Biology subjects

Bach Cuadra, M.

Publications and source records attributed to Bach Cuadra, M..

12 recordsLinked to original sources

bioRxiv2026

Characterization of Fetal Cortical Development Using Spectral Analysis of Gyrification (SPANGY)

The prenatal period of human brain development is critical for mental health and cognition across the entire lifespan. During this period, the cortex undergoes a dramatic transformation from a smooth lissencephalic surface into an elaborately folded structure, a process whose precise characterization is essential for understanding neurodevelopmental trajectories. This study represents the first application of Spectral Analysis of Gyrification (SPANGY) to a large multi-centric fetal brain MRI dataset (635 subjects, 20-38 weeks gestational age). SPANGY characterizes geometric variations on a surface based on the wavelength of folds, hence, providing a quantitative local description of gyrification at the individual level. Using rigorous normative modeling (GAMLSS) and statistical harmonization (ComBat-GAM), we established age-specific reference trajectories for multi-scale gyrification features (spectral frequency bands). We provide the first ever quantification of the temporally-ordered emergence of cortical folding in successive waves: the earliest-emerging low frequency, deep fissures are progressively superseded by the accelerating expansion of higher frequency folds. The normative curves provide the first step in taking prenatal neurodevelopmental assessment from qualitative inspection into a rigorous statistical inference, creating an objective reference against which deviations from healthy brain growth can be caught earlier, and with greater precision.

neuroscience↗

bioRxiv2026

Data quality biases normative models derived from fetal brain MRI

Normative modeling is increasingly used to characterize typical growth trajectories and identify atypical neurodevelopment, including early brain development using magnetic resonance imaging (MRI) acquired before birth. Recent work has emphasized the importance of large sample sizes for accurate and robust centile estimation. In this study, we investigate how image quality influences fetal brain normative models, a critical factor in this context where MRI is acquired on a moving fetus in utero. Using a multi-centric cohort of 635 fetal MRI scans, we applied a standardized visual quality control (QC) protocol with continuous quality ratings. We fit normative models for multiple brain structures under progressively relaxed QC stringency, and quantified the deviations in centile estimates relative to a high-quality reference subgroup. Our results showed that including lower-quality data systematically biased normative centiles, with the strongest effects observed in the outer centiles, particularly the lower tail (1st-10th). Bias increased progressively as QC stringency was relaxed and could not be attributed solely to the number of subjects used to fit the models. Quality-induced bias was structure-dependent, and often not visually apparent at the segmentation level. These findings highlight that image quality is an important source of bias in normative fetal brain modeling, and that increasing sample size at the expense of quality may systematically affect centile estimates, potentially jeopardizing the utility of the model.

neuroscience↗

bioRxiv2025

High-resolution whole-brain magnetic resonance spectroscopic imaging in youth at risk for psychosis

Advances in three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) allow for the high-resolution mapping of multiple neurometabolites throughout the entire brain in vivo and within clinically compatible time frames. Leveraging this capability, we created a voxel-based pipeline that corrects and spatially normalizes whole-brain maps of total N-acetylaspartate (tNAA), myo-inositol (Ins), choline compounds, glutamate + glutamine, and creatine + phosphocreatine. We examined 2 different 3D-MRSI dataset: first, a clinical sample of adolescents and young adults at risk for psychosis (n= 21) meeting DSM-5 criteria for Attenuated Psychosis Syndrome (APS) or Schizotypal Personality Disorder (SCZT), and age-/sex-matched healthy controls (n =13); and second, a non-clinical sample of adolescents (n = 61) scanned on a different site. The objective of the study was threefold: first, to assess the reproducibility of 3D-MRSI measures across datasets and scanning sites; second, to validate the feasibility of whole-brain, voxel-based analyses on 3D-MRSI data; and third, to test the sensitivity of this approach. Metabolite distributions showed reproducible regional variation in standard space between the two independent samples and scanning sites (r ranging from 0.82 to 0.99). Relative to controls, at-risk participants exhibited higher tNAA levels in frontal grey matter; the SCZT subgroup additionally displayed widespread cortical and subcortical elevations of Ins levels compared with both APS and controls. Voxel-based analyses of structural (i.e., gray and white matter volumes or densities) and diffusion (i.e., generalized fractional anisotropy) parameters yielded no significant differences between patients and controls. These preliminary findings suggest that high-resolution 3D-MRSI may be sensitive enough to detect subtle neurometabolic alterations at the group level in the early stages of psychotic disorders when structural or diffusion measures show no difference. High-resolution whole-brain metabolic mapping may have the potential to help with early identification of young people at risk for psychosis or other mental disorders.

neuroscience↗

bioRxiv2025

A-eye: Automated 3D Segmentation of Healthy Human Eyeand Orbit Structures and Axial Length Extraction

This study addresses the need for accurate 3D segmentation of the human eye and orbit from MRI to improve ophthalmic diagnostics. Past efforts focused on small sample sizes and varied imaging methods. Here, two techniques (atlas-based registration and supervised deep learning) are tested for automated segmentation on a large T1-weighted MRI dataset. Results show accurate segmentations of the lens, globe, optic nerve, rectus muscles, and fat. Additionally, the study automates the estimation of axial length, a key biomarker.

bioengineering↗

bioRxiv2025

Domain shifts in infant brain diffusion MRI: Quantification and mitigation for fODF estimation

The accurate estimation of fiber orientation distributions (fODFs) in diffusion magnetic resonance imaging (MRI) is crucial for understanding early brain development and its potential disruptions. While deep learning (DL) models have shown promise in fODF estimation from neonatal diffusion MRI (dMRI) data, the out-of-domain (OOD) performance of these models remains largely unexplored, especially under diverse domain shift scenarios. This study evaluated the robustness of three state-of-the-art DL architectures--MLP-based, Transformer-based, and U-Net/CNN-based--on fODF predictions derived from diffusion MRI data. Using 488 subjects from the developing Human Connectome Project (dHCP) and the Baby Connectome Project (BCP) datasets, we reconstructed reference fODFs from the full dMRI series using single-shell three-tissue constrained spherical deconvolution (SS3T-CSD) and multi-shell multi-tissue CSD (MSMT-CSD) to generate reference fODF reconstructions for model training, and systematically assessed the impact of age, scanner/protocol differences, and input dimensionality on model performance. Our findings reveal that U-Net consistently outperformed other models when fewer diffusion gradient directions were used, particularly with the SS3T-CSD-derived ground truth, which showed superior performance in capturing crossing fibers. However, as the number of input diffusion gradient directions increased, MLP and the transformer-based model exhibited steady gains in accuracy. Nevertheless, performance nearly plateaued from 28 to 45 input directions in all models. Age-related domain shifts were found to be less pronounced in late developmental stages (late neonates, and babies), with SS3T-CSD demonstrating greater robustness to variability compared to MSMT-CSD. To address inter-site domain shifts, we implemented two adaptation strategies: the Method of Moments (MoM) and fine-tuning. Fine-tuning consistently yielded superior results, with U-Net benefiting the most from increased target subjects. This study represents the first systematic evaluation of OOD settings in deep learning applications to fODF estimation, providing critical insights into model robustness and adaptation strategies for diverse clinical and research applications.

bioinformatics↗

bioRxiv2025

Functional organization of the neonatal thalamus across development depicted by functional MRI

The thalamus is a central component of the brain that is involved in a variety of functions, from sensory processing to high-order cognition. Its structure and function in the first weeks of extrauterine life, including its connections to different cortical and subcortical areas, have not yet been widely explored. Here, we used resting state functional magnetic resonance imaging data of 730 newborns from the developing Human Connectome Project to study the functional organization of the thalamus from 37 to 44 post-conceptual weeks. We introduce KNIT: K-means for Nuclei in Infant Thalamus. The framework employs a highly granular vector space of 40 features, each corresponding to functional connectivity to a brain region, using k-means clustering and uncertainty quantification through bootstrapping to delineate thalamic units. Although the different clusters showed common patterns of increased connectivity to the superior temporal gyrus, the parietal, and the frontal cortex, implying an expected decrease in specialization at that age, they also show some specificity. That is, a pulvinar unit was identified, similar to the adult thalamus. Ventrolateral motor and medial salience units were also highlighted. The latter appeared around 41 weeks of age, while the former showed at least from 37 weeks, but had a decrease in volume through age, replaced mostly by a dominant dorsal thalamic unit. We also observed an increase in clustering robustness and in hemispheric bilateral symmetry with age, suggesting more specialized functional units. We also found a burst in global thalamic connectivity around 41 weeks. Finally, we demonstrate the benefits of this method in terms of granularity compared to the more conventional winner-takes-all approach.

neuroscience↗

bioRxiv2024

Towards Longitudinal Characterization of Multiple Sclerosis Atrophy Employing SynthSeg Framework and Normative Modeling

Multiple Sclerosis (MS) is a complex neurodegenerative disease characterized by heterogeneous progression patterns. Traditional clinical measures like the Expanded Disability Status Scale (EDSS) inadequately capture the full spectrum of disease progression, highlighting the need for advanced Disease Progression Modeling (DPM) approaches. This study harnesses cutting-edge neuroimaging and deep learning techniques to investigate deviations in subcortical volumes in MS patients. We analyze T1-weighted and Fluid-attenuated inversion recovery (FLAIR) Magnetic Resonance Imaging (MRI) data using advanced DL segmentation models, SynthSeg+ and SynthSeg-WMH, which address the challenges of conventional methods in the presence of white matter lesions. By comparing subcortical volumes of 326 MS patients to a normative model from 37,407 healthy individuals, we identify significant deviations that enhance our understanding of MS progression. This study highlights the potential of integrating DL with normative modeling to refine MS progression characterization, automate informative MRI contrasts, and contribute to data-driven DPM in neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Exploiting XAI maps to improve MS lesion segmentation and detection in MRI

To date, several methods have been developed to explain deep learning algorithms for classification tasks. Recently, an adaptation of two of such methods has been proposed to generate instance-level explainable maps in a semantic segmentation scenario, such as multiple sclerosis (MS) lesion segmentation. In the mentioned work, a 3D U-Net was trained and tested for MS lesion segmentation, yielding an F1 score of 0.7006, and a positive predictive value (PPV) of 0.6265. The distribution of values in explainable maps exposed some differences between maps of true and false positive (TP/FP) examples. Inspired by those results, we explore in this paper the use of characteristics of lesion-specific saliency maps to refine segmentation and detection scores. We generate around 21000 maps from as many TP/FP lesions in a batch of 72 patients (training set) and 4868 from the 37 patients in the test set. 93 radiomic features extracted from the first set of maps were used to train a logistic regression model and classify TP versus FP. On the test set, F1 score and PPV were improved by a large margin when compared to the initial model, reaching 0.7450 and 0.7817, with 95% confidence intervals of [0.7358, 0.7547] and [0.7679, 0.7962], respectively. These results suggest that saliency maps can be used to refine prediction scores, boosting a models performances.

bioengineering↗

bioRxiv2024

Eye-Opening Advances: Automated 3D Segmentation, Key Biomarkers Extraction, and the First Large-Scale MRI Eye Atlas.

In this study we introduce an automated 3D segmentation of the healthy human adult eye and orbit from Magnetic Resonance Images, to improve ophthalmic diagnostics and treatments. Past efforts primarily focused on small sample sizes and varied imaging modalities. Here, we leverage a large-scale dataset of T1-weighted MRI of 1245 subjects and the use of the deep learning-based nnU-Net for MR-Eye segmentation tasks. The results showcase robust and accurate 3D segmentations of lens, globe, optic nerve, rectus muscles, and orbital fat. We also present the automated estimation of key ophthalmic morphometry biomarkers such as axial length and volumetry, while benchmarking correlations between body mass index and eye structure volumes. Quality control protocols are introduced through the pipeline to ensure the reliability of the segmented large-scale data, further enhancing the applicability of our algorithm in clinical research. As major outcome we provide the first large-scale unbiased eye atlases (female, male and combined) towards standardization of spatial normalization tools for MR-Eye.

bioengineering↗

bioRxiv2024

Assessing data quality on fetal brain MRI reconstruction: a multi-site and multi-rater study

Quality assessment (QA) has long been considered essential to guarantee the reliability of neuroimaging studies. It is particularly important for fetal brain MRI, where unpredictable fetal motion can lead to substantial artifacts in the acquired images. Multiple images are then combined into a single volume through super-resolution reconstruction (SRR) pipelines, a step that can also introduce additional artifacts. While multiple studies designed automated quality control pipelines, no work evaluated the reproducibility of the manual quality ratings used to train these pipelines. In this work, our objective is twofold. First, we assess the inter- and intra-rater variability of the quality scoring performed by three experts on over 100 SRR images reconstructed using three different SRR pipelines. The raters were asked to assess the quality of images following 8 specific criteria like blurring or tissue contrast, providing a multi-dimensional view on image quality. We show that, using a protocol and training sessions, artifacts like bias field and blur level still have a low agreement (ICC below 0.5), while global quality scores show very high agreement (ICC = 0.9) across raters. We also observe that the SRR methods are influenced differently by factors like gestational age, input data quality and number of stacks used by reconstruction. Finally, our quality scores allow us to unveil systematic weaknesses of the different pipelines, indicating how further development could lead to more robust, well rounded SRR methods. Our rating protocol is made available at https://doi.org/10.5281/zenodo.15696638.

neuroscience↗

bioRxiv2023

Deep learning microstructure estimation of developing brains from diffusion MRI: a newborn and fetal study

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to assess the brain white matter. Fiber orientation distribution functions (FODs) are a common way of representing the orientation and density of white matter fibers. However, with standard FOD computation methods, accurate estimation of FODs requires a large number of measurements that usually cannot be acquired for newborns and fetuses. We propose to overcome this limitation by using a deep learning method to map as few as six diffusion-weighted measurements to the target FOD. To train the model, we use the FODs computed using multi-shell high angular resolution measurements as target. Extensive quantitative evaluations show that the new deep learning method, using significantly fewer measurements, achieves comparable or superior results to standard methods such as Constrained Spherical Deconvolution. We demonstrate the generalizability of the new deep learning method across scanners, acquisition protocols, and anatomy on two clinical datasets of newborns and fetuses. Additionally, we compute agreement metrics within the HARDI newborn dataset, and validate fetal FODs with post-mortem histological data. The results of this study show the advantage of deep learning in inferring the microstructure of the developing brain from in-vivo dMRI measurements that are often very limited due to subject motion and limited acquisition times, but also highlight the intrinsic limitations of dMRI in the analysis of the developing brain microstructure. These findings, therefore, advocate for the need for improved methods that are tailored to studying the early development of human brain.

bioinformatics↗

bioRxiv2018

Higher order spherical harmonics reconstruction of fetal diffusion MRI with intensity correction

We present a comprehensive method for reconstruction of fetal diffusion MRI signal using a higher order spherical harmonics representation, that includes motion, distortion and intensity correction. By applying constrained spherical deconvolution and whole brain tractography to reconstructed fetal diffusion MRI we are able to identify main WM tracts and anatomically plausible fiber crossings. The proposed methodology facilitates detailed investigation of developing brain connectivity and microstructure in-utero.

neuroscience↗