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Purpose: High-grade glioma (HGG) is a common form of malignant primary brain cancer with poor prognosis. The diffusive nature of HGGs implies that tumor cell invasion of normal tissue extends several centimeters away from the visible gross tumor volume (GTV). The standard methodology for clinical volume target (CTV) delineation is to apply a 2- to 3-cm margin around the GTV. However, tumor recurrence is extremely frequent. The purpose of this paper was to introduce a framework and computational model for the prediction of normal tissue HGG cell invasion and to investigate the agreement of the conventional CTV delineation with respect to the predicted tumor invasion. Methods and Materials: A model for HGG cell diffusion and proliferation was implemented and used to assess the tumor invasion patterns for 112 cases of HGGs. Normal brain structures and tissues as well as the GTVs visible on diagnostic images were delineated using automated methods. The volumes encompassed by different tumor cell concentration isolines calculated using the model for invasion were compared with the conventionally delineated CTVs, and the differences were analyzed. The 3-dimensional-Hausdorff distance between the CTV and the volumes encompassed by various isolines was also calculated. Results: In 50% of cases, the CTV failed to encompass regions containing tumor cell concentrations of 614 cells/mm³ or greater. In 84% of cases, the lowest cell concentration completely encompassed by the CTV was ≥1 cell/mm³. In the remaining 16%, the CTV overextended into normal tissue. The Hausdorff distance was on average comparable to the CTV margin. Conclusions: The standard methodology for CTV delineation appears to be inconsistent with HGG invasion patterns in terms of size and shape. Tumor invasion modeling could therefore be useful in assisting in the CTV delineation for HGGs.

Cancer is a major public health problem, accounting for an estimated 10 million deaths worldwide in 2020 alone. Rapid advances in the field of image acquisition and hardware development over the past three decades have resulted in the development of modern medical imaging modalities that can capture high-resolution anatomical, physiological, functional, and metabolic quantitative information from cancerous organs. Therefore, the applications of medical imaging have become increasingly crucial in the clinical routines of oncology, providing screening, diagnosis, treatment monitoring, and non/minimally-invasive evaluation of disease prognosis. The essential need for medical images, however, has resulted in the acquisition of a tremendous number of imaging scans. Considering the growing role of medical imaging data on one side and the challenges of manually examining such an abundance of data on the other side, the development of computerized tools to automatically or semi-automatically examine the image data has attracted considerable interest. Hence, a variety of machine learning tools have been developed for oncological image analysis, aiming to assist clinicians with repetitive tasks in their workflow. This thesis aims to contribute to the field of oncological image analysis by proposing new ways of quantifying tumor characteristics from medical image data. Specifically, this thesis consists of six studies, the first two of which focus on introducing novel methods for tumor segmentation. The last four studies aim to develop quantitative imaging biomarkers for cancer diagnosis and prognosis. The main objective of Study I is to develop a deep learning pipeline capable of capturing the appearance of lung pathologies, including lung tumors, and integrating this pipeline into the segmentation networks to leverage the segmentation accuracy. The proposed pipeline was tested on several comprehensive datasets, and the numerical quantifications show the superiority of the pr, Cancer är en global hälsoutmaning som uppskattas ansvara för cirka 10 miljoner dödsfall i hela världen, bara under året 2020. Framsteg inom medicinsk bildtagning och hårdvaruutveckling de senaste tre decennierna har banat vägen för moderna medicinska bildgivande system vars upplösningsförmåga tillåter att fånga information om tumörers anatomi, fysiologi, funktion samt metabolism. Medicinsk bildanalys har därför fått en mer betydelserik roll i klinikers dagliga rutiner inom onkologin, för bland annat screening, diagnostik, uppföljning av behandling samt icke-invasiv utvärdering av sjukdomsprognoser. Sjukvårdens behov av medicinska bilder har lett till att det nu på sjukhusen finns en enorm mängd medicinska bilder på alla moderna sjukhus. Med hänsyn till den viktiga roll medicinsk bilddata spelar i dagens sjukvård, samt den mängd manuellt arbete som behöver göras för att analysera den mängd data som genereras varje dag, så har utvecklingen av digitala verktyg för att för att automatiskt eller semi-automatiskt analysera bilddatan alltid haft stort intresse. Därför har en rad maskininlärningsverktyg utvecklats för analys av onkologisk data, för att gripa sig an läkares repetitiva vardagssysslor. Den här avhandlingen syftar att bidra till fältet “onkologisk bildanalys” genom att föreslå nya sätt att kvantifiera tumörers egenskaper från medicinsk bilddata. Specifikt, är denna avhandling baserad på sex artiklar där de första två har fokus att presentera nya metoder för segmentering av tumörer, och de resterande fyra ämnar att utveckla kvantitativa biomarkörer för cancerdiagnostik och prognos. Huvudsyftet för “Studie I” har varit att utveckla en djupinlärnings-pipeline vars syfte är att fånga lungpatalogiers anatomier (inklusive lungtumörer) samt integrera detta med djupa neurala nätverk för segmentering för att nyttja det första nätverkets utfall för att förbättra segmenteringskvalitén. Den föreslagna pipelinen testades på flertalet dataset och numeriska analyser visar en, QC 2022-08-29

Segmentation of lung pathology in Computed Tomography (CT) images is of great importance for lung disease screening. However, the presence of different types of lung pathologies with a wide range of heterogeneities in size, shape, location, and texture, on one side, and their visual similarity with respect to surrounding tissues, on the other side, make it challenging to perform reliable automatic lesion seg-mentation. To leverage segmentation performance, we propose a deep learning framework comprising a Normal Appearance Autoencoder (NAA) model to learn the distribution of healthy lung regions and re-construct pathology-free images from the corresponding pathological inputs by replacing the pathological regions with the characteristics of healthy tissues. Detected regions that represent prior information re-garding the shape and location of pathologies are then integrated into a segmentation network to guide the attention of the model into more meaningful delineations. The proposed pipeline was tested on three types of lung pathologies, including pulmonary nodules, Non-Small Cell Lung Cancer (NSCLC), and Covid-19 lesion on five comprehensive datasets. The results show the superiority of the proposed prior model, which outperformed the baseline segmentation models in all the cases with significant margins. On av-erage, adding the prior model improved the Dice coefficient for the segmentation of lung nodules by 0.038, NSCLCs by 0.101, and Covid-19 lesions by 0.041. We conclude that the proposed NAA model pro-duces reliable prior knowledge regarding the lung pathologies, and integrating such knowledge into a prior segmentation network leads to more accurate delineations., QC 20220627

ObjectiveSurvival Rate Prediction (SRP) is a valuable tool to assist in the clinical diagnosis and treatment planning of lung cancer patients. In recent years, deep learning (DL) based methods have shown great potential in medical image processing in general and SRP in particular. This study proposes a fully-automated method for SRP from computed tomography (CT) images, which combines an automatic segmentation of the tumor and a DL-based method for extracting rotational-invariant features. MethodsIn the first stage, the tumor is segmented from the CT image of the lungs. Here, we use a deep-learning-based method that entails a variational autoencoder to provide more information to a U-Net segmentation model. Next, the 3D volumetric image of the tumor is projected onto 2D spherical maps. These spherical maps serve as inputs for a spherical convolutional neural network that approximates the log risk for a generalized Cox proportional hazard model. ResultsThe proposed method is compared with 17 baseline methods that combine different feature sets and prediction models using three publicly-available datasets: Lung1 (n=422), Lung3 (n=89), and H&N1 (n=136). We observed comparable C-index scores compared to the best-performing baseline methods in a 5-fold cross-validation on Lung1 (0.59 +/- 0.03 vs. 0.62 +/- 0.04). In comparison, it slightly outperforms all methods in inter-data set evaluation (0.64 vs. 0.63). The best-performing method from the first experiment reduced its performance to 0.61 and 0.62 for Lung3 and H&N1, respectively. DiscussionThe experiments suggest that the performance of spherical features is comparable with previous approaches, but they generalize better when applied to unseen datasets. That might imply that orientation-independent shape features are relevant for SRP. The performance of the proposed method was very similar, using manual and automatic segmentation methods. This makes the proposed model useful in cases where expert annotations a, QC 20220601

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ObjectivesBoth radiomics and deep learning methods have shown great promise in predicting lesion malignancy in various image-based oncology studies. However, it is still unclear which method to choose for a specific clinical problem given the access to the same amount of training data. In this study, we try to compare the performance of a series of carefully selected conventional radiomics methods, end-to-end deep learning models, and deep-feature based radiomics pipelines for pulmonary nodule malignancy prediction on an open database that consists of 1297 manually delineated lung nodules. MethodsConventional radiomics analysis was conducted by extracting standard handcrafted features from target nodule images. Several end-to-end deep classifier networks, including VGG, ResNet, DenseNet, and EfficientNet were employed to identify lung nodule malignancy as well. In addition to the baseline implementations, we also investigated the importance of feature selection and class balancing, as well as separating the features learned in the nodule target region and the background/context region. By pooling the radiomics and deep features together in a hybrid feature set, we investigated the compatibility of these two sets with respect to malignancy prediction. ResultsThe best baseline conventional radiomics model, deep learning model, and deep-feature based radiomics model achieved AUROC values (mean +/- standard deviations) of 0.792 +/- 0.025, 0.801 +/- 0.018, and 0.817 +/- 0.032, respectively through 5-fold cross-validation analyses. However, after trying out several optimization techniques, such as feature selection and data balancing, as well as adding context features, the corresponding best radiomics, end-to-end deep learning, and deep-feature based models achieved AUROC values of 0.921 +/- 0.010, 0.824 +/- 0.021, and 0.936 +/- 0.011, respectively. We achieved the best prediction accuracy from the hybrid feature set (AUROC: 0.938 +/- 0.010). ConclusionThe end-to-end dee, QC 20220124

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We propose a hybrid segmentation pipeline based on the autoencoders’ capability of anomaly detection. To this end, we, first, introduce a new augmentation technique to generate synthetic paired images. Gaining advantage from the paired images, we propose a Normal Appearance Autoencoder (NAA) that is able to remove tumors and thus reconstruct realistic-looking, tumor-free images. After estimating the regions where the abnormalities potentially exist, a segmentation network is guided toward the candidate region. We tested the proposed pipeline on the BraTS 2019 database. The preliminary results indicate that the proposed model improved the segmentation accuracy of brain tumor subregions compared to the U-Net model., QC 20210622

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