Anatomo-functional correspondence in the superior temporal sulcus

The superior temporal sulcus (STS) is an intriguing region both for its complex anatomy and for the multiple functions that it hosts. Unfortunately, most studies explored either the functional organization or the anatomy of the STS only. Here, we link these two aspects by investigating anatomo-functional correspondences between the voice-sensitive cortex (Temporal Voice Areas) and the STS depth. To do so, anatomical and functional scans of 116 subjects were processed such as to generate individual surface maps on which both depth and functional voice activity can be analyzed. Individual depth profiles of manually drawn STS and functional profiles from a voice localizer (voice > non-voice) maps were extracted and compared to assess anatomo-functional correspondences. Three major results were obtained: first, the STS exhibits a highly significant rightward depth asymmetry in its middle part. Second, there is an anatomo-functional correspondence between the location of the voice-sensitive peak and the deepest point inside this asymmetrical region bilaterally. Finally, we showed that this correspondence was independent of the gender and, using a machine learning approach, that it existed at the individual level. These findings offer new perspectives for the understanding of anatomo-functional correspondences in this complex cortical region

Application of machine learning to automated analysis of cerebral edema in large cohorts of ischemic stroke patients

Cerebral edema contributes to neurological deterioration and death after hemispheric stroke but there remains no effective means of preventing or accurately predicting its occurrence. Big data approaches may provide insights into the biologic variability and genetic contributions to severity and time course of cerebral edema. These methods require quantitative analyses of edema severity across large cohorts of stroke patients. We have proposed that changes in cerebrospinal fluid (CSF) volume over time may represent a sensitive and dynamic marker of edema progression that can be measured from routinely available CT scans. To facilitate and scale up such approaches we have created a machine learning algorithm capable of segmenting and measuring CSF volume from serial CT scans of stroke patients. We now present results of our preliminary processing pipeline that was able to efficiently extract CSF volumetrics from an initial cohort of 155 subjects enrolled in a prospective longitudinal stroke study. We demonstrate a high degree of reproducibility in total cranial volume registration between scans (R = 0.982) as well as a strong correlation of baseline CSF volume and patient age (as a surrogate of brain atrophy, R = 0.725). Reduction in CSF volume from baseline to final CT was correlated with infarct volume (R = 0.715) and degree of midline shift (quadratic model, p < 2.2 × 10−16). We utilized generalized estimating equations (GEE) to model CSF volumes over time (using linear and quadratic terms), adjusting for age. This model demonstrated that CSF volume decreases over time (p < 2.2 × 10−13) and is lower in those with cerebral edema (p = 0.0004). We are now fully automating this pipeline to allow rapid analysis of even larger cohorts of stroke patients from multiple sites using an XNAT (eXtensible Neuroimaging Archive Toolkit) platform. Data on kinetics of edema across thousands of patients will facilitate precision approaches to prediction of malignant edema as well as modeling of variability and further understanding of genetic variants that influence edema severity

Vertexwise sulcal width map computed over the human cortical surface using Magnetic Resonance Imaging

The human cortex is folded into a pattern of well-defined outward folds called gyri and buried inward folds known as sulci. The shape and size of the human cortex can be quantified and these quantifications can be used as biomarkers. Biomarkers may play an important role in the diagnosis and prognosis of neurological diseases. Two shape descriptors that have been largely ignored are the distance between the sulcal banks, i.e. the sulcal width, and the top-to-bottom distance of sulci, i.e. sulcal depth. In this work, a new method is proposed for quantitative assessment of sulcal width and depth from MRI T1-weighted images. The main steps during the image processing method include: (1) the extraction of sulcal lines and gyral crowns from the anatomy of the sulcus and (2) the normalization of the cortical surface such that pattern irregularities are taken into account, and (3) the generation of a vertex-wise sulcal width and depth maps. A validation of the proposed method is presented and, in addition, an example of a potential application of the method. We foresee that the developed method is applicable to research aimed at quantifying cortical shape for clinical as well as non-clinical purposes.Ingeniería Biomédic

Surface-Based tools for Characterizing the Human Brain Cortical Morphology

Tesis por compendio de publicacionesThe cortex of the human brain is highly convoluted. These characteristic convolutions present advantages over lissencephalic brains. For instance, gyrification allows an expansion of cortical surface area without significantly increasing the cranial volume, thus facilitating the pass of the head through the birth channel. Studying the human brain’s cortical morphology and the processes leading to the cortical folds has been critical for an increased understanding of the pathological processes driving psychiatric disorders such as schizophrenia, bipolar disorders, autism, or major depression. Furthermore, charting the normal developmental changes in cortical morphology during adolescence or aging can be of great importance for detecting deviances that may be precursors for pathology. However, the exact mechanisms that push cortical folding remain largely unknown. The accurate characterization of the neurodevelopment processes is challenging. Multiple mechanisms co-occur at a molecular or cellular level and can only be studied through the analysis of ex-vivo samples, usually of animal models. Magnetic Resonance Imaging can partially fill the breach, allowing the portrayal of the macroscopic processes surfacing on in-vivo samples. Different metrics have been defined to measure cortical structure to describe the brain’s morphological changes and infer the associated microstructural events. Metrics such as cortical thickness, surface area, or cortical volume help establish a relation between the measured voxels on a magnetic resonance image and the underlying biological processes. However, the existing methods present limitations or room for improvement. Methods extracting the lines representing the gyral and sulcal morphology tend to over- or underestimate the total length. These lines can provide important information about how sulcal and gyral regions function differently due to their distinctive ontogenesis. Nevertheless, some methods label every small fold on the cortical surface as a sulcal fundus, thus losing the perspective of lines that travel through the deeper zones of a sulcal basin. On the other hand, some methods are too restrictive, labeling sulcal fundi only for a bunch of primary folds. To overcome this issue, we have proposed a Laplacian-collapse-based algorithm that can delineate the lines traversing the top regions of the gyri and the fundi of the sulci avoiding anastomotic sulci. For this, the cortex, represented as a 3D surface, is segmented into gyral and sulcal surfaces attending to the curvature and depth at every point of the mesh. Each resulting surface is spatially filtered, smoothing the boundaries. Then, a Laplacian-collapse-based algorithm is applied to obtain a thinned representation of the morphology of each structure. These thin curves are processed to detect where the extremities or endpoints lie. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the structure topology and connectivity between the endpoints. The assessment of the presented algorithm showed that the labeled sulcal lines were close to the proposed ground truth length values while crossing through the deeper (and more curved) regions. The tool also obtained reproducibility scores better or similar to those of previous algorithms. A second limitation of the existing metrics concerns the measurement of sulcal width. This metric, understood as the physical distance between the points on opposite sulcal banks, can come in handy in detecting cortical flattening or complementing the information provided by cortical thickness, gyrification index, or such features. Nevertheless, existing methods only provided averaged measurements for different predefined sulcal regions, greatly restricting the possibilities of sulcal width and ignoring the intra-region variability. Regarding this, we developed a method that estimates the distance from each sulcal point in the cortex to its corresponding opposite, thus providing a per-vertex map of the physical sulcal distances. For this, the cortical surface is sampled at different depth levels, detecting the points where the sulcal banks change. The points corresponding to each sulcal wall are matched with the closest point on a different one. The distance between those points is the sulcal width. The algorithm was validated against a simulated sulcus that resembles a simple fold. Then the tool was used on a real dataset and compared against two widely-used sulcal width estimation methods, averaging the proposed algorithm’s values into the same region definition those reference tools use. The resulting values were similar for the proposed and the reference methods, thus demonstrating the algorithm’s accuracy. Finally, both algorithms were tested on a real aging population dataset to prove the methods’ potential in a use-case scenario. The main idea was to elucidate fine-grained morphological changes in the human cortex with aging by conducting three analyses: a comparison of the age-dependencies of cortical thickness in gyral and sulcal lines, an analysis of how the sulcal and gyral length changes with age, and a vertex-wise study of sulcal width and cortical thickness. These analyses showed a general flattening of the cortex with aging, with interesting findings such as a differential age-dependency of thickness thinning in the sulcal and gyral regions. By demonstrating that our method can detect this difference, our results can pave the way for future in vivo studies focusing on macro- and microscopic changes specific to gyri or sulci. Our method can generate new brain-based biomarkers specific to sulci and gyri, and these can be used on large samples to establish normative models to which patients can be compared. In parallel, the vertex-wise analyses show that sulcal width is very sensitive to changes during aging, independent of cortical thickness. This corroborates the concept of sulcal width as a metric that explains, in the least, the unique variance of morphology not fully captured by existing metrics. Our method allows for sulcal width vertex-wise analyses that were not possible previously, potentially changing our understanding of how changes in sulcal width shape cortical morphology. In conclusion, this thesis presents two new tools, open source and publicly available, for estimating cortical surface-based morphometrics. The methods have been validated and assessed against existing algorithms. They have also been tested on a real dataset, providing new, exciting insights into cortical morphology and showing their potential for defining innovative biomarkers.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Juan Domingo Gispert López.- Secretario: Norberto Malpica González de Vega.- Vocal: Gemma Cristina Monté Rubi

Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upennComment: Preprint submitted to NeuroImage Project website: https://pulkit-khandelwal.github.io/exvivo-brain-upen

A 3D explainability framework to uncover learning patterns and crucial sub-regions in variable sulci recognition

Precisely identifying sulcal features in brain MRI is made challenging by the variability of brain folding. This research introduces an innovative 3D explainability frame-work that validates outputs from deep learning networks in their ability to detect the paracingulate sulcus, an anatomical feature that may or may not be present on the frontal medial surface of the human brain. This study trained and tested two networks, amalgamating local explainability techniques GradCam and SHAP with a dimensionality reduction method. The explainability framework provided both localized and global explanations, along with accuracy of classification results, revealing pertinent sub-regions contributing to the decision process through a post-fusion transformation of explanatory and statistical features. Leveraging the TOP-OSLO dataset of MRI acquired from patients with schizophrenia, greater accuracies of paracingulate sulcus detection (presence or absence) were found in the left compared to right hemispheres with distinct, but extensive sub-regions contributing to each classification outcome. The study also inadvertently highlighted the critical role of an unbiased annotation protocol in maintaining network performance fairness. Our proposed method not only offers automated, impartial annotations of a variable sulcus but also provides insights into the broader anatomical variations associated with its presence throughout the brain. The adoption of this methodology holds promise for instigating further explorations and inquiries in the field of neuroscience

Learning and comparing functional connectomes across subjects

Functional connectomes capture brain interactions via synchronized fluctuations in the functional magnetic resonance imaging signal. If measured during rest, they map the intrinsic functional architecture of the brain. With task-driven experiments they represent integration mechanisms between specialized brain areas. Analyzing their variability across subjects and conditions can reveal markers of brain pathologies and mechanisms underlying cognition. Methods of estimating functional connectomes from the imaging signal have undergone rapid developments and the literature is full of diverse strategies for comparing them. This review aims to clarify links across functional-connectivity methods as well as to expose different steps to perform a group study of functional connectomes