Perineural Invasion Prediction

Perineural invasion (PNI) is an adverse histopathologic marker in intrahepatic cholangiocarcinoma (ICC), but it is usually confirmed only after resection. Preoperative T2-weighted MRI may provide noninvasive imaging cues predictive of PNI, although labels are available only at the patient level without slice- or voxel-level annotations. We propose Order-Aware Slab Multiple Instance Learning (OAS-MIL), a weakly supervised framework for patient-level PNI prediction. Each tumor-centered MRI crop is represented as an ordered sequence of overlapping 2.5D slabs formed from contiguous axial slices. A shared encoder extracts slab-level features, which are aggregated by a permutation-invariant set-attention branch and a bidirectional sequence-attention branch. Using five-fold label-stratified cross-validation at the patient level, OAS-MIL achieved a mean AUROC of 0.770, outperforming the evaluated volumetric and MIL baselines. These results suggest that axial order provides a useful inductive bias for weakly supervised PNI prediction from MRI.

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.

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 associated with poor prognosis in cholangiocarcinoma (CCA). However, its detection from 3D MRI remains challenging due to the subtle and spatially heterogeneous imaging signatures at the tumor periphery. Capturing such spatially sparse cues necessitates volumetric analysis of 3D MRI, but existing deep learning approaches incur prohibitive computational costs on volumetric medical images, limiting their clinical deployment. We propose Dual Sparsity Spikformer (SpikeDS), a spiking neural network architecture that jointly exploits activation sparsity from binary spike communication and spatial sparsity from window pruning based on firing rates. SpikeDS introduces Dual Sparsity Spiking Attention (DSSA), which combines two complementary mechanisms. The first is Window-based Expert Mixture Spiking Attention (W-EMSA), which selectively applies attention only to salient windows identified by their firing rates. The second is Cross-Window Spiking Self-Attention (CW-SSA), which enables global context exchange through an asymmetric scheme in which pruned windows still contribute as key-value sources. Evaluated on a clinical cohort of 139 CCA patients via 5-fold cross-validation, SpikeDS achieves an AUC of 0.753 while consuming only 14.4 mJ, surpassing the best baseline in both AUC and energy efficiency. These results suggest that dual sparsity provides an effective hardware-aware strategy for improving the efficiency of 3D spiking transformers without compromising diagnostic performance.

Perineural invasion (PNI) is a critical prognostic factor in cholangiocarcinoma. However, its preoperative prediction from magnetic resonance imaging (MRI) remains challenging due to subtle imaging features that extend beyond tumor boundaries into surrounding regions. Conventional convolutional neural networks are limited in capturing long-range spatial dependencies. Transformer-based architectures improve global modeling of volumetric MRI by aggregating spatially distributed contextual cues, yet capturing subtle and noise-sensitive patterns in peritumoral regions remains challenging. Diffusion-based classifiers offer an alternative formulation by leveraging denoising-based class scoring to better capture such subtle patterns. However, these approaches introduce substantial computational overhead due to the combination of transformer-based modeling and iterative denoising processes. To address these challenges, we formulate PNI prediction as a diffusion-based classification problem and implement the denoising network using a transformer-based representation. To improve computational efficiency, we introduce adaptive routing across attention heads, spatial tokens, and MLP width. Experimental results demonstrate that the proposed approach achieves an AUC of 0.731 with 257.57 GFLOPs.

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.

Perineural invasion (PNI) is a critical prognostic factor in cholangiocarcinoma. Non-invasive prediction from 3D MRI is challenging, demanding models that efficiently capture both fine-grained details and global context. We propose the Multi-window Mixture-of-Head Attention Transformer (MMA-Former), a novel end-to-end 3D architecture featuring a Coarse-Fine Transformer (CFT) structure for parallel multi-scale feature extraction. We advance this structure by integrating a novel Window-Specific Mixture-of-Head attention (WS-MoH) mechanism. Unlike standard Multi-Head Self Attention (MSA), WS-MoH generates a representation for each 3D window and dynamically routes the entire window to specialized or common attention heads. This enables spatially adaptive feature extraction tailored to the local context of each window, enhancing specialization and reducing redundancy without increasing parameters. Evaluated on a retrospective dataset of 168 T1-weighted MRI scans, MMA-Former achieved an AUC of 0.752, outperforming other 3D architectures, including the best CNN (AUC of 0.708) and Transformer baselines (AUC of 0.681).

Minimizing invasive diagnostic procedures to reduce the risk of patient injury and infection is a central goal in medical imaging. And yet, noninvasive diagnosis of perineural invasion (PNI), a critical prognostic factor involving infiltration of tumor cells along the surrounding nerve, still remains challenging, due to the lack of clear and consistent imaging criteria criteria for identifying PNI. To address this challenge, we present NeoNet, an integrated end-to-end 3D deep learning framework for PNI prediction in cholangiocarcinoma that does not rely on predefined image features. NeoNet integrates three modules: (1) NeoSeg, utilizing a Tumor-Localized ROI Crop (TLCR) algorithm; (2) NeoGen, a 3D Latent Diffusion Model (LDM) with ControlNet, conditioned on anatomical masks to generate synthetic image patches, specifically balancing the dataset to a 1:1 ratio; and (3) NeoCls, the final prediction module. For NeoCls, we developed the PNI-Attention Network (PattenNet), which uses the frozen LDM encoder and specialized 3D Dual Attention Blocks (DAB) designed to detect subtle intensity variations and spatial patterns indicative of PNI. In 5-fold cross-validation, NeoNet outperformed baseline 3D models and achieved the highest performance with a maximum AUC of 0.7903.

Diagnostic grading of prostate cancer (PCa) relies on the examination of 2D histology sections. However, the limited sampling of specimens afforded by 2D histopathology, and ambiguities when viewing 2D cross-sections, can lead to suboptimal treatment decisions. Recent studies have shown that 3D histomorphometric analysis of glands and nuclei can improve PCa risk assessment compared to analogous 2D features. Here, we expand on these efforts by developing an analytical pipeline to extract 3D features related to perineural invasion (PNI) and lymphovascular invasion (LVI), which correlate with poor prognosis for a variety of cancers. A 3D segmentation model (nnU-Net) was trained to segment nerves and vessels in 3D datasets of archived prostatectomy specimens that were optically cleared, labeled with a fluorescent analog of H&E, and imaged with open-top light-sheet (OTLS) microscopy. PNI- and LVI-related features, including metrics describing cancer-nerve and cancer-vessel proximity, were then extracted based on the 3D nerve/vessel segmentation masks in conjunction with 3D masks of cancer-enriched regions. As a preliminary exploration of the prognostic value of these features, we trained a supervised machine learning classifier to predict 5-year biochemical recurrence (BCR) outcomes, finding that 3D PNI-related features are moderately prognostic and outperform 2D PNI-related features (AUC = 0.71 vs. 0.52). Source code is available at https://github.com/sarahrahsl/SegCIA.git.