Biology subjects

Tuura, R.

Publications and source records attributed to Tuura, R..

8 recordsLinked to original sources

bioRxiv2025

Atlas-independent brain connectome analysis at voxel-level granularity: graph convolutional networks for etiology classification in newborns

Early identification of altered brain networks in neonates at risk for neurodevelopmental impairments is critical for timely intervention and improving outcomes. This study explores the potential of graph convolutional networks (GCNs) applied to structural brain connectomes at the voxel level granularity to classify neonatal connectomes by their underlying etiology: 51 children with congenital heart disease (CHD), 100 children born very preterm (PB), and 43 children with spina bifida aperta (SBA). Leveraging the flexibility of voxel-level parcellation, we captured fine-grained connectomic differences that improved classification performance (F1 = 0.78) compared to both atlas-based methods (F1 = 0.62) and a multilayer perceptron baseline model (F1 = 0.69). This approach enables subject-specific parcellation without the need for predefined anatomical templates, facilitating the analysis of diverse brain morphologies and age ranges. Attribution analysis using integrated gradients provided interpretable insights into etiology-specific connectomic patterns, highlighting regions of potential neurodevelopmental importance, such as the Rolandic operculum, inferior parietal lobule, and inferior frontal gyrus. Lateralized attribution patterns in PB reflected known neurodevelopmental alterations, underscoring the value of interpretable graph learning for understanding etiology-specific connectomic features. This work represents an important step toward atlas-independent connectome analysis, offering a novel framework for studying diverse neonatal populations and advancing our understanding of early brain development.

neuroscience↗

bioRxiv2024

Developmental trajectory of thalamus topography during the late preterm and perinatal period in normal development, after premature birth and in congenital heart defects

The thalamus plays a critical role in neural circuit maturation and brain connectivity. It is well known to show a characteristic topographical organization of local and long-range connectivity, yet developmental changes in this topography remains incompletely understood. Our study aims to first validate the use of diffusion MRI for the topographic delineation of thalamic subdivisions (nuclei), to characterize thalamic topography during development and assess the impact of congenital heart defects (CHD) on thalamus development. We used local fiber orientation distribution functions, derived from diffusion MRI (dMRI) data, to subdivide the thalamus into seven clusters. We first evaluated the within-subject reproducibility of a dMRI based clustering method across 30 adults scan-rescan datasets (n = 30) using K-means clustering, achieving reproducible segmentation of the thalamus into seven parts. This was applied to a large developmental cohort comprising normally developing infants from the term-born dHCP cohort (n = 68, gestational age [GW] at MRI scan ranging from 37.4 to 44.8 weeks, mean {+/-} SD: 41.4 {+/-} 2.1 weeks) and the Zurich cohort (n = 42, GW at MRI ranging from 39.0 to 48.7 weeks, mean {+/-} SD: 42.55 {+/-} 1.96 weeks). The cohort also included preterm-born dHCP cohort (n = 48, GW at MRI scan ranging from 29.3 to 37.4 corrected gestational weeks, mean {+/-} SD: 34.4 {+/-} 2.02 weeks) and one case of a postmortem fetal specimen (n = 1, GW at MRI = 21 weeks). Cluster volumes were analyzed as a function of age using multivariate linear regression. Differences in cluster volumes between control subjects (n = 42, GW at MRI ranging from 39.0 to 48.7 weeks, mean {+/-} SD: 42.55 {+/-} 1.96 weeks) and newborns with congenital heart disease (CHD) (n = 49, GW at MRI ranging from 37.6 to 42.9 weeks, mean {+/-} SD: 40.23 {+/-} 1.30 weeks) were analyzed using variance analysis, controlling for sex and age at MRI scan. The clustering on average had a within-subject overlap of 0.811 (Dice overlap metric). While absolute thalamus volumes increased with age, their relative volumes remained stable in the studied developmental period. CHD infants shown reduced absolute volumes in six of the seven thalamic nuclei, with significant increasing in the relative volume of the cluster overlapping with the mediodorsal nucleus. While the perinatal period comprises rapid developmental events including the maturation of white matter, the topography of thalamic circuitry remains stable. Our study highlights alterations in thalamic topology and potential impacts on brain connectivity in CHD infants. By leveraging local diffusion properties from diffusion MRI, our validated segmentation technique offers a robust, data-centric approach to thalamic delineation.

neuroscience↗

bioRxiv2023

Characterization of dynamic patterns of human fetal to neonatal brain asymmetry with deformation-based morphometry

Despite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans. Super-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants age and sex and using threshold-free cluster enhancement. Fetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical grey matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints. While these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development.

neuroscience↗

bioRxiv2020

Mental development is associated with cortical connectivity of the ventral and nonspecific thalamus of preterm newborns

The thalamus is a key hub for regulating cortical connectivity. Dysmaturation of thalamocortical networks that accompany white matter injury have been hypothesized as neuroanatomical correlate of late life neurocognitive impairment following preterm birth. Our objective was to find a link between thalamocortical connectivity measures at term equivalent age and two year neurodevelopmental outcome in preterm infants. Diffusion tensor MRI of 58 infants (postmenstrual age at birth, mean (SD), 29.71 (1.47) weeks) was used to trace connections between the cortex and thalami. We found strong correlation between mental developmental index and two complementary measures of thalamocortical networks: connectivity strength projected to a cortical skeleton and pathway length emerging from thalamic voxels (partial correlation, R=0.552 and R=0.535, respectively, threshold-free cluster enhancement, corrected p-value<0.05), while psychomotor development was not associated with thalamocortical connectivity. Post hoc stepwise linear regression analysis revealed that parental socioeconomic scale, postmenstrual age and the duration of mechanical ventilation at the intensive care unit contribute to the variability of outcome. Our findings independently validated previous observations in preterm infants, providing additional evidence injury or dysmaturation of tracts emerging from ventral specific and various non-specific thalamus projecting to late-maturing cortical regions are predictive of mental, but not psychomotor developmental outcomes.

neuroscience↗

bioRxiv2019

Network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants

Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on the peripheral and feeder connections. EPO resulted in a globally increased clustering coefficient and higher local efficiency, while higher strength, efficiency and increased clustering was found for regions in the temporal lobe, supramarginal gyrus, inferior frontal gyrus, in the caudate and cingulate gyri. The connectivity network most affected by the EPO treatment showed a steeper increase in FA with age compared to the placebo group. These results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections.

neuroscience↗

bioRxiv2018

Left planum temporale growth predicts language development in newborns with congenital heart disease

Congenital heart diseases (CHD) are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits of higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. 44 newborns were included in our study, out of whom 33 were diagnosed with dextro-transposition of the great arteries (d-TGA) and 11 with other forms of severe CHD. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 {+/-} 7.03 days apart. MRI was performed in natural sleep on a 3.0T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation based morphometry, we calculated brain growth rate maps that reflected the rate of non-linear deformation that occurs between pre- and post-operative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the left planum temporale and the posterior operculum of the left frontal lobe and language score at 12 months of age, corrected for demographic variables (p=0.018, t=5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacts with this correlation with longer hospitalization stay results in faster enlargement of the internal cerebro-spinal fluid spaces. Our study provides evidence to the early importance of left-dominant perisylvian regions in language development even before the direct postnatatal exposure to native language. In CHD patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at one year of age.

neuroscience↗

bioRxiv2017

Intra-voxel incoherent motion magnetic resonance imaging of the living human fetus: the technique and within-subject reproducibility

Our purpose was to test the within-subject repeatability of the perfusion fraction, diffusion coefficient and pseudo diffusion coefficient measurements in various fetal organs and in the placenta based on the intra-voxel incoherent motion imaging principle. In utero diffusion-weighted magnetic resonance imaging was performed on 1.5T and 3.0T clinical scanners with b-factors ranging from 0 to 900 s/mm2 in 16 steps and a tetrahedral diffusion-weighting encoding scheme. Data from 16 pregnant women (maternal age: 34 {+/-} 4.9 years, range: 24.6 -40.8) were included in this pilot study. For 15 cases, IVIM was repeated (maternal age: 33.7 {+/-} 5.2 years, range: 24.6 - 40.8). A bi-exponential model was fitted on the volume-averaged diffusion values and the perfusion fraction (f), diffusion coefficient (d) and pseudo diffusion coefficient (D*) were calculated. Within-subject repeatability was given as the test-retest variability of the IVIM parameters in the fetal frontal cortex, frontal white matter, cerebellum, lungs, kidneys, liver and in the placenta. An in-house developed image processing script was utilized to remove the image frames with excessive motion, and to perform motion correction by using non-linear freeform deformations. For the fetal lungs, liver and the placenta, within-subject variability ranged from 14.4% to 20.4% for f, 12.2% to 14.1% for d and 16.8% to 25.3% for D*. The diffusion coefficients of the investigated brain regions were moderately to highly reproducible (4.8% to 15.2%), however, f and D* showed inferior reproducibility compared to corresponding measures derived for the lungs, liver and placenta. The IVIM-based parameters of the fetal kidney were revealed to be highly variable across scans. Our results indicate that in utero intra-voxel incoherent motion magnetic resonance imaging potentially provides a novel method for examining microvascular perfusion and diffusion in the developing human fetus. The reproducible quantification of the perfusion and diffusion parameters depend greatly upon data quality, fetal and maternal movements, and image post processing to detect and remove corrupted data before calculating the IVIM model.

bioinformatics↗

bioRxiv2017

In Utero Diffusion Tensor Imaging Of The Fetal Brain: A Reproducibility Study

Our purpose was to evaluate the within-subject reproducibility of in utero diffusion tensor imaging (DTI) metrics and the visibility of major white matter structures.\n\nImages for 30 fetuses (20-33. postmenstrual weeks, normal neurodevelopment: 6 cases, cerebral pathology: 24 cases) were acquired on 1.5T or 3.0T MRI. DTI with 15 diffusion-weighting directions was repeated three times for each case, TR/TE: 2200/63 ms, voxel size: 1*1 mm, slice thickness: 3-5 mm, b-factor: 700 s/mm2. Reproducibility was evaluated from structure detectability, variability of DTI measures using the coefficient of variation (CV), image correlation and structural similarity across repeated scans for six selected structures. The effect of age, scanner type, presence of pathology was determined using Wilcoxon rank sum test.\n\nWhite matter structures were detectable in the following percentage of fetuses in at least two of the three repeated scans: corpus callosum genu 76%, splenium 64%, internal capsule, posterior limb 60%, brainstem fibers 40% and temporooccipital association pathways 60%. The mean CV of DTI metrics ranged between 3% and 14.6% and we measured higher reproducibility in fetuses with normal brain development. Head motion was negatively correlated with reproducibility, this effect was partially ameliorated by motion-correction algorithm using image registration. Structures on 3.0 T had higher variability both with- and without motion correction.\n\nFetal DTI is reproducible for projection and commissural bundles during mid-gestation, however, in 16-30% of the cases, data were corrupted by artifacts, resulting in impaired detection of white matter structures. To achieve robust results for the quantitative analysis of diffusivity and anisotropy values, fetal-specific image processing is recommended and repeated DTI is needed to ensure the detectability of fiber pathways.\n\nAbbreviations

neuroscience↗