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CALHippo Framework - Codebase of the Cellular Annotation Library for the Hippocampus

Python uv PyTorch TensorFlow Dataset Models

Important

CALHippo has been accepted at MICCAI 2026! The current preprint version is available here. See the citation below.

Paper Dataset

The released dataset includes preprocessed HR crops, classified cell annotations, and a mesoscale point cloud. Use it to skip HR data preprocessing, segmentation, and classification; see Data setup.

This repository contains the official framework associated with the CALHippo dataset. It provides a multiscale workflow that bridges microscopic cell instances and macroscopic brain architecture, enabling the generation of biologically plausible 3D cellular point clouds from BigBrain histological sections.

CALHippo Logo

Pipeline

The framework preprocesses raw high-resolution (HR) (a) and low-resolution (LR) (e) BigBrain slices, segments and classifies HR cells (b), maps the annotations into LR space (c), trains LR density models (d), runs full-slice LR inference (f), and reconstructs 3D point-cloud outputs (g).

calhippo_pipeline

Results

HR Segmentation and Classification Merging Pipeline LR density predictions and sampled points
HR Segmentation, Merging and Classification (b) LR Full-Slice Density Prediction and Sampling (f)
CA mesoscale cell-resolved point cloud infographic
All CA Class Resolved Point Cloud Reconstruction (g)
Right Hippocampus Rotating Point Cloud All Classes
All CA Mesocale Volumes (left) and predicted point cloud (right)

Setup

Clone this repo, cd into the repository root and install uv:

curl -LsSf https://astral.sh/uv/install.sh | sh
#or if you don't have curl installed:
wget -qO- https://astral.sh/uv/install.sh | sh

Then install the dependencies:

uv sync

Optionally activate the environment:

source .venv/bin/activate

or run .py files directly using uv run instead of python.

Pipeline Usage

The released CALHippo dataset is available at https://ditto.ing.unimore.it/calhippo/. It includes 24 high-resolution BigBrain slices with CA1-CA4 cell annotations and a mesoscale point cloud. If you download it, you can skip HR preprocessing, HR segmentation, and HR classification. The dataset also includes the final released point cloud.

uv run python scripts/setup_data.py --data-root data --calhippo-dataset-zip CALHippo_Dataset_v1.0.zip

Choose a setup path:

Goal Start here
Use the released dataset and skip the HR pipeline Use The Released CALHippo Dataset
Reproduce the full process from raw data Download All Raw Data, then Pipeline Instructions

Reference documents:

Document Use it for
Data setup Data sources, setup script, folder structure, transform notes
Pipeline instructions Reproducibility path and inference-stage commands after data setup
HR/LR coordinate conventions Coordinate and affine rules for HR to LR mapping
HR/LR mapping notebook Visual/debug reference for HR/LR mapping

Data Layout

The maintained documentation uses a single configurable <DATA_ROOT> convention. The canonical tree is specified in Data setup.

Key folders:

  • raw inputs live under <DATA_ROOT>/raw/high_res, <DATA_ROOT>/raw/low_res, and <DATA_ROOT>/raw/masks
  • preprocessing outputs live under <DATA_ROOT>/input/all_regions and <DATA_ROOT>/input/single_regions
  • optional manually adjusted HR ROI masks can live under <DATA_ROOT>/input/custom_masks/high_res and be used explicitly during HR single-region extraction
  • pipeline outputs live under <DATA_ROOT>/output/segmentation, <DATA_ROOT>/output/classification, <DATA_ROOT>/output/lr_density_dataset, <DATA_ROOT>/output/test_lr_density_gt, <DATA_ROOT>/output/lr_gt_eval, <DATA_ROOT>/output/full_lr_predictions, and <DATA_ROOT>/output/mesoscale_reconstruction
  • density-estimator training runs live under <DATA_ROOT>/density_estimator_training
  • released and trained model artifacts live under <DATA_ROOT>/models

The maintained LR inference output is <DATA_ROOT>/output/full_lr_predictions/allCA_best_model_128_96_smooth_b05_k5_roi. Point-cloud reconstruction consumes a prediction folder such as <DATA_ROOT>/output/full_lr_predictions/<PREDICTIONS_NAME> plus LR bbox JSONs and raw LR MINC files, then writes <DATA_ROOT>/output/mesoscale_reconstruction/<PREDICTIONS_NAME>/point_cloud.csv.

Maintained region names are RCA1, RCA2, RCA3, and RCA4.

Development

Install the dev dependencies:

uv sync --dev

Use ruff to check and format the code:

uv run ruff check .
uv run ruff format .

Developer reference:

See AGENTS.md for repository-specific development guidance.

License

Original CALHippo source code is released under the Apache License 2.0.

Code authors: Giovanni Casari and Ettore Candeloro, equal contribution.

Model weights, trained checkpoints, datasets, derived annotations, rendered figures, notebook outputs, and other BigBrain-derived artifacts are not covered by the Apache License 2.0. These artifacts are released under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) for non-commercial academic research use only.

Some parts of this repository include copied or modified code from upstream model projects used by the pipeline, including Cellpose, HoVer-Net, InstanSeg, StarDist, and related dependencies. Those files remain subject to their original upstream licenses and copyright notices. Where applicable, upstream notices are retained in the corresponding source folders and/or in THIRD_PARTY_NOTICES.md.

UNI2-h weights are not redistributed by this repository. Users who need the UNI2-h classification path must request access from the upstream provider and authenticate locally.

The CALHippo framework, released weights, and derived artifacts are intended for non-commercial research use and are not intended for clinical diagnosis, medical decision-making, or commercial deployment.

Citations

If you use our dataset/code you must cite the following:

@inproceedings{2026MICCAI_calhippo,
  title={CALHippo: Cell Segmentation for Neuronal Density Inference in the Human Hippocampus},
  author={Casari, Giovanni and Candeloro, Ettore and Gandolfi, Daniela and Mapelli, Jonathan and Bolelli, Federico and Grana, Costantino},
  year={2026},
  month={June},
  book={Medical Image Computing and Computer Assisted Intervention – MICCAI 2026},
  booktitle={Medical Image Computing and Computer Assisted Intervention – MICCAI 2026},
  venue={Strasbourg, France},
  keywords={Human Brain, Cell Segmentation, Density Estimation}
}

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MICCAI 2026 - CALHippo: A reproducible pipeline for cell-type-resolved instance segmentation and density-based mesoscale reconstruction of the human hippocampus.

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