Effects of sex chromosome dosage on corpus callosum morphology in supernumerary sex chromosome aneuploidies.

BackgroundSupernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93), and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20), 47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6).MethodsWe investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex. Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations.ResultsSeveral subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.ConclusionsOur results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups

Human brain mapping: a systematic comparison of parcellation methods for the human cerebral cortex

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously

Atlas construction and spatial normalisation to facilitate radiation-induced late effects research in childhood cancer

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations. In this paper, we investigate the feasibility of atlas construction and spatial normalisation in paediatric radiotherapy. We used planning computed tomography (CT) scans from twenty paediatric patients historically treated with craniospinal irradiation to generate a template CT that is suitable for spatial normalisation. This childhood cancer population representative template was constructed using groupwise image registration. An independent set of 53 subjects from a variety of childhood malignancies was then used to assess the quality of the propagation of new subjects to this common reference space using deformable image registration (i.e., spatial normalisation). The method was evaluated in terms of overall image similarity metrics, contour similarity and preservation of dose-volume properties. After spatial normalisation, we report a dice similarity coefficient of 0.95±0.05, 0.85±0.04, 0.96±0.01, 0.91±0.03, 0.83±0.06 and 0.65±0.16 for brain and spinal canal, ocular globes, lungs, liver, kidneys and bladder. We then demonstrated the potential advantages of an atlas-based approach to study the risk of second malignant neoplasms after radiotherapy. Our findings indicate satisfactory mapping between a heterogeneous group of patients and the template CT. The poorest performance was for organs in the abdominal and pelvic region, likely due to respiratory and physiological motion and to the highly deformable nature of abdominal organs. More specialised algorithms should be explored in the future to improve mapping in these regions. This study is the first step toward voxel-based analysis in radiation-induced toxicities following paediatric radiotherapy

Brain atlas fusion from high-thickness diagnostic magnetic resonance images by learning-based super-resolution

It is fundamentally important to fuse the brain atlas from magnetic resonance (MR) images for many imaging-based studies. Most existing works focus on fusing the atlases from high-quality MR images. However, for low-quality diagnostic images (i.e., with high inter-slice thickness), the problem of atlas fusion has not been addressed yet. In this paper, we intend to fuse the brain atlas from the high-thickness diagnostic MR images that are prevalent for clinical routines. The main idea of our works is to extend the conventional groupwise registration by incorporating a novel super-resolution strategy. The contribution of the proposed super-resolution framework is two-fold. First, each high-thickness subject image is reconstructed to be isotropic by the patch-based sparsity learning. Then, the reconstructed isotropic image is enhanced for better quality through the random-forest-based regression model. In this way, the images obtained by the super-resolution strategy can be fused together by applying the groupwise registration method to construct the required atlas. Our experiments have shown that the proposed framework can effectively solve the problem of atlas fusion from the low-quality brain MR images

Spatial modeling of epidermal nerve fiber patterns

Peripheral neuropathy is a condition associated with poor nerve functionality. Epidermal nerve fiber (ENF) counts per epidermal surface are dramatically reduced and the two-dimensional (2D) spatial structure of ENFs tends to become more clustered as neuropathy progresses. Therefore, studying the spatial structure of ENFs is essential to fully understand the mechanisms that guide those morphological changes. In this article, we compare ENF patterns of healthy controls and subjects suffering from mild diabetic neuropathy by using suction skin blister specimens obtained from the right foot. Previous analysis of these data has focused on the analysis and modeling of the spatial ENF patterns consisting of the points where the nerves enter the epidermis, base points, and the points where the nerve fibers terminate, end points, projected on a 2D plane, regarding the patterns as realizations of spatial point processes. Here, we include the first branching points, the points where the nerve trees branch for the first time, and model the three-dimensional (3D) patterns consisting of these three types of points. To analyze the patterns, spatial summary statistics are used and a new epidermal active territory that measures the volume in the epidermis that is covered by the individual nerve fibers is constructed. We developed a model for both the 2D and the 3D patterns including the branching points. Also, possible competitive behavior between individual nerves is examined. Our results indicate that changes in the ENFs spatial structure can more easily be detected in the later parts of the ENFs

Generative Models for Preprocessing of Hospital Brain Scans

I will in this thesis present novel computational methods for processing routine clinical brain scans. Such scans were originally acquired for qualitative assessment by trained radiologists, and present a number of difficulties for computational models, such as those within common neuroimaging analysis software. The overarching objective of this work is to enable efficient and fully automated analysis of large neuroimaging datasets, of the type currently present in many hospitals worldwide. The methods presented are based on probabilistic, generative models of the observed imaging data, and therefore rely on informative priors and realistic forward models. The first part of the thesis will present a model for image quality improvement, whose key component is a novel prior for multimodal datasets. I will demonstrate its effectiveness for super-resolving thick-sliced clinical MR scans and for denoising CT images and MR-based, multi-parametric mapping acquisitions. I will then show how the same prior can be used for within-subject, intermodal image registration, for more robustly registering large numbers of clinical scans. The second part of the thesis focusses on improved, automatic segmentation and spatial normalisation of routine clinical brain scans. I propose two extensions to a widely used segmentation technique. First, a method for this model to handle missing data, which allows me to predict entirely missing modalities from one, or a few, MR contrasts. Second, a principled way of combining the strengths of probabilistic, generative models with the unprecedented discriminative capability of deep learning. By introducing a convolutional neural network as a Markov random field prior, I can model nonlinear class interactions and learn these using backpropagation. I show that this model is robust to sequence and scanner variability. Finally, I show examples of fitting a population-level, generative model to various neuroimaging data, which can model, e.g., CT scans with haemorrhagic lesions

A Spatiotemporal Volumetric Interpolation Network for 4D Dynamic Medical Image

Dynamic medical imaging is usually limited in application due to the large radiation doses and longer image scanning and reconstruction times. Existing methods attempt to reduce the dynamic sequence by interpolating the volumes between the acquired image volumes. However, these methods are limited to either 2D images and/or are unable to support large variations in the motion between the image volume sequences. In this paper, we present a spatiotemporal volumetric interpolation network (SVIN) designed for 4D dynamic medical images. SVIN introduces dual networks: first is the spatiotemporal motion network that leverages the 3D convolutional neural network (CNN) for unsupervised parametric volumetric registration to derive spatiotemporal motion field from two-image volumes; the second is the sequential volumetric interpolation network, which uses the derived motion field to interpolate image volumes, together with a new regression-based module to characterize the periodic motion cycles in functional organ structures. We also introduce an adaptive multi-scale architecture to capture the volumetric large anatomy motions. Experimental results demonstrated that our SVIN outperformed state-of-the-art temporal medical interpolation methods and natural video interpolation methods that have been extended to support volumetric images. Our ablation study further exemplified that our motion network was able to better represent the large functional motion compared with the state-of-the-art unsupervised medical registration methods.Comment: 10 pages, 8 figures, Conference on Computer Vision and Pattern Recognition (CVPR) 202

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2 , selected using World Health Organization recommendations for growth standards3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5 . The atlas was produced using 1,059 optimal quality, three dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8 . The atlas corresponds structurally to published magnetic resonance images9 , but with finer anatomical details in deep grey matter. The between study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment