Order-Aware 2.5D Multiple Instance Learning for Preoperative MRI-Based Perineural Invasion Risk Assessment in Intrahepatic Cholangiocarcinoma

Perineural invasion (PNI) is associated with poor postoperative outcomes in intrahepatic cholangiocarcinoma, but it is confirmed by surgical pathology. Existing preoperative imaging models often rely on radiologist-defined variables, contrast-enhanced imaging, or manual annotations. We propose an anatomy-privileged teacher--student framework for patient-level PNI prediction from T2-weighted MRI. During training, the teacher uses MRI with tumor and liver masks to learn dense token routing, and the student distills this guidance to retain and aggregate informative tokens under a fixed budget. Anatomical supervision is restricted to training, and the deployed model does not require masks at inference. In 155 patients, the proposed method achieved the highest mean AUROC of 0.750 among matched MRI-only baselines evaluated under the same protocol, with 1.43 GFLOPs and 8.02 ms per case on a Jetson Orin Nano Super Developer Kit.

Perineural invasion (PNI) is a clinically relevant indicator of tumor aggressiveness and can influence surgical decision-making, motivating interest in reliable preoperative assessment. The subtle MRI features of PNI, however, often resemble nearby anatomy, complicating noninvasive prediction. These fine perineural cues are easily attenuated by routine downsampling or overly global feature aggregation, reducing the effectiveness of conventional volumetric models. We present LoSA-Net, a localized and scale-adaptive architecture for boundary-sensitive PNI prediction in 3D MRI. Talking Neighborhood Attention (TNA) preserves nerve-aligned detail through localized self-attention with head-wise mixing, and Scale-Adaptive Feature Mixing (SAFM) modulates the receptive field using multi-scale depthwise processing. Cross-Scale Refinement and Alignment (CSRA) maintains consistency between semantic context and high-resolution boundaries across stages. In contrast-enhanced MRI scans from 168 patients with cholangiocarcinoma, LoSA-Net achieves an AUC of 0.7567 and outperforms representative convolutional and transformer baselines under matched preprocessing and optimization settings.

Preoperative prediction of perineural invasion (PNI) in cholangiocarcinoma (CCA) is clinically valuable but remains challenging because PNI-related cues on magnetic resonance imaging (MRI) are subtle, sparse, and spatially localized around the tumor boundary. Standard 3D CNN and transformer architectures process volumetric data in a dense or spatially uniform manner, which can dilute subtle PNI-related evidence while requiring a large number of multiply-accumulate operations over 3D feature grids. To address these limitations, we propose SCINTILLA-SNN, a 3D spiking network composed of a four-stage hierarchical backbone and a Multi-Scale Spike Aggregation (MSSA) module for PNI prediction. The backbone extracts hierarchical volumetric representations through spiking convolutional stages and local spike window modulation stages. Given the resulting stage-wise representations, MSSA maps each spatial token to a learnable content value and modulates it with a spike-dynamics gate derived from firing rate and timestep-wise membrane-potential variability. The resulting score, referred to as the diagnostic token score, is used to selectively aggregate sparse PNI-related evidence. Experiments on a 10-year retrospective cohort of 182 CCA patients show that SCINTILLA-SNN achieves an AUROC of 0.748 under 5-fold cross-validation, while reducing the estimated inference energy by 23.18$\times$ compared with dense MAC-only computation of the same network.