Challenges in Deep Learning-Based Small Organ Segmentation: A Benchmarking Perspective for Medical Research with Limited Datasets

Accurate segmentation of carotid artery structures in histopathological images is vital for cardiovascular disease research. This study systematically evaluates ten deep learning segmentation models including classical architectures, modern CNNs, a Vision Transformer, and foundation models, on a limited dataset of nine cardiovascular histology images. We conducted ablation studies on data augmentation, input resolution, and random seed stability to quantify sources of variance. Evaluation on an independent generalization dataset (N=153) under distribution shift reveals that foundation models maintain performance while classical architectures fail, and that rankings change substantially between in-distribution and out-of-distribution settings. Training on the second dataset at varying sample sizes reveals dataset-specific ranking hierarchies confirming that model rankings are not generalizable across datasets. Despite rigorous Bayesian hyperparameter optimization, model performance remains highly sensitive to data splits. The bootstrap analysis reveals substantially overlapping confidence intervals among top models, with differences driven more by statistical noise than algorithmic superiority. This instability exposes limitations of standard benchmarking in low-data clinical settings and challenges assumptions that performance rankings reflect clinical utility. We advocate for uncertainty-aware evaluation in low-data clinical research scenarios from two perspectives. First, the scenario is not niche and is rather widely spread; and second, it enables pursuing or discontinuing research tracks with limited datasets from incipient stages of observations.