Heterogeneity-Aware Deep Learning for Tumour Classification from Multiparametric MRI
Authors: Yue Xia, Euijoon Ahn, Tian Xia, Yuan Yuan, Michael Fulham, Jinman Kim
Organizations: School of Computer Science, The University of Sydney, Camperdown, NSW, 2006, Australia. · Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW, 2006, Australia.
Intra-tumoural heterogeneity (ITH) reflects spatial variation in tumour biology and is an important determinant of tumour behaviour, prognosis, and treatment response. Radiomics and deep learning have shown promise for tumour classification from multiparametric MRI (mp-MRI), but radiomics relies on handcrafted features, while most deep learning methods use whole-tumour representations or manually defined sub-regions, limiting scalable modelling of tumour heterogeneity. We propose a Heterogeneity-Aware Deep Learning Classification (HA-DLC) framework that explicitly models imaging-derived tumour sub-regions for lesion-type diagnosis and molecular-status prediction. HA-DLC consists of: (1) a Heterogeneous Sub-region Generation (HSG) module that produces initial pseudo-labelled sub-regions via unsupervised clustering, followed by Cross-Patient Sub-region Alignment (CPSA), which maps cluster-derived regions to a shared label space using soft assignments; and (2) a Dual-Stream Feature Extraction (DSFE) module that integrates local heterogeneity-aware features with global tumour representations. Given the initial clustering masks, CPSA, segmentation, feature extraction, and classification are jointly optimized end-to-end using soft-target segmentation and classification objectives. We evaluate HA-DLC on the LLD-MMRI2023 liver lesion dataset and the RSNA-ASNR-MICCAI 2021 Radiogenomic Brain Tumour dataset. HA-DLC consistently outperforms state-of-the-art radiomics and deep learning baselines, demonstrating the value of cross-patient sub-region alignment and dual-stream heterogeneity modelling for tumour classification from mp-MRI.
Figures & tables
Figure 1: Overview of Heterogeneity-Aware Deep Learning Classification (HA-DLC) framework. The framework comprises a Heterogeneous Sub-region Generation (HSG) module, Cross-Patient Sub-region Alignment (CPSA) module, and a Dual-Stream Feature Extraction (DSFE) module for heterogeneity-aware tumour classification. n denotes the number of input MRI sequences in mp-MRI. The segmentation loss ( Lseg ) is computed between the aligned sub-region pseudo-labels and the predicted sub-region probabilities, while the classification loss ( Lcls ) is computed between the ground-truth class labels and the predicted class labels.
Figure 2: Heterogeneity feature extraction stream architecture. The stream follows a 3D residual U-Net structure with encoder and decoder branches constructed from residual blocks. Local heterogeneity features are extracted from the outputs of the encoder residual blocks. The residual block denoted by m contains convolutional layers with m output channels. The notation a@b,m denotes a kernel size of a×a×a , a stride of b×b×b , and m output channels.
LLD-MMRI2023 (LLD-M)
BraTS-RC
Method
Accuracy
F1–Kappa average
Accuracy
AUC
Kaggle Leaderboard
0.677±0.036
0.629±0.048
0.624±0.030
0.640±0.036
ViG-S
0.719±0.020
0.681±0.021
0.603±0.023
0.647±0.023
ResNet-50
0.761±0.021
0.725±0.020
0.622±0.031
0.666±0.012
EfficientNet-B7
0.669±0.054
0.610±0.076
0.595±0.063
0.657±0.021
DenseNet-121
0.735±0.057
0.700±0.061
0.603±0.023
0.667±0.028
Table 1: Classification performance comparison with the evaluated methods on the LLD-MMRI2023 (LLD-M) and BraTS-RC datasets. Best results are in bold and second-best are underlined.
Clustering
Parameter
LLD-M (F1–Kappa average)
BraTS-RC (AUC)
k-means
k=3
0.814±0.012
0.678±0.048
k=4
0.805±0.042
0.667±0.021
k=5
0.819±0.033
0.669±0.030
k=6
0.799±0.036
0.667±0.029
k=7
0.809±0.049
0.670±0.024
k=8
0.791±0.027
0.668±0.038
Table 2: Sensitivity of HA-DLC to HSG clustering configuration on LLD-M and BraTS-RC. All configurations were evaluated using the same outer five-fold splits without nested inner selection. Values are cross-validation validation means and population standard deviations across folds. Best result per dataset is in bold.
Sub-region used
LLD-M (F1–Kappa average)
BraTS-RC (AUC)
Whole tumour
0.565±0.036
0.539±0.038
Generated
0.616±0.071
0.576±0.049
Expert-defined
NA
0.558±0.037
Table 3: XGBoost classification results using radiomics features from different tumour sub-regions.
LLD-M (F1–Kappa average)
BraTS-RC (AUC)
Variant
Score
Δ
Score
Δ
HA-DLC (full)
0.819±0.033
—
0.686±0.036
—
Segmentation target
w/o segmentation loss
0.768±0.029
−0.051
0.623±0.054
−0.063
Whole-tumour segmentation
0.802±0.031
−0.017
0.650±0.021
−0.036
Expert-defined sub-regions
NA
—
0.681±0.022
−0.005
Table 4: Ablation study on LLD-M and BraTS-RC (5-fold cross-validation). The upper block varies the segmentation target; the lower block removes one component of HA-DLC at a time. Δ is relative to the full HA-DLC. Best result per dataset in bold.
Figure 3: Sub-region segmentation of liver tumour on T2-weighted MRI. The top two rows show four representative hepatic metastases, with predicted sub-region maps in the first row and the corresponding T2-weighted images in the second row. The bottom two rows show four representative hepatocellular carcinomas (HCC), with predicted sub-region maps in the third row and the corresponding T2-weighted images in the fourth row. The predicted sub-regions are overlaid in semi-transparent colours, illustrating lesion-specific intra-tumoural heterogeneity patterns identified by HA-DLC.
Figure 4: Sub-region segmentation and quantitative comparison by MGMT promoter methylation status. (a) Representative T1-weighted MRI slices of glioblastoma lesions from MGMT-methylated tumours (top row) and MGMT-unmethylated tumours (bottom row). Sub-region 1 is shown in blue and Sub-region 2 in brown. (b) Boxplots of normalised sub-region volume ratios (sub-region volume/total tumour volume), stratified by methylation status (blue boxes: unmethylated; red boxes: methylated).
Precise molecular subtyping of gliomas, including isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion, directly guides surgical and therapeutic decisions, yet currently relies on invasive tissue sampling. Deep learning on structural MRI has emerged as a non-invasive alternative, but anatomy-only approaches cannot capture the hemodynamic signatures that distinguish molecular subtypes. Radiogenomics based on dynamic susceptibility contrast (DSC) MRI holds immense potential for non-invasively characterizing glioma molecular subtypes, yet clinical deployment has been hindered by inter-site variability and the limitations of voxel-wise analysis. We introduce HiPerfGNN, a framework that first learns discrete hemodynamic representations from raw time-intensity curves using a vector-quantized variational autoencoder (VQ-VAE). These quantized perfusion codes define coarse-level graph nodes representing functional tumor habitats, each of which is hierarchically subdivided into fine-level subregions guided by structural MRI. A hierarchical graph neural network then propagates information across scales for molecular prediction. On an internal cohort (n=475), the model achieved AUCs of 0.96 (IDH), 0.89 (1p/19q), and 0.84 (WHO grade), and maintained robust IDH performance (AUC 0.89) on an independent external cohort (n=397) without recalibration. Gradient-based saliency analysis confirms biologically grounded attention patterns aligned with known glioma pathophysiology. Our results demonstrate the added value of integrating perfusion dynamics into radiogenomic pipelines for glioma molecular subtyping. Code is available at https://github.com/janghana/HiPerfGNN.
Han Jang, Junhyeok Lee, Heeseong Eum +4
Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, South Korea · Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, South Korea · Dept. of Biomedical Sciences, Seoul National University, Seoul, South Korea +4
Clinicians diagnose brain tumors by synthesizing patient symptoms, medical history, and quantitative imaging data from modalities such as MRI and CT scans into a unified clinical judgement. However, most deep learning models rely on MRI/CT images alone, failing to replicate the clinicians multimodal reasoning. We explore a two-branch multimodal network combining raw MRI scans with 91 extracted radiomic features (intensity, texture, shape, and boundary descriptors) to classify brain tumors into glioma, meningioma, pituitary, and no-tumor. A pre-trained CNN backbone encodes the image stream, whereas a dedicated MLP encodes the radiomic stream. Both streams are fused via concatenation, gated, or bidirectional cross-modal attention strategies. Across nine experimental runs on a balanced 7,200 image dataset, all multimodal configurations outperform unimodal baselines with gated fusion achieving the best accuracy of 96.13%.
Wajih ul Islam, Muhammad Yaqoob, Javed Ali Khan +1
School of Physics, Engineering and Computer Science, University of Hertfordshire, UK
Modernizing cancer registries with deep learning is opening new opportunities to automate labor-intensive tasks such as the coding of pathology reports. However, progress is constrained by the scarcity of report-level human-annotated training data. Cancer registries generate substantial volumes of expert-assigned labels as a routine product of their operations, but these exist at the patient level and are not linked to the individual pathology reports that informed them, limiting their direct use for training models. We develop an efficient framework for training deep learning classifiers by leveraging these operationally-generated labels without requiring per-report human annotation, demonstrated for tumor group classification at the BC Cancer Registry. We use Attention-Based Multiple Instance Learning (ABMIL) to recover the lost link between patient-level labels and the reports that informed them, leveraging the attention the model places on each report to distil a large, noisily-labeled corpus into a compact, high-quality per-report training dataset. A classifier fine-tuned on a distilled dataset achieved a macro F1 of 0.83, outperforming established baselines across most tumor groups. By turning routine operational labels into high-quality training data without additional annotation or large-scale computing infrastructure, ABMIL offers a practical and accessible route to automating cancer registry workflows.
Leonard Ruocco, Jonathan Simkin, Lovedeep Gondara +2
British Columbia Cancer Registry, Provincial Health Services Authority, Vancouver, Canada · University of British Columbia, Vancouver, Canada · Data Science Institute, University of British Columbia, Vancouver, Canada