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Christian Schiffer

Publications and source records attributed to Christian Schiffer.

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CytoNet: A Foundation Model for the Human Cerebral Cortex at Cellular Resolution

Studying the cellular architecture of the human cerebral cortex is essential for understanding how the brain is organized from the micro to the macro level, and how it functions. However, investigating complex texture patterns in histological images using automatic methods that can be scaled across whole brains remains a challenge. Here we introduce CytoNet, a foundation model trained on 1 million unlabeled microscopic image patches from over 4,000 histological sections from nine postmortem brains, and evaluated on over 2,000 sections from five additional brains excluded from self-supervised pretraining. Using co-localization in the cortical sheet for self-supervision, CytoNet learns to encode complex cellular patterns into expressive and anatomically meaningful feature representations. CytoNet supports multiple downstream applications, including area classification, laminar segmentation, quantification of microarchitectural variation, and exploratory mapping of cortical subdivisions. Functional parcellation analyses provided parcellation-dependent evidence for links between cytoarchitecture and macroscale functional organization. Together, these results establish CytoNet as a unified framework for scalable analysis of cortical microarchitecture and for testing links between cellular architecture and structure-function organization in the human cerebral cortex.

q-bio.NC

Cytoarchitecture in Words: Weakly Supervised Vision-Language Modeling for Human Brain Microscopy

Vision foundation models increasingly support interactive scientific workflows, but natural-language interaction requires coupling visual representations to language. Curated image-text pairs for this coupling are scarce in many biomedical domains. This is the case for cell-body-stained histological sections of the human brain, where microscopic image patches encode cytoarchitecture: cellular density, morphology, laminar structure, and areal organization. We propose retrieve-and-enrich supervision, a weakly supervised scheme for training image-conditioned language models without curated image-text pairs. The method retrieves label-level text from the literature via a shared anatomical label, then enriches it with image-specific properties such as cortical layer thickness and cell density. Labels provide training targets only, not model inputs. We use this scheme to couple CytoNet, a cytoarchitectonic vision foundation model, to an open-weight large language model via a lightweight Flamingo-style adapter. Across 57 brain areas, the resulting model produces plausible cytoarchitectonic descriptions, supports open-set use by rejecting out-of-scope areas, and predicts the correct area for in-scope patches with 90.6% accuracy. Removing explicit area names from generated text still leaves descriptions sufficient for a language model to recover the area in an 8-way test with 68.6% accuracy. A second instruction-tuned model trained with image-specific targets recovers cortical layer thickness and cell-densities from individual patches, allowing the model to read out information beyond canonical area descriptions. Our results show that retrieve-and-enrich supervision offers a practical route to vision-language training in specialized imaging domains where labels and expert text exist but image-level captions do not.

cs.CV

Dispersion-Guided Physics-Aware Deep Inverse Operator for Surface Wave Mode Separation

Surface-wave (SW) dispersion analysis is widely used in near-surface geophysics and seismology to determine shear-wave velocity structures by measuring SW geometric dispersion in seismic data. Among the available approaches, multichannel analysis of surface waves (MASW) and two-station methods are commonly employed to extract dispersion information for SW inversion. However, the coexistence of fundamental and higher modes in seismic data poses challenges for these methods, particularly for two-station analysis. To separate the different mode components, we propose a physics-aware unsupervised deep-learning framework. The method acts as a deep inverse operator that directly separates fundamental- and higher-mode components in the time-space domain using an adaptive Gaussian mask constructed in the frequency-phase-velocity (f-v) domain. Physical constraints are incorporated into the loss function by maximizing energy concentration within the target mask while suppressing leakage outside it. Through backpropagation, the network learns the inverse mapping from physical constraints in the f-v domain to wavefield separation in the time-space domain without requiring labeled training data. Numerical experiments on both synthetic and field data show that the framework provides a robust and automated solution for SW mode separation, facilitating more reliable dispersion-curve picking and improving the accuracy of subsequent SW inversion.

physics.geo-ph

Quantum Deep Learning: A Comprehensive Review

Quantum deep learning (QDL) explores the use of both quantum and quantum-inspired resources to determine when deep learning's core capabilities, such as expressivity, generalization, and scalability, can be enhanced based on specific resource constraints. Distinct from broader quantum machine learning, QDL emphasizes compositional depth at the pipeline level and the integration of quantum or quantum-inspired components within end-to-end workflows. This review provides an operational definition of QDL and introduces a taxonomy comprising four primary paradigms: hybrid quantum-classical models, quantum deep neural networks, quantum algorithms for deep learning primitives, and quantum-inspired classical algorithms. Theoretical principles are connected to advanced architectures, software toolchains, and experimental demonstrations across superconducting, trapped-ion, photonic, semiconductor spin, and neutral-atom systems, as well as quantum annealers. Claims of quantum advantage are critically assessed by distinguishing provable complexity-theoretic separations from empirical observations. The analysis characterizes trade-offs between model expressivity, trainability, and classical simulability, while systematically detailing the bottlenecks imposed by optimization landscapes, input-output access models, and hardware constraints. Applications are surveyed in domains encompassing image classification, natural language processing, scientific discovery, quantum data processing, and quantum optimal control, underscoring fair benchmarking against optimized classical counterparts and a comprehensive assessment of resource requirements. This review serves as a tutorial entry point for graduate students while guiding readers to specialized literature. It concludes with a verification-aware roadmap to transition QDL from near-term demonstrations to scalable and fault-tolerant implementations.

quant-ph

From Fibers to Cells: Fourier-Based Registration Enables Virtual Cresyl Violet Staining From 3D Polarized Light Imaging

Comprehensive assessment of the various aspects of the brain's microstructure requires the use of complementary imaging techniques. This includes measuring the spatial distribution of cell bodies (cytoarchitecture) and nerve fibers (myeloarchitecture). The gold standard for cytoarchitectonic analysis is light microscopic imaging of cell-body stained tissue sections. To reveal the 3D orientations of nerve fibers, 3D Polarized Light Imaging (3D-PLI) has been introduced, a method that is label-free and allows subsequent staining of sections after 3D-PLI measurement. By post-staining for cell bodies, a direct link between fiber- and cytoarchitecture can potentially be established in the same section. However, inevitable distortions introduced during the staining process make a costly nonlinear and cross-modal registration necessary in order to study the detailed relationships between cells and fibers in the images. In addition, the complexity of processing histological sections for post-staining only allows for a limited number of such samples. In this work, we take advantage of deep learning methods for image-to-image translation to generate a virtual staining of 3D-PLI that is spatially aligned at the cellular level. We use a supervised setting, building on a unique dataset of brain sections, to which Cresyl violet staining has been applied after 3D-PLI measurement. To ensure high correspondence between both modalities, we address the misalignment of training data using Fourier-based registration. In this way, registration can be efficiently calculated during training for local image patches of target and predicted staining. We demonstrate that the proposed method can predict a Cresyl violet staining from 3D-PLI, resulting in a virtual staining that exhibits plausible patterns of cell organization in gray matter, with larger cell bodies being localized at their expected positions.

eess.IV

Self-Supervised Representation Learning for Nerve Fiber Distribution Patterns in 3D-PLI

A comprehensive understanding of the organizational principles in the human brain requires, among other factors, well-quantifiable descriptors of nerve fiber architecture. Three-dimensional polarized light imaging (3D-PLI) is a microscopic imaging technique that enables insights into the fine-grained organization of myelinated nerve fibers with high resolution. Descriptors characterizing the fiber architecture observed in 3D-PLI would enable downstream analysis tasks such as multimodal correlation studies, clustering, and mapping. However, best practices for observer-independent characterization of fiber architecture in 3D-PLI are not yet available. To this end, we propose the application of a fully data-driven approach to characterize nerve fiber architecture in 3D-PLI images using self-supervised representation learning. We introduce a 3D-Context Contrastive Learning (CL-3D) objective that utilizes the spatial neighborhood of texture examples across histological brain sections of a 3D reconstructed volume to sample positive pairs for contrastive learning. We combine this sampling strategy with specifically designed image augmentations to gain robustness to typical variations in 3D-PLI parameter maps. The approach is demonstrated for the 3D reconstructed occipital lobe of a vervet monkey brain. We show that extracted features are highly sensitive to different configurations of nerve fibers, yet robust to variations between consecutive brain sections arising from histological processing. We demonstrate their practical applicability for retrieving clusters of homogeneous fiber architecture, performing classification with minimal annotations, and query-based retrieval of characteristic components of fiber architecture such as U-fibers.

cs.CV

Denoising Diffusion Probabilistic Models for Image Inpainting of Cell Distributions in the Human Brain

Recent advances in imaging and high-performance computing have made it possible to image the entire human brain at the cellular level. This is the basis to study the multi-scale architecture of the brain regarding its subdivision into brain areas and nuclei, cortical layers, columns, and cell clusters down to single cell morphology Methods for brain mapping and cell segmentation exploit such images to enable rapid and automated analysis of cytoarchitecture and cell distribution in complete series of histological sections. However, the presence of inevitable processing artifacts in the image data caused by missing sections, tears in the tissue, or staining variations remains the primary reason for gaps in the resulting image data. To this end we aim to provide a model that can fill in missing information in a reliable way, following the true cell distribution at different scales. Inspired by the recent success in image generation, we propose a denoising diffusion probabilistic model (DDPM), trained on light-microscopic scans of cell-body stained sections. We extend this model with the RePaint method to impute missing or replace corrupted image data. We show that our trained DDPM is able to generate highly realistic image information for this purpose, generating plausible cell statistics and cytoarchitectonic patterns. We validate its outputs using two established downstream task models trained on the same data.

eess.IV

2D histology meets 3D topology: Cytoarchitectonic brain mapping with Graph Neural Networks

Cytoarchitecture describes the spatial organization of neuronal cells in the brain, including their arrangement into layers and columns with respect to cell density, orientation, or presence of certain cell types. It allows to segregate the brain into cortical areas and subcortical nuclei, links structure with connectivity and function, and provides a microstructural reference for human brain atlases. Mapping boundaries between areas requires to scan histological sections at microscopic resolution. While recent high-throughput scanners allow to scan a complete human brain in the order of a year, it is practically impossible to delineate regions at the same pace using the established gold standard method. Researchers have recently addressed cytoarchitectonic mapping of cortical regions with deep neural networks, relying on image patches from individual 2D sections for classification. However, the 3D context, which is needed to disambiguate complex or obliquely cut brain regions, is not taken into account. In this work, we combine 2D histology with 3D topology by reformulating the mapping task as a node classification problem on an approximate 3D midsurface mesh through the isocortex. We extract deep features from cortical patches in 2D histological sections which are descriptive of cytoarchitecture, and assign them to the corresponding nodes on the 3D mesh to construct a large attributed graph. By solving the brain mapping problem on this graph using graph neural networks, we obtain significantly improved classification results. The proposed framework lends itself nicely to integration of additional neuroanatomical priors for mapping.

eess.IV

Contrastive Representation Learning for Whole Brain Cytoarchitectonic Mapping in Histological Human Brain Sections

Cytoarchitectonic maps provide microstructural reference parcellations of the brain, describing its organization in terms of the spatial arrangement of neuronal cell bodies as measured from histological tissue sections. Recent work provided the first automatic segmentations of cytoarchitectonic areas in the visual system using Convolutional Neural Networks. We aim to extend this approach to become applicable to a wider range of brain areas, envisioning a solution for mapping the complete human brain. Inspired by recent success in image classification, we propose a contrastive learning objective for encoding microscopic image patches into robust microstructural features, which are efficient for cytoarchitectonic area classification. We show that a model pre-trained using this learning task outperforms a model trained from scratch, as well as a model pre-trained on a recently proposed auxiliary task. We perform cluster analysis in the feature space to show that the learned representations form anatomically meaningful groups.

eess.IV

Convolutional Neural Networks for cytoarchitectonic brain mapping at large scale

Human brain atlases provide spatial reference systems for data characterizing brain organization at different levels, coming from different brains. Cytoarchitecture is a basic principle of the microstructural organization of the brain, as regional differences in the arrangement and composition of neuronal cells are indicators of changes in connectivity and function. Automated scanning procedures and observer-independent methods are prerequisites to reliably identify cytoarchitectonic areas, and to achieve reproducible models of brain segregation. Time becomes a key factor when moving from the analysis of single regions of interest towards high-throughput scanning of large series of whole-brain sections. Here we present a new workflow for mapping cytoarchitectonic areas in large series of cell-body stained histological sections of human postmortem brains. It is based on a Deep Convolutional Neural Network (CNN), which is trained on a pair of section images with annotations, with a large number of un-annotated sections in between. The model learns to create all missing annotations in between with high accuracy, and faster than our previous workflow based on observer-independent mapping. The new workflow does not require preceding 3D-reconstruction of sections, and is robust against histological artefacts. It processes large data sets with sizes in the order of multiple Terabytes efficiently. The workflow was integrated into a web interface, to allow access without expertise in deep learning and batch computing. Applying deep neural networks for cytoarchitectonic mapping opens new perspectives to enable high-resolution models of brain areas, introducing CNNs to identify borders of brain areas.

eess.IV