MRI Super-Resolution using Multi-Channel Total Variation

This paper presents a generative model for super-resolution in routine clinical magnetic resonance images (MRI), of arbitrary orientation and contrast. The model recasts the recovery of high resolution images as an inverse problem, in which a forward model simulates the slice-select profile of the MR scanner. The paper introduces a prior based on multi-channel total variation for MRI super-resolution. Bias-variance trade-off is handled by estimating hyper-parameters from the low resolution input scans. The model was validated on a large database of brain images. The validation showed that the model can improve brain segmentation, that it can recover anatomical information between images of different MR contrasts, and that it generalises well to the large variability present in MR images of different subjects. The implementation is freely available at https://github.com/brudfors/spm_superre

Volumetric MRI Reconstruction from 2D Slices in the Presence of Motion

Despite recent advances in acquisition techniques and reconstruction algorithms, magnetic resonance imaging (MRI) remains challenging in the presence of motion. To mitigate this, ultra-fast two-dimensional (2D) MRI sequences are often used in clinical practice to acquire thick, low-resolution (LR) 2D slices to reduce in-plane motion. The resulting stacks of thick 2D slices typically provide high-quality visualizations when viewed in the in-plane direction. However, the low spatial resolution in the through-plane direction in combination with motion commonly occurring between individual slice acquisitions gives rise to stacks with overall limited geometric integrity. In further consequence, an accurate and reliable diagnosis may be compromised when using such motion-corrupted, thick-slice MRI data. This thesis presents methods to volumetrically reconstruct geometrically consistent, high-resolution (HR) three-dimensional (3D) images from motion-corrupted, possibly sparse, low-resolution 2D MR slices. It focuses on volumetric reconstructions techniques using inverse problem formulations applicable to a broad field of clinical applications in which associated motion patterns are inherently different, but the use of thick-slice MR data is current clinical practice. In particular, volumetric reconstruction frameworks are developed based on slice-to-volume registration with inter-slice transformation regularization and robust, complete-outlier rejection for the reconstruction step that can either avoid or efficiently deal with potential slice-misregistrations. Additionally, this thesis describes efficient Forward-Backward Splitting schemes for image registration for any combination of differentiable (not necessarily convex) similarity measure and convex (not necessarily smooth) regularization with a tractable proximal operator. Experiments are performed on fetal and upper abdominal MRI, and on historical, printed brain MR films associated with a uniquely long-term study dating back to the 1980s. The results demonstrate the broad applicability of the presented frameworks to achieve robust reconstructions with the potential to improve disease diagnosis and patient management in clinical practice

Comparison of Super Resolution Reconstruction Acquisition Geometries for Use in Mouse Phenotyping

3D isotropic imaging at high spatial resolution (30–100 microns) is important for comparing mouse phenotypes. 3D imaging at high spatial resolutions is limited by long acquisition times and is not possible in many in vivo settings. Super resolution reconstruction (SRR) is a postprocessing technique that has been proposed to improve spatial resolution in the slice-select direction using multiple 2D multislice acquisitions. Any 2D multislice acquisition can be used for SRR. In this study, the effects of using three different low-resolution acquisition geometries (orthogonal, rotational, and shifted) on SRR images were evaluated and compared to a known standard. Iterative back projection was used for the reconstruction of all three acquisition geometries. The results of the study indicate that super resolution reconstructed images based on orthogonally acquired low-resolution images resulted in reconstructed images with higher SNR and CNR in less acquisition time than those based on rotational and shifted acquisition geometries. However, interpolation artifacts were observed in SRR images based on orthogonal acquisition geometry, particularly when the slice thickness was greater than six times the inplane voxel size. Reconstructions based on rotational geometry appeared smoother than those based on orthogonal geometry, but they required two times longer to acquire than the orthogonal LR images

Joint registration and synthesis using a probabilistic model for alignment of MRI and histological sections

Nonlinear registration of 2D histological sections with corresponding slices of MRI data is a critical step of 3D histology reconstruction. This task is difficult due to the large differences in image contrast and resolution, as well as the complex nonrigid distortions produced when sectioning the sample and mounting it on the glass slide. It has been shown in brain MRI registration that better spatial alignment across modalities can be obtained by synthesizing one modality from the other and then using intra-modality registration metrics, rather than by using mutual information (MI) as metric. However, such an approach typically requires a database of aligned images from the two modalities, which is very difficult to obtain for histology/MRI. Here, we overcome this limitation with a probabilistic method that simultaneously solves for registration and synthesis directly on the target images, without any training data. In our model, the MRI slice is assumed to be a contrast-warped, spatially deformed version of the histological section. We use approximate Bayesian inference to iteratively refine the probabilistic estimate of the synthesis and the registration, while accounting for each other's uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in the framework for increased performance. Experiments on a synthetic dataset show that, compared with MI, the proposed method makes it possible to use a much more flexible deformation model in the registration to improve its accuracy, without compromising robustness. Moreover, our framework also exploits information in manually placed landmarks more efficiently than MI, since landmarks inform both synthesis and registration - as opposed to registration alone. Finally, we show qualitative results on the public Allen atlas, in which the proposed method provides a clear improvement over MI based registration

MRI super-resolution using multi-channel total variation

This paper presents a generative model for super-resolution in routine clinical magnetic resonance images (MRI), of arbitrary orientation and contrast. The model recasts the recovery of high resolution images as an inverse problem, in which a forward model simulates the slice-select profile of the MR scanner. The paper introduces a prior based on multi-channel total variation for MRI super-resolution. Bias-variance trade-off is handled by estimating hyper-parameters from the low resolution input scans. The model was validated on a large database of brain images. The validation showed that the model can improve brain segmentation, that it can recover anatomical information between images of different MR contrasts, and that it generalises well to the large variability present in MR images of different subjects

A Fetal Brain magnetic resonance Acquisition Numerical phantom (FaBiAN)

Accurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Bridging generative models and Convolutional Neural Networks for domain-agnostic segmentation of brain MRI

Segmentation of brain MRI scans is paramount in neuroimaging, as it is a prerequisite for many subsequent analyses. Although manual segmentation is considered the gold standard, it suffers from severe reproducibility issues, and is extremely tedious, which limits its application to large datasets. Therefore, there is a clear need for automated tools that enable fast and accurate segmentation of brain MRI scans. Recent methods rely on convolutional neural networks (CNNs). While CNNs obtain accurate results on their training domain, they are highly sensitive to changes in resolution and MRI contrast. Although data augmentation and domain adaptation techniques can increase the generalisability of CNNs, these methods still need to be retrained for every new domain, which requires costly labelling of images. Here, we present a learning strategy to make CNNs agnostic to MRI contrast, resolution, and numerous artefacts. Specifically, we train a network with synthetic data sampled from a generative model conditioned on segmentations. Crucially, we adopt a domain randomisation approach where all generation parameters are drawn for each example from uniform priors. As a result, the network is forced to learn domain-agnostic features, and can segment real test scans without retraining. The proposed method almost achieves the accuracy of supervised CNNs on their training domain, and substantially outperforms state-of-the-art domain adaptation methods. Finally, based on this learning strategy, we present a segmentation suite for robust analysis of heterogeneous clinical scans. Overall, our approach unlocks the development of morphometry on millions of clinical scans, which ultimately has the potential to improve the diagnosis and characterisation of neurological disorders

Novel Image Processing Methods for Improved Fetal Brain MRI

Fetal magnetic resonance imaging (MRI) has been increasingly used as a powerful complement imaging modality to ultrasound imaging (US) for the clinical evaluation of prenatal abnormalities. Specifically, clinical application of fetal MRI has been significantly improved in the nineties by hardware and software advances with the development of ultrafast multi-slice T2-weighted (T2w) acquisition sequences able to freeze the unpredictable fetal motion and provide excellent soft-tissue contrast. Fetal motion is indeed the major challenge in fetal MRI and slice acquisition time should be kept as short as possible. As a result, typical fetal MRI examination involves the acquisition of a set of orthogonally planned scans of thick two-dimensional slices, largely free of intra-slice motion artifacts. The poor resolution in the slice-select dimension as well as possible motion occurring between slices limits further quantitative data analysis, which is the key for a better understanding of the developing brain but also the key for the determination of operator-independent biomarkers that might significantly facilitate fetal diagnosis and prognosis. To this end, several research groups have developed in the past ten years advanced image processing methods, often denoted by motion-robust super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) scans, a high-resolution (HR) motion-free volume. SR problem is usually modeled as a linear inverse problem describing the imaging degradation due to acquisition and fetal motion. Typically, such approaches consist in iterating between slice motion estimation that estimates the motion parameters and SR that recovers the HR image given the estimated degradation model. This thesis focuses on the development of novel advanced image processing methods, which have enabled the design of a completely automated reconstruction pipeline for fetal MRI. The proposed techniques help in improving state-of-the-art fetal MRI reconstruction in terms of efficiency, robustness and minimized user-interactions, with the ultimate goal of being translated to the clinical environment. The first part focuses on the development of a more efficient Total Variation (TV)-regularized optimization algorithm for the SR problem. The algorithm uses recent advances in convex optimization with a novel adaptive regularization strategy to offer simultaneously fast, accurate and robust solutions to the fetal image recovery problem. Extensive validations on both simulated fetal and real clinical data show the proposed algorithm is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods. The second part focuses on the development of a novel automatic brain localization and extraction approach based on template-to-slice block matching and deformable slice-totemplate registration. Asmost fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant voxels of low-resolution (LR) images to enhance the quality of inter-slice motion correction and image reconstruction, the fetal brain needs to be localized and extracted as a first step. These tasks generally necessitate user interaction, manually or semi-automatically done. Our methods have enabled the design of completely automated reconstruction pipeline that involves intensity normalization, inter-slice motion estimation, and super-resolution. Quantitative evaluation on clinical MRI scans shows that our approach produces brain masks that are very close to manually drawn brain masks, and ratings performed by two expert observers show that the proposed pipeline achieves similar reconstruction quality to reference reconstruction based on manual slice-by-slice brain extraction without any further effort. The third part investigates the possibility of automatic cortical folding quantification, one of the best biomarkers of brain maturation, by combining our automatic reconstruction pipeline with a state-of-the-art fetal brain tissue segmentation method and existing automated tools provided for adult brain’s cortical folding quantification. Results indicate that our reconstruction pipeline can provide HR MR images with sufficient quality that enable the use of surface tessellation and active surface algorithms similar to those developed for adults to extract meaningful information about fetal brain maturation. Finally, the last part presents new methodological improvements of the reconstruction pipeline aiming at improving the quality of the image for quantitative data analysis, whose accuracy is highly dependent on the quality and resolution of the reconstructed image. In particular, it presents a more consistent and global magnetic bias field correction method which takes advantage of the super-resolution framework to provide a final reconstructed image quasi free of the smooth bias field. Then, it presents a new TV SR algorithm that uses the Huber norm in the data fidelity term to be more robust to non-Gaussian outliers. It also presents the design of a novel joint reconstruction-segmentation framework and the development of a novel TV SR algorithm driven by segmentation to produce images with enhanced edge information that could ultimately improve their segmentation. Finally, it preliminary investigates the capability of increasing the resolution in the in-plane dimensions using SR to ultimately reduce the partial volume effect