NeoNet: An End-to-End 3D MRI-Based Deep Learning Framework for Non-Invasive Prediction of Perineural Invasion via Generation-Driven Classification
Authors: Youngung Han, Minkyung Cha, Kyeonghun Kim, Induk Um, Myeongbin Sho, Joo Young Bae, Jaewon Jung, Jung Hyeok Park, +7 more
Organizations: Seoul National University, South Korea · OUTTA, South Korea · Chung-Ang University, South Korea · Sookmyung Women’s University, South Korea · Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea · Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea · Samsung Changwon Hospital, Sungkyunkwan University School of Medicine · NVIDIA AI Technology Center, Taipei, Taiwan
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.
Figures & tables
Figure 1: Morphological features of perineural invasion (PNI) demonstrated by histopathology (a), CT (b), and MRI (c-PNI negative, d-PNI positive). Arrows indicate the locations of characteristic PNI features in each modality.
Figure 2: Overview of the NeoNet framework. (1) NeoSeg performs automated liver and tumor segmentation on inputs (e.g., 240×240×100 ), producing segmentation labels (e.g., 240×240×100 ). The TLCR algorithm utilizes these labels and the original image to extract localized image and label patches ( 96×96×48 ). (2) NeoGen utilizes a 3D-LDM (Step #1) and trains ControlNet (Step #2) conditioned on label patches to generate synthetic image patches, balancing the dataset. (3) NeoCls utilizes PattenNet, initialized with the frozen LDM encoder ( E ), to predict PNI status from real and synthetic patches.
Figure 3: Architecture of PattenNet for PNI prediction. The model utilizes a frozen encoder from the 3D-LDM followed by two Dual Attention Blocks (DAB). Each DAB integrates 3D channel and spatial attention. Spatial attention utilizes a 3D convolution ( 7×7×7 ) to effectively model 3D spatial relationships. The attended features are processed through global pooling and an MLP for binary classification.
Model
Mean Dice
U-Net
0.9453
SegResNet
0.9416
DynUNet
0.9482
SwinUNETR
0.9516
Table 1: Performance comparison of different segmentation models for liver and tumor segmentation.
Figure 4: Labels generated by NeoSeg. Real Image (left), Segmentation masks (middle: peritumoral mask in red, tumor in yellow), and Overlay (right).
Model
LPIPS ↓
SSIM ↑
PSNR ↑
QNeoGen VQVAE
0.3003
0.4958
15.2210
NeoGen VAE
0.2010
0.7408
22.7427
Table 2: Reconstruction quality comparison between NeoGen VAE and QNeoGen VQVAE.
Method
FID ↓ (A)
FID ↓ (S)
FID ↓ (C)
FID ↓ (Avg.)
QNeoGen DM
18.9751
22.1884
39.2260
26.7965
QNeoGen
14.5820
18.4123
28.6891
20.5611
NeoGen DM
7.6284
10.8560
17.8180
12.1008
NeoGen
2.9440
4.8279
8.2223
5.3314
Table 3: Fréchet Inception Distance (FID) comparison across Axial (A), Sagittal (S), and Coronal (C) views.
Figure 5: Real Patch (a) and Synthetic Patch (b) generated by NeoGen using the corresponding anatomical mask. Morphological features are highlighted by red arrows.
Model (3D)
R (Imbalanced)
R + S (25%)
R + S (50%)
R + S (75%)
R + S (100% Balanced)
ResNet-50
0.6938
0.7388
0.7599
0.7551
0.7618
ResNet-101
0.6284
0.6989
0.7024
0.7117
0.7203
ResNet-152
0.7078
0.7233
0.7421
0.7382
0.7526
ResNet-200
0.6687
0.7250
0.7307
0.7397
0.7412
DenseNet-121
0.6788
0.7443
0.7380
0.7490
0.7551
DenseNet-169
0.6725
0.7021
0.7387
0.7434
0.7584
Table 4: AUC comparison of PNI classifiers trained on different R (Real) to S (Synthetic) ratios using 5-fold cross-validation. R+S columns represent progressive augmentation towards a fully balanced (1:1) dataset (R+S 100% Balanced). Results are presented as Mean AUC. All baseline models are 3D implementations.
Configuration
AUC (R+S)
PattenNet (Full Model, 2 DABs)
0.7903
DAB Component Ablation (2 Blocks)
w/ Channel Attention only
0.7276
w/ Spatial Attention only
0.7410
Number of DABs
0 Blocks (Base LDM Encoder)
0.7001
Table 5: Ablation study evaluating the impact of attention components and the number of Dual Attention Blocks (DABs) in PattenNet.
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.
Youngung Han, Hyunsu Go, Kyeonghun Kim +9
Seoul National University, Seoul, Republic of Korea · OUTTA, Seoul, Republic of Korea · Chung-Ang University, Seoul, Republic of Korea +3
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.
Hyunsu Go, Youngung Han, Kyeonghun Kim +15
Seoul National University, Seoul, Republic of Korea · OUTTA, Seoul, Republic of Korea · Kyung Hee University, Seoul, Republic of Korea +5
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× compared with dense MAC-only computation of the same network.
Youngung Han, Yului Jeong, Kyeonghun Kim +11
Seoul National University, Seoul, Republic of Korea · OUTTA, Seoul, Republic of Korea · Kyung Hee University, Seoul, Republic of Korea +2