Multimodality and Nonrigid Image Registration with Application to Diffusion Tensor Imaging

The great challenge in image registration is to devise computationally efficient algorithms for aligning images so that their details overlap accurately. The first problem addressed in this thesis is multimodality medical image registration, which we formulate as an optimization problem in the information-theoretic setting. We introduce a viable and practical image registration method by maximizing a generalized entropic dissimilarity measure using a modified simultaneous perturbation stochastic approximation algorithm. The feasibility of the proposed image registration approach is demonstrated through extensive experiments. The rest of the thesis is devoted to nonrigid medical image registration. We propose an informationtheoretic framework by optimizing a non-extensive entropic similarity measure using the quasi-Newton method as an optimization scheme and cubic B-splines for modeling the nonrigid deformation field between the fixed and moving 3D image pairs. To achieve a compromise between the nonrigid registration accuracy and the associated computational cost, we implement a three-level hierarchical multi-resolution approach in such a way that the image resolution is increased in a coarse to fine fashion. The feasibility and registration accuracy of the proposed method are demonstrated through experimental results on a 3D magnetic resonance data volume and also on clinically acquired 4D computed tomography image data sets. In the same vein, we extend our nonrigid registration approach to align diffusion tensor images for multiple components by enabling explicit optimization of tensor reorientation. Incorporating tensor reorientation in the registration algorithm is pivotal in wrapping diffusion tensor images. Experimental results on diffusion-tensor image registration indicate the feasibility of the proposed approach and a much better performance compared to the affine registration method based on mutual information, not only in terms of registration accuracy in the presence of geometric distortions but also in terms of robustness in the presence of Rician noise

Use of Multicomponent Non-Rigid Registration to Improve Alignment of Serial Oncological PET/CT Studies

Non-rigid registration of serial head and neck FDG PET/CT images from a combined scanner can be problematic. Registration techniques typically rely on similarity measures calculated from voxel intensity values; CT-CT registration is superior to PET-PET registration due to the higher quality of anatomical information present in this modality. However, when metal artefacts from dental fillings are present in a pair of CT images, a nonrigid registration will incorrectly attempt to register the two artefacts together since they are strong features compared to the features that represent the actual anatomy. This leads to localised registration errors in the deformation field in the vicinity of the artefacts. Our objective was to develop a registration technique which overcomes these limitations by using combined information from both modalities. To study the effect of artefacts on registration, metal artefacts were simulated with one CT image rotated by a small angle in the sagittal plane. Image pairs containing these simulated artifacts were then registered to evaluate the resulting errors. To improve the registration in the vicinity where there were artefacts, intensity information from the PET images was incorporated using several techniques. A well-established B-splines based non-rigid registration code was reworked to allow multicomponent registration. A similarity measure with four possible weighted components relating to the ways in which the CT and PET information can be combined to drive the registration of a pair of these dual-valued images was employed. Several registration methods based on using this multicomponent similarity measure were implemented with the goal of effectively registering the images containing the simulated artifacts. A method was also developed to swap control point displacements from the PET-derived transformation in the vicinity of the artefact. This method yielded the best result on the simulated images and was evaluated on images where actual dental artifacts were present

White matter microstructure and atypical visual orienting in 7 month-olds at risk for autism

pre-printObjective: The authors sought to determine whether specific patterns of oculo-motor functioning and visual orientingcharacterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors. Method:Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low- risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal path-ways and the splenium and genu of the corpus callosum. Results: Visual orienting latencies were longer in 7-month-old infants who ex-pressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD. Conclusions: Flexiblyandef ficientlyorienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis

Age-related microstructural differences quantified using myelin water imaging and advanced diffusion MRI

Age-related microstructural differences have been detected using diffusion tensor imaging (DTI). Although DTI is sensitive to the effects of aging, it is not specific to any underlying biological mechanism, including demyelination. Combining multiexponential T2 relaxation (MET2) and multishell diffusion MRI (dMRI) techniques may elucidate such processes. Multishell dMRI and MET2 data were acquired from 59 healthy participants aged 17-70 years. Whole-brain and regional age-associated correlations of measures related to multiple dMRI models (DTI, diffusion kurtosis imaging [DKI], neurite orientation dispersion and density imaging [NODDI]) and myelin-sensitive MET2 metrics were assessed. DTI and NODDI revealed widespread increases in isotropic diffusivity with increasing age. In frontal white matter, fractional anisotropy linearly decreased with age, paralleled by increased "neurite" dispersion and no difference in myelin water fraction. DKI measures and neurite density correlated well with myelin water fraction and intracellular and extracellular water fraction. DTI estimates remain among the most sensitive markers for age-related alterations in white matter. NODDI, DKI, and MET2 indicate that the initial decrease in frontal fractional anisotropy may be due to increased axonal dispersion rather than demyelination

White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism

The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors

Separating fetal and maternal placenta circulations using multi-parametric MRI

Purpose The placenta is a vital organ for the exchange of oxygen, nutrients, and waste products between fetus and mother. The placenta may suffer from several pathologies, which affect this fetal‐maternal exchange, thus the flow properties of the placenta are of interest in determining the course of pregnancy. In this work, we propose a new multiparametric model for placental tissue signal in MRI. Methods We describe a method that separates fetal and maternal flow characteristics of the placenta using a 3‐compartment model comprising fast and slowly circulating fluid pools, and a tissue pool is fitted to overlapping multiecho T2 relaxometry and diffusion MRI with low b‐values. We implemented the combined model and acquisition on a standard 1.5 Tesla clinical system with acquisition taking less than 20 minutes. Results We apply this combined acquisition in 6 control singleton placentas. Mean myometrial T2 relaxation time was 123.63 (±6.71) ms. Mean T2 relaxation time of maternal blood was 202.17 (±92.98) ms. In the placenta, mean T2 relaxation time of the fetal blood component was 144.89 (±54.42) ms. Mean ratio of maternal to fetal blood volume was 1.16 (±0.6), and mean fetal blood saturation was 72.93 (±20.11)% across all 6 cases. Conclusion The novel acquisition in this work allows the measurement of histologically relevant physical parameters, such as the relative proportions of vascular spaces. In the placenta, this may help us to better understand the physiological properties of the tissue in disease

Characterising population variability in brain structure through models of whole-brain structural connectivity

Models of whole-brain connectivity are valuable for understanding neurological function. This thesis seeks to develop an optimal framework for extracting models of whole-brain connectivity from clinically acquired diffusion data. We propose new approaches for studying these models. The aim is to develop techniques which can take models of brain connectivity and use them to identify biomarkers or phenotypes of disease. The models of connectivity are extracted using a standard probabilistic tractography algorithm, modified to assess the structural integrity of tracts, through estimates of white matter anisotropy. Connections are traced between 77 regions of interest, automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. The estimates of tissue integrity for each tract are input as indices in 77x77 ”connectivity” matrices, extracted for large populations of clinical data. These are compared in subsequent studies. To date, most whole-brain connectivity studies have characterised population differences using graph theory techniques. However these can be limited in their ability to pinpoint the locations of differences in the underlying neural anatomy. Therefore, this thesis proposes new techniques. These include a spectral clustering approach for comparing population differences in the clustering properties of weighted brain networks. In addition, machine learning approaches are suggested for the first time. These are particularly advantageous as they allow classification of subjects and extraction of features which best represent the differences between groups. One limitation of the proposed approach is that errors propagate from segmentation and registration steps prior to tractography. This can cumulate in the assignment of false positive connections, where the contribution of these factors may vary across populations, causing the appearance of population differences where there are none. The final contribution of this thesis is therefore to develop a common co-ordinate space approach. This combines probabilistic models of voxel-wise diffusion for each subject into a single probabilistic model of diffusion for the population. This allows tractography to be performed only once, ensuring that there is one model of connectivity. Cross-subject differences can then be identified by mapping individual subjects’ anisotropy data to this model. The approach is used to compare populations separated by age and gender