CytoCLIP: Learning Cytoarchitectural Characteristics in Developing Human Brain Using Contrastive Language Image Pre-Training
Authors: Pralaypati Ta, Sriram Venkatesaperumal, Keerthi Ram, Mohanasankar Sivaprakasam
Organizations: Sudha Gopalakrishnan Brain Centre, Indian Institute of Technology, Madras, Chennai, India. · Department of Electrical Engineering, Indian Institute of Technology, Madras, Chennai, India.
Abstract
The functions of different regions of the human brain are closely linked to their distinct cytoarchitecture, which is defined by the spatial arrangement and morphology of the cells. Identifying brain regions by their cytoarchitecture enables various scientific analyses of the brain. However, delineating these areas manually in brain histological sections is time-consuming and requires specialized knowledge. An automated approach is necessary to minimize the effort needed from human experts. To address this, we propose CytoCLIP, a suite of vision-language models derived from pre-trained Contrastive Language-Image Pre-Training (CLIP) frameworks to learn joint visual-text representations of brain cytoarchitecture. CytoCLIP comprises two model variants: one is trained using low-resolution whole-region images to understand the overall cytoarchitectural pattern of an area, and the other is trained on high-resolution image tiles for detailed cellular-level representation. The training dataset is created from NISSL-stained histological sections of developing fetal brains of different gestational weeks. It includes 86 distinct regions for low-resolution images and 379 brain regions for high-resolution tiles. We evaluate the model's understanding of the cytoarchitecture and generalization ability using region classification and cross-modal retrieval tasks. Multiple experiments are performed under various data setups, including data from samples of different ages and sectioning planes. Experimental results demonstrate that CytoCLIP outperforms existing methods. It achieves a weighted F1 score of 0.87 for whole-region classification and 0.91 for high-resolution image tile classification.
Understanding the relationship between deep visual representations and the human visual system is a fundamental challenge in computational neuroscience. While modern vision models achieve strong performance in image recognition, their correspondence with the hierarchical organization of the human visual cortex remains an open question. In this study, we propose CHASMBrain, a novel hierarchical two-stage framework for image-to-fMRI encoding. Our architecture leverages a dual-stream Mamba design to explicitly separate and process global semantic tokens and local spatial patches, motivated by the functional organization of the visual cortex. A coarse-to-fine strategy is employed: Stage 1 predicts denoised ROI-level activations, while Stage 2 refines these coarse responses into full voxel-level predictions using a Mamba-VAE. Experiments on the Natural Scenes Dataset (NSD) demonstrate that our method achieves a Pearson correlation of 0.429 and an MSE of 0.261, outperforming all evaluated baselines including ridge regression and DINOv2 linear probes. Beyond predictive performance, causal branch-ablation experiments reveal an asymmetric specialization: the patch stream is specifically locked to early visual cortex (retinotopic regions), while the CLS stream contributes broader semantic context to higher-order areas -- a correspondence that holds causally, not merely correlationally. Cross-subject transfer experiments further show that the learned backbone generalizes across individuals with minimal per-subject adaptation, suggesting the model captures a shared, subject-agnostic visual representation.
Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.
Contrastive Language-Image Pre-training (CLIP) has been shown to have limitations in its fine-grained dense feature representation, due to its pre-training focusing on matching the whole image to a text description. Considering the large data and computational burden in pre-training a vision-language model from scratch, a series of works aim to enhance the fine-grained ability of CLIP through a fine-tuning scheme. However, existing works suffer from a variety of limitations: additional region annotations are usually required, which limits the semantic diversity due to the predefined categories and leads to a large effort to process the training data; and they usually sacrifice CLIP's original ability for global visual representation. To bypass these limitations, we propose SFF-CLIP (Self-annotated Fine-grained Fine-tuning for CLIP), which only uses image-text pairs as input to boost the fine-grained representation ability in the CLIP fine-tuning, while maintaining the global visual-semantic consistency. Concretely, a run-time region-phrase alignment scheme is designed, which obtains concept phrases from the input sentence, and aligns them with corresponding extracted region-based features using text-specific heat maps. Extensive experiments demonstrate that SFF-CLIP leads to significant performance improvements on fine-grained dense feature representation, as well as maintaining the performance of the original CLIP on image-level tasks. Code will be released later.