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Cardiac magnetic resonance (CMR) is used extensively in the diagnosis and management of cardiovascular disease. Deep learning methods have proven to deliver segmentation results comparable to human experts in CMR imaging, however, no successful attempts have been made at fully automated diagnosis. This has been contributed to a lack of sufficiently large datasets required for end-to-end learning of diagnoses. Here we propose to exploit the excellent results obtained in segmentation by jointly training with diagnosis in a multitask learning setting. We hypothesize that segmentation has a regularizing effect on learning and promotes learning of features relevant for diagnosis. Results show a three-fold reduction of the classification error to 0.12 compared to a baseline without segmentation, both results are obtained by training on just 75 cases in a dataset (ACDC) that is equally distributed over 5 classes.

Biomedical Engineering

Advisors/Committee Members: Niessen, Wiro (mentor), Verjans, Johan (mentor), Carneiro, Gustavo (mentor), Delft University of Technology (degree granting institution).

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Prostate cancer is a disease with very high prevalence and mortality in the western world. An early accurate diagnosis can increase treatment efficiency. Current diagnosing techniques consist in systematic biopsy sampling. Radiomics can infer tumor's phenotypic differentiations from medical images, providing an accurate guide for biopsy sampling and making personalized treatment plans possible. Radiomics are various features that are extracted from medical images. Subsequently they are applied to train machine learning models that distinguish between healthy or cancerous tissue. In this thesis a software routine that extracts the most commonly reported MRI prostate cancer radiomic features was built. Then, several classification methods were tried. Results were validated on T2 MRI patient images with confirmed histopathology from two different clinics.

Biomedical Engineering

Advisors/Committee Members: Niessen, Wiro (mentor), Veenland, Jifke (mentor), Delft University of Technology (degree granting institution).

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Patients with 1p/19q co-deleted low grade glioma (LGGs) have better prognosis and react better to certain treatments than patients with intact 1p/19q LGG. Currently, information about the 1p/19q co-deletion status is obtained by means of an invasive procedure called biopsy. As an alternative, non-invasive techniques to extract this information from medical images are being studied. Recent research suggests that local binary patterns (LBPs), a textural image descriptor, are an important feature which can predict the 1p/19q co-deletion from MRI scans. In this project we report the effect of including LBP information in a convolutional neural network (CNN) to predict the 1p/19q co-deletion status in patients suffering from a presumed LGG using pre-operative MRI scans. A combination of convolutional filters was designed and included in the CNN, resulting into local binary convolutional neural networks (LBCNNs). Three LBP descriptors, each of them representing a different textural scale, were studied, as well as the combination of the three. A default CNN without LBPs was also studied. To validate the designed filters and to study more sophisticated LBPs images like the uniform LBPs, pre-computed LBP images were directly input to the CNN. An in-house multi-institution MRI dataset consisting of 284 patients who had undergone a biopsy or resection before the treatment, and with available pre-operative T1-weighted post contrast and T2-weighted scans was used to train the different network architectures. An independent dataset consisting of 129 patients was used to validate the results. The performance of the LBCNNs was compared to the performance of the CNN. The performance of the CNN and LBCNNs was similar, reporting an area under the receiver operating characteristic curve (AUC) ranging from 0.816 to 0.872 for the different architectures. These findings suggest that the CNN can extract information relative to LBPs by itself. In addition, pre-computed uniform LBPs report similar metrics (AUC: 0.819), suggesting that they do not add new information.

Mechanical Engineering

Advisors/Committee Members: Niessen, Wiro (mentor), Klein, Stefan (mentor), Van Der Voort, Sebastian R. (mentor), Delft University of Technology (degree granting institution).

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Cardiovascular diseases and stroke are currently the leading causes of death worldwide. Atherosclerotic plaque is a mostly asymptotic vascular disease, but rupture of an atherosclerotic plaque in the carotid artery could lead to stroke. Automated segmentation of plaque components could help improve risk assessment by producing fast and reliable results while saving costs. In this thesis two extensive comparisons have been made. First supervised classifiers are compared in the pixel-wise segmentation task of plaque components. In this comparison five conventional machine learning techniques and one deep learning architecture have been evaluated: linear and quadratic Bayes normal classifiers, linear logistic classifier, random forest and a U-net architecture. In the second comparison classifiers are evaluated in a detection task for their ability to learn with weakly labelled data. This is done within the multiple instance learning (MIL) framework. In addition to conventional multiple instance learning algorithms, a new MIL adaptation of the deep learning architecture, MIL U-net, is proposed and evaluated. In the pixel-wise segmentation tasks the U-net architecture was the best overall classifier after the addition of 93 extra training patients to the original 20 training patients. A good inter-rater agreement was found for the haemorrhage class (ICC = 0.684) and the calcification class (ICC = 0.627). In the detection task the supervised methods, trained with one-sided noise, outperformed multiple instance classifiers such as MIL-Boost and the proposed MIL U-net. In this task both random forest and the linear logistic classifier obtained a fair Cohen's kappa (0.419 and 0.445 respectively) for detection of calcification per slice. The same classifiers obtained good correlation (Cohen's kappa 0.717 and 0.666 respectively) for haemorrhage detection per slice.

Mechanical Engineering

Advisors/Committee Members: de Bruijne, Marleen (mentor), Sedghi Gamechi, Zahra (mentor), Niessen, Wiro (graduation committee), Kooij, Julian (graduation committee), Delft University of Technology (degree granting institution).

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The gap between predicted brain age and chronological age could serve as biomarker for early-stage neurodegeneration and as potentially as a risk indicator for dementia. We assess the utility of this age gap as a risk biomarker for incident dementia in a general elderly population. The brain age is estimated from longitudinal brain magnetic resonance imaging (MRI) data using deep learning models. From the population-based Rotterdam Study, 5656 dementia-free and stroke-free participants (mean age 64.67±9.82, 54.73% women) underwent brain MRI at 1.5T, including three-dimensional (3D) T1-weighted sequence, between 2006 and 2015. All participants were followed for incident dementia until 2016. During 6.66±2.46 years of follow-up, 159 subjects developed dementia. The entire dataset was split into control (N=5497) and incident dementia (N=159) groups. We then built a convolutional neural network (CNN) model trained on the control group to predict brain age based on brain MRI. Model prediction performance was measured in mean absolute error MAE=4.45±3.59 years of brain age prediction. Reproducibility of prediction was tested using the intra-class correlation coefficient ICC=0.97 (95% confidence interval CI=0.96-0.98), computed on a subset of 80 subjects. Hereafter, we investigated the gap between model predicted age and chronological age of the incident dementia group data, compared to control group. Logistic regressions and Cox proportional hazards models were used to assess the association of the age gap with incident dementia, adjusted for years of education, ApoE4 allele carriership, GM and intracranial volume. These models showed that the age gap was significantly related to incident dementia (odds ratio OR=1.11 and 95% confidence intervals CI=1.05-1.16; hazard ratio HR=1.11 and 95% CI=1.06-1.15, respectively). Additionally, we computed the attention maps of CNN, which shows the importance of brain regions for age prediction. These were particularly focused on the amygdalae and hippocampi. We show that the gap between predicted and chronological brain age is a biomarker, associated with a risk of dementia development. This suggests that it can potentially be used as a complimentary biomarker for early-stage dementia risk screening.

Mechanical Engineering

Advisors/Committee Members: Niessen, Wiro (mentor), Kooij, Julian (graduation committee), Vos, Frans (graduation committee), Roshchupkin, Gennady V. (graduation committee), Delft University of Technology (degree granting institution).

▼ Perivascular spaces (PVS) visible on MRI are currently emerging as an important potential neuroimaging marker for several pathologies in the brain like Alzheimer’s disease and cerebral small vessel disease. PVS are fluid-filled spaces surrounding vessels as they enter the brain. Although PVS are normally not noticeable on MRI scans acquired at clinical field strengths, when these spaces increase in size they become increasingly visible and quantifiable. To study these spaces it is important to have a robust method for quantifying PVS. Manual quantification of PVS is challenging, time-consuming and subject to observer bias due to the difficulty of distinguishing PVS from mimics and the large number of PVS that can occur in MRI scans. Many promising (semi-)automated methods have been proposed recently to decrease annotation time and intra- and inter-observer variability while providing more information about EPVS. However there are still various limitations in the current methods that need to be overcome. An important limitation is that most of the methods are based on elaborate preprocessing steps, feature extraction and heuristic fine-tuning of parameters, making the use of these methods on new datasets cumbersome. Furthermore the majority of the currently proposed methods have been evaluated on small sets of barely 30 images, as most of these methods aim to segment PVS and require voxel-wise annotations for evaluation. In this thesis we propose a method for automated detection of perivascular spaces that combines a convolutional neural network and geodesic distance transform (GDT). We propose to use dot annotations instead of voxel-wise segmentations as this is less time-consuming than fully segmenting PVS while still providing the location of PVS. This enables us to use a considerably larger dataset with ground truth locations than is used in all previously proposed (semi-)automatic methods that provide the location of PVS. We investigated two approaches of using geodesic distance transform to optimize the CNN to detect PVS. The first approach focuses on optimizing the CNN for voxel-wise regression of the geodesic distance map (GDM) computed from the dots and the intensity image. The second approach aims to predict segmentations of the PVS using a CNN that is trained on approximated segmentations obtained by thresholding GDMs. We use 1202 proton density-weighted (PDw) MRI scans to develop our methods and 1000 other scans are used to evaluate the performance of the methods. We show that our methods match human intra-rater performance on detecting PVS without the need for any user interaction. Additionally we show that GDMs are extremely useful for capturing complex morphologies when computed from dot annotations. Our experiments indicate that GDMs can be used to provide valuable additional information to CNNs during training. Advisors/Committee Members: Dubost, Florian (mentor), de Bruijne, Marleen (mentor), Niessen, Wiro (graduation committee), Vos, Frans (graduation committee), Vilanova Bartroli, Anna (graduation committee), Staring, Marius (graduation committee), Delft University of Technology (degree granting institution).