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Biology subjects

Schönlieb, C.-B.

Publications and source records attributed to Schönlieb, C.-B..

3 recordsLinked to original sources

Enhancing Brain Age Prediction and Neurodegeneration Detection with Contrastive Learning on Regional Biomechanical Properties

The aging process affects brain structure and function, yet its biomechanical properties remain underexplored. Magnetic Resonance Elastography (MRE) provides a unique perspective by mapping brain tissue stiffness and damping ratio, observables that correlate with age and disease. Using a self-supervised contrastive regression framework, we demonstrate that MRE surpasses conventional structural magnetic resonance imaging (MRI) in sensitivity. Specifically, stiffness captures Alzheimers disease (AD), while damping ratio detects subtle changes associated with mild cognitive impairment (MCI). Our regional analysis identifies deep brain structures, particularly the caudate and thalamus, as key biomarkers of aging. The greater age sensitivity of MRE translates to superior differentiation of AD and MCI from healthy individuals, pinpointing regions where significant biomechanical alterations occur, notably the thalamus in AD and hippocampus in MCI. Furthermore, our results reveal biomechanical alterations in cognitively healthy individuals whose aging profiles closely resemble patients with MCI and AD. These findings highlight MREs potential as a biomarker for early neurodegenerative changes, aiding dementia risk detection and early intervention.

neuroscience↗

Label-free prediction of Cell Painting from brightfield images

Cell Painting is a high-content image-based assay which can reveal rich cellular morphology and is applied in drug discovery to predict bioactivity, assess toxicity and understand diverse mechanisms of action of chemical and genetic perturbations. In this study, we investigate label-free Cell Painting by predicting the five fluorescent Cell Painting channels from paired brightfield z-stacks using deep learning models. We train and validate the models with a dataset representing 1000s of pan-assay interference compounds sampled from 17 unique batches. The model predictions are evaluated using a test set from two additional batches, treated with compounds comprised from a publicly available phenotypic set. In addition to pixel-level evaluation, we process the label-free Cell Painting images with a segmentation-based feature-extraction pipeline to understand whether the generated images are useful in downstream analysis. The mean Pearson correlation coefficient (PCC) of the images across all five channels is 0.84. Without actually incorporating these features into the model training we achieved a mean correlation of 0.45 from the features extracted from the images. Additionally we identified 30 features which correlated greater than 0.8 to the ground truth. Toxicity analysis on the label-free Cell Painting resulted a sensitivity of 62.5% and specificity of 99.3% on images from unseen batches. Additionally, we provide a breakdown of the feature profiles by channel and feature type to understand the potential and limitation of the approach in morphological profiling. Our findings demonstrate that label-free Cell Painting has potential above the improved visualization of cellular components, and it can be used for downstream analysis. The findings also suggest that label-free Cell Painting could allow for repurposing the imaging channels for other non-generic fluorescent stains of more targeted biological interest, thus increasing the information content of the assay.

bioinformatics↗

Structural connectome quantifies tumor invasion and predicts survival in glioblastoma patients

Glioblastoma widely affects brain structure and function, and remodels neural connectivity. Characterizing the neural connectivity in glioblastoma may provide a tool to understand tumor invasion. Here, using a structural connectome approach based on diffusion MRI, we quantify the global and regional connectome disruptions in individual glioblastoma patients and investigate the prognostic value of connectome disruptions and topological properties. We show that the disruptions in the normal-appearing brain beyond the lesion could mediate the topological alteration of the connectome (P <0.001), associated with worse patient performance (P <0.001), cognitive function (P <0.001), and survival (overall survival: HR: 1.46, P = 0.049; progression-free survival: HR: 1.49, P = 0.019). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of remodeling, where increased connectivity is associated with better overall survival (log-rank P = 0.005). Our approach reveals the glioblastoma invasion invisible on conventional MRI, promising to benefit patient stratification and precise treatment.

neuroscience↗