Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

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

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

Social-sparsity brain decoders: faster spatial sparsity

Spatially-sparse predictors are good models for brain decoding: they give accurate predictions and their weight maps are interpretable as they focus on a small number of regions. However, the state of the art, based on total variation or graph-net, is computationally costly. Here we introduce sparsity in the local neighborhood of each voxel with social-sparsity, a structured shrinkage operator. We find that, on brain imaging classification problems, social-sparsity performs almost as well as total-variation models and better than graph-net, for a fraction of the computational cost. It also very clearly outlines predictive regions. We give details of the model and the algorithm.Comment: in Pattern Recognition in NeuroImaging, Jun 2016, Trento, Italy. 201

Spatio-temporal motion correction and iterative reconstruction of in-utero fetal fMRI

Resting-state functional Magnetic Resonance Imaging (fMRI) is a powerful imaging technique for studying functional development of the brain in utero. However, unpredictable and excessive movement of fetuses have limited its clinical applicability. Previous studies have focused primarily on the accurate estimation of the motion parameters employing a single step 3D interpolation at each individual time frame to recover a motion-free 4D fMRI image. Using only information from a 3D spatial neighborhood neglects the temporal structure of fMRI and useful information from neighboring timepoints. Here, we propose a novel technique based on four dimensional iterative reconstruction of the motion scattered fMRI slices. Quantitative evaluation of the proposed method on a cohort of real clinical fetal fMRI data indicates improvement of reconstruction quality compared to the conventional 3D interpolation approaches.Comment: Accepted by MICCAI 202

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

Fetal Brain Biometric Measurements on 3D Super-Resolution Reconstructed T2-Weighted MRI: An Intra- and Inter-observer Agreement Study.

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18-34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland-Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume