Biology subjects

Bhatt, R. R.

Publications and source records attributed to Bhatt, R. R..

4 recordsLinked to original sources

bioRxiv2026

Regional choroid plexus calcifications and their associations with aging, brain structure, and disease

The choroid plexus (CP) maintains brain homeostasis through cerebrospinal fluid production and formation of the blood-cerebrospinal fluid barrier, and its dysfunction has been linked with aging and neurological disease. CP dysfunction may involve both enlargement and calcific tissue change, which may reflect distinct processes; yet population neuroimaging has focused on lateral ventricle CP volume, which cannot directly identify calcified tissue. Using quantitative susceptibility mapping (QSM) in 30,012 UK Biobank participants, we conducted, to our knowledge, the first large scale multi-ventricular study of CP calcification (CPcal), quantifying the lateral (LV), third (3rdV) and fourth (4thV) ventricles. We examined associations with age and sex, endocrine, nutritional and metabolic, mental and behavioral, nervous system, and circulatory diagnoses; family history of Alzheimer's disease and related dementias (ADRD); cardiometabolic traits; and brain macrostructure, white matter microstructure, and subcortical susceptibility. CPcal increased with age (largest association: LV, r = 0.191) and was greater in males in the LV and 3rdV (d = 0.249-0.359) and more prevalent in the 4thV (OR = 1.274). Greater CPcal was associated with endocrine and metabolic, psychiatric, nervous system, and circulatory disorders, with the strongest and most consistent associations observed in the 3rdV (d = 0.097 - 0.125) and persisted after adjustment for ventricular volume, particularly for diabetes (d = 0.303) and tobacco use disorder (d = 0.314). Maternal ADRD family history was associated with greater LV CPcal (d = 0.063). CPcal was also associated with cortical and subcortical volumes (r = 0.033 - 0.046), white matter microstructure (r = 0.017 - 0.042), and subcortical susceptibility (r = -0.064 - 0.131). QSM-derived CPcal is a scalable, radiation-free imaging phenotype that complements volumetry by characterizing calcific CP tissue, which is associated with cardiometabolic health, brain aging, and neurodegenerative risk, particularly in the third ventricle.

neuroscience↗

bioRxiv2026

FastEBM: Fast, Scalable, and Uncertainty-Aware Event-Based Disease Progression Modeling

Event-based models (EBMs) are used to infer ordering of biomarker alteration patterns with respect to disease progression. However, EBM approaches rely on computationally expensive permutation-based inference, assumptions of feature independence, and likelihood optimization that can limit scalability and stability in high-dimensional settings. Here, we introduce Fast Event-Based Model (FastEBM), a scalable, uncertainty aware, Markov- chain-based framework that reformulates disease progression inference as a subject-ordering problem on a data-driven diffusion manifold. The progression uncertainty, used to derive positional variance diagrams, is quantified using first-passage-time variability derived directly from the inferred Markov process. Using synthetic experiments varying feature dimensionality, cohort size, noise level, and feature-correlation structure, we compared FastEBM with established methods, including Gaussian mixture model EBM (GMM-EBM), kernel density estimation EBM (KDE-EBM), and discriminative EBM (DEBM). FastEBM achieved the best accuracy and runtime. In low-subject/high-dimensional stress tests, FastEBM retained event-order recovery. FastEBM remained robust in simulations containing correlated and redundant features after decorrelation and feature-group handling. We applied FastEBM to real-world data to characterize biomarker progression in Alzheimers disease. First, we evaluated a low-dimensional multi- modal dataset from The Alzheimers Disease Prediction Of Longitudinal Evolution (TAD- POLE) challenge. Second, to demonstrate high-dimensional disease progression mapping, we applied FastEBM to regional cortical tau-PET data from the Alzheimers Disease Neuroimaging Initiative (ADNI). In both cases, FastEBM recovered progression patterns broadly consistent with the literature, also revealing lateralized progression trends. These results show that diffusion-based Markov geometry provides a scalable and robust alternative to conventional event-based modeling. FastEBM is available at: https://github.com/sjusc07/FastEBM.

bioinformatics↗

bioRxiv2025

Assessing molecular, cellular and transcriptomic bases of laminar perfusion and cytoarchitecture coupling in the human cortex

Understanding how cellular architecture organizes cortical function requires mesoscopic approaches that resolve structure-function coupling in vivo. Here we introduce cerebral blood flow (CBF) and cell-body staining intensity (CSI) similarity index (CCSI), a localized similarity index between the CBF estimates from ultra-high-field 7T arterial spin labeling images and CSI from the BigBrain histology images to serve as a quantitative marker of laminar perfusion-cytoarchitecture coupling. CCSI revealed a reproducible, region- specific alignment between laminar vascular and cellular profiles across the cortex. Going beyond CBF, CCSI selectively tracked mitochondrial respiratory capacity and colocalized with capillary endothelial and mature non-myelination oligodendrocyte populations forming neurovascular interfaces. Transcriptomic enrichment highlighted pathways related to vascular remodeling, oxidative metabolism, and lipid-myelin homeostasis, indicating that CCSI reflects integrated metabolic-structural specialization. At the systems level, CCSI strengthened structure-function gradient correspondence in transmodal cortices, such as the default mode network. Together, these findings establish CCSI as a physiologically grounded, non-invasive marker of perfusion-cytoarchitecture alignment, providing a cross-scale framework linking cortical microstructure, metabolism, and functional organization.

neuroscience↗

bioRxiv2022

Multisite Test-Retest Reliability and Compatibility of Brain Metrics derived from FreeSurfer Versions 7.1, 6.0, and 5.3

Automatic neuroimaging segmentation and parcellation tools provide convenient and systematic methods for extracting numerous features from brain MRI scans, and are becoming standard practice for large-scale coordinated studies. One such tool, FreeSurfer, provides an easy-to-use pipeline to extract metrics describing cortical and subcortical morphometry. Over the past two decades, there have been over 25 stable releases of FreeSurfer, and different versions are used across published works. Despite this, the reliability and compatibility of metrics derived from the most recent major version releases have yet to be assessed empirically. Here, we use test-retest data from three public brain MRI datasets to assess within-version reliability and between-version compatibility across 42 regional outputs from three versions of FreeSurfer: the latest, v7.1, and two previous stable releases - v5.3, and v6.0. We find v7.1 was less compatible with older versions for measuring cortical thickness. In particular, the thickness of the cingulate gyrus had low compatibility (intraclass correlation coefficient (ICC) between 0.37 and 0.61) between versions. Temporal and frontal poles, and the medial orbitofrontal surface area metrics, also showed low to moderate compatibility with v7.1. While our work compares all three versions, our sub-comparisons between the older versions (v5.3 and v6.0) replicates earlier findings of low compatibility of pallidum and putamen volumes. Low between-version compatibility was not always indicative of low within-version reliability - all versions showed good to excellent reliability across most regional measures (ICC>0.8). Age associations, quality control metrics, and Dice coefficients in an independent sample of 106 individual scans, processed with all three versions of FreeSurfer, revealed differences in results of downstream statistical analysis. As neuroimaging studies adopt more recently released software, we provide researchers with a reference to highlight the regions and metrics that may yield findings inconsistent with published works using older FreeSurfer software. An interactive viewer for the results is provided at http://data.brainescience.org/Freesurfer_Reliability/

neuroscience↗