Geodesic Information Flows: Spatially-Variant Graphs and Their Application to Segmentation and Fusion

Clinical annotations, such as voxel-wise binary or probabilistic tissue segmentations, structural parcellations, pathological regionsof- interest and anatomical landmarks are key to many clinical studies. However, due to the time consuming nature of manually generating these annotations, they tend to be scarce and limited to small subsets of data. This work explores a novel framework to propagate voxel-wise annotations between morphologically dissimilar images by diffusing and mapping the available examples through intermediate steps. A spatially-variant graph structure connecting morphologically similar subjects is introduced over a database of images, enabling the gradual diffusion of information to all the subjects, even in the presence of large-scale morphological variability. We illustrate the utility of the proposed framework on two example applications: brain parcellation using categorical labels and tissue segmentation using probabilistic features. The application of the proposed method to categorical label fusion showed highly statistically significant improvements when compared to state-of-the-art methodologies. Significant improvements were also observed when applying the proposed framework to probabilistic tissue segmentation of both synthetic and real data, mainly in the presence of large morphological variability

Modeling the structure of multivariate manifolds: Shape maps

We propose a shape population metric that reflects the interdependencies between points observed in a set of examples. It provides a notion of topology for shape and appearance models that represents the behavior of individual observations in a metric space, in which distances between points correspond to their joint modeling properties. A Markov chain is learnt using the description lengths of models that describe sub sets of the entire data. The according diffusion map or shape map provides for the metric that reflects the behavior of the training population. With this metric functional clustering, deformation- or motion segmentation, sparse sampling and the treatment of outliers can be dealt with in a unified and transparent manner. We report experimental results on synthetic and real world data and compare the framework with existing specialized approaches. 1

A normative spatiotemporal MRI atlas of the fetal brain for automatic segmentation and analysis of early brain growth.

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth

Bayesian generative learning of brain and spinal cord templates from neuroimaging datasets

In the field of neuroimaging, Bayesian modelling techniques have been largely adopted and recognised as powerful tools for the purpose of extracting quantitative anatomical and functional information from medical scans. Nevertheless the potential of Bayesian inference has not yet been fully exploited, as many available tools rely on point estimation techniques, such as maximum likelihood estimation, rather than on full Bayesian inference. The aim of this thesis is to explore the value of approximate learning schemes, for instance variational Bayes, to perform inference from brain and spinal cord MRI data. The applications that will be explored in this work mainly concern image segmentation and atlas construction, with a particular emphasis on the problem of shape and intensity prior learning, from large training data sets of structural MR scans. The resulting computational tools are intended to enable integrated brain and spinal cord morphometric analyses, as opposed to the approach that is most commonly adopted in neuroimaging, which consists in optimising separate tools for brain and spine morphometrics

Automated morphometry for mouse brain MRI through structural parcellation and thickness estimation

Quantitative morphometric analysis is an important tool in neuroimaging for the study of understanding the physiology of development, normal aging, disease pathology and treatment effect. However, compared to clinical study, image analysis methods specific to preclinical neuroimaging are still lacking. The aim of this PhD thesis is to achieve automatic quantitative structural analysis of mouse brain MRI. This thesis focuses on two quantitative methods which have been widely accepted as quantitative imaging biomarkers: brain structure segmentation and cortical thickness estimation. Firstly, a multi-atlas based structural parcellation framework has been constructed, which incorporates preprocessing steps such as intensity non-uniformity correction and multi-atlas based brain extraction, followed by non-rigid registration and local weighted multi-atlas label fusion. Validation of the framework demonstrated improved performance compared to single-atlas-based structural parcellation, as well as to global weighted multi-atlas label fusion methods. The framework has been further applied to in vivo and ex vivo data acquired from the same cohort so that the respective volumetric analysis can be compared. The results reveal a non-uniform distribution of volume changes from the in vivo to the post-mortem brain. In addition, volumetric analysis based on the segmented structures showed similar statistical power on in vivo or ex vivo data within the same cohort. Secondly, a framework to segment the mouse cerebellar cortex sublayers from brain MRI data and estimate the thickness of the corresponding layers has been developed. Application of the framework on the experimental data demonstrated its ability to distinguish sublayer thickness variation between transgenic strains and their wild-type littermate, which cannot be detected using full cortical thickness measurements alone. In conclusion, two quantitative morphometric analysis frameworks have been pre-sented in this thesis. This demonstrated the successful application of translational quantitative methods to preclinical mouse brain MRI

Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32)

The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.Fil: Falquez, Rosalux. University of Heidelberg; AlemaniaFil: Couto, Juan Blas Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Freitag, Martin T.. German Cancer Research Center; AlemaniaFil: Berger, Moritz. German Cancer Research Center; AlemaniaFil: Arens, Elisabeth A.. University of Heidelberg; AlemaniaFil: Lang, Simone. University of Heidelberg; AlemaniaFil: Barnow, Sven. University of Heidelberg; Alemani