| 1. |
- Astaraki, Mehdi, PhD Student, 1984-
(författare)
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Advanced Machine Learning Methods for Oncological Image Analysis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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 proposed prior-aware DL framework compared to the state of the art. Study II aims to address a crucial challenge faced by supervised segmentation models: dependency on the large-scale labeled dataset. In this study, an unsupervised segmentation approach is proposed based on the concept of image inpainting to segment lung and head-neck tumors in images from single and multiple modalities. The proposed autoinpainting pipeline shows great potential in synthesizing high-quality tumor-free images and outperforms a family of well-established unsupervised models in terms of segmentation accuracy.Studies III and IV aim to automatically discriminate the benign from the malignant pulmonary nodules by analyzing the low-dose computed tomography (LDCT) scans. In Study III, a dual-pathway deep classification framework is proposed to simultaneously take into account the local intra-nodule heterogeneities and the global contextual information. Study IV seeks to compare the discriminative power of a series of carefully selected conventional radiomics methods, end-to-end Deep Learning (DL) models, and deep features-based radiomics analysis on the same dataset. The numerical analyses show the potential of fusing the learned deep features into radiomic features for boosting the classification power.Study V focuses on the early assessment of lung tumor response to the applied treatments by proposing a novel feature set that can be interpreted physiologically. This feature set was employed to quantify the changes in the tumor characteristics from longitudinal PET-CT scans in order to predict the overall survival status of the patients two years after the last session of treatments. The discriminative power of the introduced imaging biomarkers was compared against the conventional radiomics, and the quantitative evaluations verified the superiority of the proposed feature set. Whereas Study V focuses on a binary survival prediction task, Study VI addresses the prediction of survival rate in patients diagnosed with lung and head-neck cancer by investigating the potential of spherical convolutional neural networks and comparing their performance against other types of features, including radiomics. While comparable results were achieved in intra-dataset analyses, the proposed spherical-based features show more predictive power in inter-dataset analyses.In summary, the six studies incorporate different imaging modalities and a wide range of image processing and machine-learning techniques in the methods developed for the quantitative assessment of tumor characteristics and contribute to the essential procedures of cancer diagnosis and prognosis.
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| 2. |
- Brusini, Irene
(författare)
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Methods for the analysis and characterization of brain morphology from MRI images
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brain magnetic resonance imaging (MRI) is an imaging modality that produces detailed images of the brain without using any ionizing radiation. From a structural MRI scan, it is possible to extract morphological properties of different brain regions, such as their volume and shape. These measures can both allow a better understanding of how the brain changes due to multiple factors (e.g., environmental and pathological) and contribute to the identification of new imaging biomarkers of neurological and psychiatric diseases. The overall goal of the present thesis is to advance the knowledge on how brain MRI image processing can be effectively used to analyze and characterize brain structure.The first two works presented in this thesis are animal studies that primarily aim to use MRI data for analyzing differences between groups of interest. In Paper I, MRI scans from wild and domestic rabbits were processed to identify structural brain differences between these two groups. Domestication was found to significantly reshape brain structure in terms of both regional gray matter volume and white matter integrity. In Paper II, rat brain MRI scans were used to train a brain age prediction model. This model was then tested on both controls and a group of rats that underwent long-term environmental enrichment and dietary restriction. This healthy lifestyle intervention was shown to significantly affect the predicted brain age trajectories by slowing the rats' aging process compared to controls. Furthermore, brain age predicted on young adult rats was found to have a significant effect on survival.Papers III to V are human studies that propose deep learning-based methods for segmenting brain structures that can be severely affected by neurodegeneration. In particular, Papers III and IV focus on U-Net-based 2D segmentation of the corpus callosum (CC) in multiple sclerosis (MS) patients. In both studies, good segmentation accuracy was obtained and a significant correlation was found between CC area and the patient's level of cognitive and physical disability. Additionally, in Paper IV, shape analysis of the segmented CC revealed a significant association between disability and both CC thickness and bending angle. Conversely, in Paper V, a novel method for automatic segmentation of the hippocampus is proposed, which consists of embedding a statistical shape prior as context information into a U-Net-based framework. The inclusion of shape information was shown to significantly improve segmentation accuracy when testing the method on a new unseen cohort (i.e., different from the one used for training). Furthermore, good performance was observed across three different diagnostic groups (healthy controls, subjects with mild cognitive impairment and Alzheimer's patients) that were characterized by different levels of hippocampal atrophy.In summary, the studies presented in this thesis support the great value of MRI image analysis for the advancement of neuroscientific knowledge, and their contribution is mostly two-fold. First, by applying well-established processing methods on datasets that had not yet been explored in the literature, it was possible to characterize specific brain changes and disentangle relevant problems of a clinical or biological nature. Second, a technical contribution is provided by modifying and extending already-existing brain image processing methods to achieve good performance on new datasets.
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| 3. |
- Jörgens, Daniel, 1988-
(författare)
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Development and application of rule- and learning-based approaches within the scope of neuroimaging : Tensor voting, tractography and machine learning
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The opportunity to non-invasively probe the structure and function of different parts of the human body makes medical imaging an indispensable tool in clinical diagnostics and related fields of research. Especially neuroscientists rely on modalities like structural or functional Magnetic Resonance Imaging, Computed Tomography or Positron Emission Tomography to study the human brain in vivo. But also in clinical routine, diagnosis, screening or follow-up of different pathological conditions build upon the use of neuroimaging.Computational solutions are essential for the analysis of medical images. While in the case of conventional photography the recorded signal comprises the actual image, most medical imaging devices require the reconstruction of an image from the acquired data. However, not only the image formation, but also further processing tasks to assist doctors or researchers in the interpretation of the data and eventually in subsequent decision making, rely more and more on automation. Typical tasks range from locating and measuring objects in a single patient, e.g. a particular organ, a tumour or a specific region in the brain, to comparing such measurements over time between groups consisting of large numbers of subjects. Automated solutions for these scenarios are required to model complex relations of data in the presence of acquisition noise and subject variability while assuring a tractable computational demand.Traditionally, the development of computational algorithms for medical imaging problems focused on rule-based strategies. Explicitly defined rules that encode the knowledge of the developer are characteristic for such approaches. Within the last decade, this paradigm began to change and learning-based models dramatically gained in popularity. These rely on fitting a complex model to large amounts of data samples, often annotated, which are representative for a particular problem. Instead of manually designing the sought-after solution, it is ‘learned from the data’. While these models have shown enormous potential, they also pose important questions for method developers. How can I get hold of enough data? How much data is enough? How can I obtain proper annotations?This thesis comprises six studies covering the development and the application of methods along the whole pipeline of medical image analysis. Studies I and II propose different extensions to the method of tensor voting to make it applicable in specific medical imaging problems. Studies III–V address the use of modern machine learning techniques, in particular neural networks, in the field of tractography. Notably, the challenge of obtaining adequately annotated data samples is a topic in Study V. In Study VI, a prospective neuroimaging study of unilateral ear canal atresia in adults is presented, covering the application of methods from data acquisition to group comparison. Overall, the compiled works contributed, in one way or the other, to the non-invasive extraction of knowledge from the human body through automated processing of medical images.
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| 4. |
- Astaraki, Mehdi, PhD Student, 1984-, et al.
(författare)
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A Comparative Study of Radiomics and Deep-Learning Based Methods for Pulmonary Nodule Malignancy Prediction in Low Dose CT Images
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Both 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.Methods: Conventional 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.Results: The 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).Conclusion: The end-to-end deep-learning model outperforms conventional radiomics out of the box without much fine-tuning. On the other hand, fine-tuning the models lead to significant improvements in the prediction performance where the conventional and deep-feature based radiomics models achieved comparable results. The hybrid radiomics method seems to be the most promising model for lung nodule malignancy prediction in this comparative study.
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| 5. |
- Astaraki, Mehdi, PhD Student, 1984-, et al.
(författare)
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Benign-malignant pulmonary nodule classification in low-dose CT with convolutional features
- 2021
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 83, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Low-Dose Computed Tomography (LDCT) is the most common imaging modality for lung cancer diagnosis. The presence of nodules in the scans does not necessarily portend lung cancer, as there is an intricate relationship between nodule characteristics and lung cancer. Therefore, benign-malignant pulmonary nodule classification at early detection is a crucial step to improve diagnosis and prolong patient survival. The aim of this study is to propose a method for predicting nodule malignancy based on deep abstract features.Methods: To efficiently capture both intra-nodule heterogeneities and contextual information of the pulmonary nodules, a dual pathway model was developed to integrate the intra-nodule characteristics with contextual attributes. The proposed approach was implemented with both supervised and unsupervised learning schemes. A random forest model was added as a second component on top of the networks to generate the classification results. The discrimination power of the model was evaluated by calculating the Area Under the Receiver Operating Characteristic Curve (AUROC) metric. Results: Experiments on 1297 manually segmented nodules show that the integration of context and target supervised deep features have a great potential for accurate prediction, resulting in a discrimination power of 0.936 in terms of AUROC, which outperformed the classification performance of the Kaggle 2017 challenge winner.Conclusion: Empirical results demonstrate that integrating nodule target and context images into a unified network improves the discrimination power, outperforming the conventional single pathway convolutional neural networks.
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| 6. |
- Astaraki, Mehdi, PhD Student, 1984-, et al.
(författare)
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Prior-aware autoencoders for lung pathology segmentation
- 2022
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 80, s. 102491-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
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| 8. |
- Blystad, Ida, 1972-, et al.
(författare)
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Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R-1), transverse relaxation (R-2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R-1-difference-map. The quantitative R-1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.
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| 9. |
- Brusini, Irene, et al.
(författare)
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MRI-derived brain age as a biomarker of ageing in rats : validation using a healthy lifestyle intervention
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 109, s. 204-215
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Tidskriftsartikel (refereegranskat)abstract
- The difference between brain age predicted from MRI and chronological age (the so-called BrainAGE) has been proposed as an ageing biomarker. We analyse its cross-species potential by testing it on rats undergoing an ageing modulation intervention. Our rat brain age prediction model combined Gaussian process regression with a classifier and achieved a mean absolute error (MAE) of 4.87 weeks using cross-validation on a longitudinal dataset of 31 normal ageing rats. It was then tested on two groups of 24 rats (MAE = 9.89 weeks, correlation coefficient = 0.86): controls vs. a group under long-term environmental enrichment and dietary restriction (EEDR). Using a linear mixed-effects model, BrainAGE was found to increase more slowly with chronological age in EEDR rats ( p = 0 . 015 for the interaction term). Cox re-gression showed that older BrainAGE at 5 months was associated with higher mortality risk ( p = 0 . 03 ). Our findings suggest that lifestyle-related prevention approaches may help to slow down brain ageing in rodents and the potential of BrainAGE as a predictor of age-related health outcomes.
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| 10. |
- Dohlmar, Frida, et al.
(författare)
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Validation of automated post-adjustments of HDR prostate brachytherapy treatment plans by quantitative measures and oncologist observer study
- 2023
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Ingår i: Brachytherapy. - : Elsevier BV. - 1538-4721 .- 1873-1449. ; 22:3, s. 407-415
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim was to evaluate a postprocessing optimization algorithm's ability to improve the spatial properties of a clinical treatment plan while preserving the target coverage and the dose to the organs at risk. The goal was to obtain a more homogenous treatment plan, minimizing the need for manual adjustments after inverse treatment planning. MATERIALS AND METHODS: The study included 25 previously treated prostate cancer pa-tients. The treatment plans were evaluated on dose-volume histogram parameters established clin-ical and quantitative measures of the high dose volumes. The volumes of the four largest hot spots were compared and complemented with a human observer study with visual grading by eight oncologists. Statistical analysis was done using ordinal logistic regression. Weighted kappa and Fleiss' kappa were used to evaluate intra-and interobserver reliability. RESULTS: The quantitative analysis showed that there was no change in planning target volume (PTV) coverage and dose to the rectum. There were significant improvements for the adjusted treatment plan in: V150% and V200% for PTV, dose to urethra, conformal index, and dose nonhomogeneity ratio. The three largest hot spots for the adjusted treatment plan were significantly smaller compared to the clinical treatment plan. The observers preferred the adjusted treatment plan in 132 cases and the clinical in 83 cases. The observers preferred the adjusted treatment plan on homogeneity and organs at risk but preferred the clinical plan on PTV coverage. CONCLUSIONS: Quantitative analysis showed that the postadjustment optimization tool could improve the spatial properties of the treatment plans while maintaining the target coverage.
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