las propiedades del hipocampo en IRM para identificar las diferentes etapas de la enfermedad de Alzheimer (EA). Los criterios actuales para diagnosticar la EA requieren la presencia de déficits cognitivos severos. Con la idea de establecer nuevos biomarcadores para detectar la EA en sus primeras etapas, evaluamos un conjunto de texturas 2D y 3D extraídas de IRM del hipocampo de pacientes con EA avanzada, deterioro cognitivo leve y normalidad cognitiva. Muchos parámetros de textura 3D resultaron ser estadísticamente significativos para diferenciar entre pacientes con EA y sujetos de las otras dos poblaciones. Al combinar estos parámetros con técnicas de aprendizaje automático, se obtuvo una alta precisión. En el cuarto proyecto, intentamos caracterizar los patrones de heterogeneidad del ictus cerebral isquémico en IRM estructural. En IRM cerebral de individuos de edad avanzada, algunos procesos patológicos presentan características similares, como las lesiones por ictus y las hiperintensidades de la sustancia blanca (HSBs). Dado que los ictus afectan también al tejido adyacente, decidimos estudiar la viabilidad de texturas 3D extraídas de las HSBs, la sustancia blanca no afectada y las estructuras subcorticales para diferenciar sujetos afectados por ictus lacunares o corticales visibles en IRM convencional (imágenes T1, T2 y FLAIR) de sujetos sin ictus. Las texturas no sirvieron para diferenciar ictus corticales y lacunares, pero se lograron resultados prometedores para discernir pacientes qu / [CA] En els últims anys, els investigadors han intentat explotar la informació de les imatges mèdiques a través de l'avaluació de nombrosos paràmetres quantitatius per ajudar els clínics amb el diagnòstic i la valoració de malalties. Aquesta pràctica ha sigut batejada com radiomics,. L'anàlisi de textures proporciona una gran varietat de paràmetres que permeten quantificar l'heterogeneïtat característica de diferents teixits, especialment quan s'obtenen a partir d'imatge per ressonància magnètica (IRM). Basant-nos en aquests fets, vam decidir estudiar les possibilitats dels paràmetres texturals extrets d'IRM per caracteritzar diversos trastorns cerebrals. El potencial de les textures es va analitzar amb mètodes d'aprenentatge automàtic, usant diferents classificadors i mètodes de selecció de característiques per trobar el model òptim per a cada tasca específica. En aquesta tesi, la metodologia radiomics es va emprar per realitzar quatre projectes independents. En el primer projecte, vam estudiar la diferenciació entre glioblastomes multiformes (GBMs) i metàstasis cerebrals (MCs) en IRM convencional. Aquests tipus de tumors cerebrals poden confondre's al diagnosticar-se ja que presenten un perfil radiològic similar i les dades clíniques poden no ser concloents. Per tal d'evitar procediments exhaustius i invasius, vam estudiar el poder discriminatori de textures 2D extretes d'imatges de referència T1 filtrades i sense filtrar. Els resultats suggereixen que els paràmetres texturals proporcionen informació sobre l'heterogeneïtat dels GBMs i les MCs que pot servir per distingir amb precisió ambdues lesions quan s'utilitza una aproximació d'aprenentatge automàtic adequada. En el segon projecte, vam analitzar la classificació de MCs segons el seu origen primari en IRM de referència. En un percentatge de pacients, les MCs són diagnosticades com la primera manifestació d'un tumor primari desconegut. Per tal de detectar el tumor primari d'una forma no invasiva i més ràpida, vam examinar la capacitat de l'anàlisi de textura 2D i 3D per diferenciar les MCs derivades dels tumors primaris més propensos a metastatitzar (càncer de pulmó, càncer de mama i melanoma) en imatges T1. Els resultats van mostrar que s'aconsegueix una alta precisió quan s'utilitza un conjunt reduït de textures 3D per diferenciar les MCs de càncer de pulmó de les MCs de càncer de mama i melanoma. En el tercer projecte, vam avaluar les propietats de l'hipocamp en la IRM per identificar les diferents etapes de la malaltia d'Alzheimer (MA). Els criteris actuals per diagnosticar la MA requereixen la presència de dèficits cognitius severs. Amb la idea d'establir nous biomarcadors per detectar la MA en les seues primeres etapes, vam avaluar un conjunt de textures 2D i 3D extretes d'IRM de l'hipocamp de pacients amb MA avançada, deteriorament cognitiu lleu i normalitat cognitiva. Molts paràmetres de textura 3D van resultar ser estadísticament significatius per diferenciar entre pacients amb MA i individus de les altres dues poblacions. En combinar aquests paràmetres amb tècniques d'aprenentatge automàtic, es va obtenir una alta precisió. En el quart projecte, vam intentar caracteritzar els patrons d'heterogeneïtat de l'ictus cerebral isquèmic en la IRM estructural. En la IRM cerebral d'individus d'edat avançada, alguns processos patològics presenten característiques similars, com les lesions per ictus i les hiperintensitats de la substància blanca (HSBs). Atès que els ictus tenen efecte també en teixit adjacent, vam decidir estudiar la viabilitat de textures 3D extretes de les HSBs, la substància blanca no afectada i les estructures subcorticals per diferenciar individus afectats per ictus llacunars o corticals visibles en IRM convencional (imatges T1, T2 i FLAIR) d'individus sense ictus. Les textures no foren útils per diferenciar ictus corticals i llacunars, però es van obtenir resultats prometedors per disce / [EN] Over the last years, researchers have attempted to exploit the information provided by medical images through the evaluation of numerous imaging quantitative parameters in order to help clinicians with the diagnosis and assessment of many lesions and diseases. This practice has been recently named as radiomics. Texture analysis supply a wide range of features that allow quantifying the distinctive heterogeneity of different tissues, especially when obtained from magnetic resonance imaging (MRI). With this in mind, we decided to study the possibilities of texture features from MRI in order to characterize several disorders that affect the human brain. The potential of texture features was analyzed with various machine learning approaches, involving different classifiers and feature selection methods so as to find the optimal model to accomplish each specific task. In this thesis, the radiomics methodology was used to perform four independent projects. In the first project, we studied the differentiation between glioblastomas (GBMs) and brain metastases (BMs) in conventional MRI. Sometimes these types of brain tumors can be misdiagnosed since they may present a similar radiological profile and the clinical data may be inconclusive. With the aim of avoiding exhaustive and invasive procedures, we studied the discriminatory power of a large amount of 2D texture features extracted from baseline original and filtered T1-weighted images. The results suggest that 2D texture features provide some heterogeneity information of GBMs and BMs that can help in their accurate discernment when using the proper machine learning approach. In the second project, we analyzed the classification of BMs by their primary site of origin in baseline MRI. A percentage of patients are diagnosed with BM as the first manifestation of an unknown primary tumor. In order to detect the primary tumor in a faster non-invasive way, we examined the capability of 2D and 3D texture analysis to differentiate BMs derived from the most common primary tumors (lung cancer, breast cancer and melanoma) in T1-weighted images. The results showed that high accuracy was achieved when using a reduced set of 3D descriptors to differentiate lung cancer BMs from breast cancer and melanoma BMs. In the third project, we evaluated the hippocampus MRI profile of Alzheimer's disease (AD) patients to identify the different stages of the disease. The current criteria for diagnosing AD require the presence of relevant cognitive deficits. With the purpose of establishing new biomarkers to detect AD in its early stages, we evaluated a set of 2D and 3D texture features extracted from MRI scans of the hippocampus of patients with advanced AD, early mild cognitive impairment and cognitive normality. Many 3D texture parameters resulted to be statistically significant to differentiate between AD patients and subjects from the other two populations. When combining these 3D parameters with machine learning techniques, high accuracy was obtained. In the fourth project, we attempted to characterize the heterogeneity patterns of ischemic stroke in structural MRI. In brain MRI of older individuals, some pathological processes present similar imaging characteristics, like in the case of stroke lesions and white matter hyperintensities (WMH) of diverse natures. Given that stroke effects are present not only in the affected region, but also in unaffected tissue, we investigated the feasibility of 3D texture features from WMH, normal-appearing white matter and subcortical structures to differentiate individuals who had a lacunar or cortical stroke visible on conventional brain MRI (T1-weighted, T2-weighted and FLAIR images) from subjects who did not. Texture features were not useful to differentiate between post-acute cortical and lacunar strokes, but promising results were achieved for discerning between patients presenting an old stroke and normal-ageing patients who never had a stroke. / Ortiz Ramón, R. (2019). Radiomics for diagnosis and assessing brain diseases: an approach based on texture analysis on magnetic resonance imaging [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/119118

Cancer is a leading cause of death globally, and early detection is crucial for better outcomes. This research aims to improve Region Of Interest (ROI) segmentation and feature extraction in medical image analysis using Radiomics techniques with 3D Slicer, Pyradiomics, and Python. Dimension reduction methods, including PCA, K-means, t-SNE, ISOMAP, and Hierarchical Clustering, were applied to highdimensional features to enhance interpretability and efficiency. The study assessed the ability of the reduced feature set to predict T-staging, an essential component of the TNM system for cancer diagnosis. Multinomial logistic regression models were developed and evaluated using MSE, AIC, BIC, and Deviance Test. The dataset consisted of CT and PET-CT DICOM images from 131 lung cancer patients. Results showed that PCA identified 14 features, Hierarchical Clustering 17, t-SNE 58, and ISOMAP 40, with texture-based features being the most critical. This study highlights the potential of integrating Radiomics and unsupervised learning techniques to enhance cancer prediction from medical images.

A better understanding of tumour heterogeneity is central for accurate diagnosis, targeted therapy and personalised treatment of glioblastoma patients. This thesis aims to investigate whether pre-operative multi-parametric magnetic resonance imaging (MRI) can provide a useful tool for evaluating inter-tumoural and intra-tumoural heterogeneity of glioblastoma. For this purpose, we explored: 1) the utilities of habitat imaging in combining multi-parametric MRI for identifying invasive sub-regions (I & II); 2) the significance of integrating multi-parametric MRI, and extracting modality inter-dependence for patient stratification (III & IV); 3) the value of advanced physiological MRI and radiomics approach in predicting epigenetic phenotypes (V). The following observations were made: I. Using a joint histogram analysis method, habitats with different diffusivity patterns were identified. A non-enhancing sub-region with decreased isotropic diffusion and increased anisotropic diffusion was associated with progression-free survival (PFS, hazard ratio [HR] = 1.08, P < 0.001) and overall survival (OS, HR = 1.36, P < 0.001) in multivariate models. II. Using a thresholding method, two low perfusion compartments were identified, which displayed hypoxic and pro-inflammatory microenvironment. Higher lactate in the low perfusion compartment with restricted diffusion was associated with a worse survival (PFS: HR = 2.995, P = 0.047; OS: HR = 4.974, P = 0.005). III. Using an unsupervised multi-view feature selection and late integration method, two patient subgroups were identified, which demonstrated distinct OS (P = 0.007) and PFS (P < 0.001). Features selected by this approach showed significantly incremental prognostic value for 12-month OS (P = 0.049) and PFS (P = 0.022) than clinical factors. IV. Using a method of unsupervised clustering via copula transform and discrete feature extraction, three patient subgroups were identified. The subtype demonstrating high inter-dependency of diffusion and perfusion displayed higher lactate than the other two subtypes (P = 0.016 and P = 0.044, respectively). Both subtypes of low and high inter-dependency showed worse PFS compared to the intermediate subtype (P = 0.046 and P = 0.009, respectively). V. Using a radiomics approach, advanced physiological images showed better performance than structural images for predicting O6-methylguanine-DNA methyltransferase (MGMT) methylation status. For predicting 12-month PFS, the model of radiomic features and clinical factors outperformed the model of MGMT methylation and clinical factors (P = 0.010). In summary, pre-operative multi-parametric MRI shows potential for the non-invasive evaluation of glioblastoma heterogeneity, which could provide crucial information for patient care.

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Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.