Ernst Schwartz

Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis

Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain. Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis. Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality. Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.

Fetal Cerebral Magnetic Resonance Imaging Beyond Morphology.

The recent technological advancement of fast magnetic resonance imaging (MRI) sequences allowed the inclusion of diffusion tensor imaging, functional MRI, and proton MR spectroscopy in prenatal imaging protocols. These methods provide information beyond morphology and hold the key to improving several fields of human neuroscience and clinical diagnostics. Our review introduces the fundamental works that enabled these imaging techniques, and also highlights the most recent contributions to this emerging field of prenatal diagnostics, such as the structural and functional connectomic approach. We introduce the advanced image processing approaches that are extensively used to tackle fetal or maternal movement-related image artifacts, and which are necessary for the optimal interpretation of such imaging data.

Diffeomorphic functional brain surface alignment: Functional demons

&NA; Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro‐anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo‐functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo‐functional dissociation was found in higher association areas compared to primary sensory‐ and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task‐specific core regions. Finally, a comparison of the anatomo‐functional dissociation between cohorts is demonstrated with a group of left and right handed subjects. HighlightsDiffeomorphic functional alignment captures the variability in restingstate connectivity across a population.Alignment of resting‐state connectivity profiles supports task fMRI group analysis.Functional alignment allows to quantify differences between cohorts.

Evaluating deformation patterns of the thoracic aorta in gated CTA sequences

Cardiovascular interventions in the region of the aortic isthmus such as stent-grafting and vessel transposition introduce substantial changes in the deformation properties of the affected vessels. The changes play a fundamental role in the long-term prognosis for any such treatment, but are only poorly understood to date. We explore a fully automated method to quantify the deformation patterns of the thoracic aorta in gated computed tomography sequences. The aorta is segmented by a level set approach that accurately identifies the vessel lumen in each frame of the sequence. Consequently, landmarks on the vessel wall in each frame are registered using a probabilistic method. This allows for the measurement of global and local deformation properties. We evaluate our method on synthetic datasets and report first results of its application on real world data.

Mens inversus in corpore inverso? Language lateralization in a boy with situs inversus totalis

Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror image of default organ position. In this study we picture the co-development between brain and visceral organs in a case of situs inversus totalis from a fetal stage to adolescence and compare our findings to an age-, gender-, and education-matched control with normal position of thoracic and abdominal organs. We show that in this case of situs inversus, functional and structural brain lateralization do not coincide with visceral organ situs. Furthermore, cognitive development in situs inversus is normal. To our knowledge, this is the first report of antenatal cerebral origins of structural and functional brain asymmetry in a case of situs inversus totalis.

A Locally Linear Method for Enforcing Temporal Smoothness in Serial Image Registration

Deformation fields obtained from image registration are commonly used for deriving measurements of morphological changes between reference and follow-up images. As the underlying image matching problem is ill-posed, the exact shape of these deformation fields is often dependent on the regularization method. In longitudinal and cross-sectional studies this effect is amplified if time between acquisitions varies and smoothness between serial deformations is neglected. Existing solutions suffer from high computational costs, strong modeling assumptions and the bias towards a single reference image. In this paper, we propose a computationally efficient solution to this problem via a temporal smoothing formulation in the one-parameter subgroup of diffeomorphisms parametrized by stationary velocity fields. When applied to modeling fetal brain development, the proposed regularization results in smooth deformation fields over time and high data fidelity.

Visualizing changes in vessel wall dynamics due to stent-grafting in the aortic arch

The thoracic aorta is an anatomical structure that is subject to constant motion. Stent-grafting changes the deformation patterns on the vessel surface, and the nature of these changes is suspected to correlate with treatment outcome. However, they are currently only poorly understood. We propose a method for quantifying the changes in vessel motion caused by stent-grafting in the aortic arch. For this, we automatically build a surface model of the vessel and its movement from gated computed tomography sequences that depict the deformation of the thoracic aorta during the cardiac cycle. We reconstruct trajectories corresponding to the displacement of a dense sampling of the vessel surface. From these, we construct a manifold of vessel motion patterns. Models acquired before and after stent-grafting are registered and we analyze the changes to the deformation in the embedding space. Results for four clinical cases indicate that the local density in the embedding space is a marker of local deformation complexity, and sites of potential complications.

Modeling Fetal Cortical Expansion Using Graph-Regularized Gompertz Models

Understanding patterns of brain development before birth is of both high clinical and scientific interest. However, despite advances in reconstruction methods, the challenging setting of in-utero imaging renders precise, point-wise measurements of the rapidly changing fetal brain morphology difficult. This paper proposes a method to deal with bad measurement quality due to image noise, motion artefacts and ensuing segmentation and registration errors by enforcing spatial regularity during the estimation of parametric models of cortical expansion. Qualitative and quantitative analysis of the proposed method was performed on 88 clinical fetal MR volumes. We show that the resulting models accurately capture the morphological and temporal properties of fetal brain development by predicting gestational age on unseen cases at human-level accuracy.

Atypical language representation is unfavorable for language abilities following childhood stroke

Brain plasticity has often been quoted as a reason for the more favorable outcome in childhood stroke compared to adult stroke. We investigated the relationship between language abilities and language localization in childhood stroke. Seventeen children and adolescents with left- or right-sided ischemic stroke and 18 healthy controls were tested with a comprehensive neurolinguistic test battery, and the individual neural representation of language was measured with an fMRI language paradigm. Overall, 12 of 17 stroke patients showed language abilities below average, and five patients exhibited impaired language performance. fMRI revealed increased activity in right hemisphere areas homotopic to left hemisphere language regions. In sum, seven stroke patients revealed atypical, i.e. bilateral or right lateralized language representation. Typical left hemispheric language lateralization was associated with better performance in naming and word fluency, whereas increased involvement of right homologues was accompanied by worse language outcome. In contrast, lesion lateralization or lesion volume did not correlate with language outcome or atypical language lateralization. Thus, atypical language lateralization is unfavorable for language outcome, and right homologues do not have the same cognitive capacity, even in young children.

Tracing the structural origins of atypical language representation: consequences of prenatal mirror-imaged brain asymmetries in a dizygotic twin couple

We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry in a special case of a female dizygotic twin that showed inverted prenatal asymmetry of this structure. For this purpose, we performed a follow-up investigation in this former fetus at the age of seven, where we assessed the functional language lateralization using task-based and resting-state functional magnetic resonance imaging (fMRI). As control group we employed her twin brother, who showed a typical folding pattern prenatally, as well as a complementary set of four age-matched children that had fetal MRI of their brains and typical STS depth asymmetry. We could show that the twin with the atypical fetal asymmetry of the STS also showed significantly differing rightward language lateralization in the frontal and temporal lobes. Additionally, resting-state data suggest a stronger connectivity between inferior frontal gyri in this case. The twin showed normal cognitive development. This result gives a first glimpse into the STS’ atypical asymmetry being a very early morphological marker for later language lateralization.