C2LUE: Clinically Aligned Patient-Level Ultrasound Diagnosis via Evidence-Aware Multi-Instance Learning
Authors: Qin-Yi Zhang, Linying Cao, De-Xing Huang, Haichuan Lin, Yi Yang, Manzhi Wang, Xiao-Hu Zhou, Chen Chen, +2 more
Organizations: State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China · School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China
Patient-level ultrasound diagnosis demands not only high predictive accuracy but also clinically aligned mitigation of asymmetric diagnostic risks. While Multi-Instance Learning (MIL) effectively models routine multi-view exams, standard aggregators often dilute heterogeneous diagnostic cues and optimize solely for global accuracy. This frequently yields undesirable sensitivity-specificity trade-offs. To bridge this gap, we propose C2LUE, a novel MIL framework coupling evidence aware aggregation with risk-aligned regularization. To preserve evidence heterogeneity and prevent unimodal attention collapse, C2LUE employs a multi-query cross-attention mechanism built upon a LoRA-adapted DINOv3 backbone. Multiple latent queries explicitly extract and disentangle diverse morphological patterns from the ultrasound sequence. Furthermore, to improve clinical risk alignment, we introduce a dynamic trade-off regularization objective that penalizes sensitivity-specificity imbalance during training. Rather than leaving the clinical trade-off entirely to post-hoc threshold adjustment, this objective encourages the learned score distribution toward a more balanced operating region. Extensive evaluations on patient-level, biopsy-proven thyroid and breast ultrasound datasets demonstrate that C2LUE consistently outperforms prior alternatives. By uniting strong discrimination with a balanced error profile, C2LUE provides a promising solution for real-world ultrasound screening and diagnosis.
Figures & tables
Figure 1: Overview of C 2 LUE. (a) The evidence-aware pipeline extracts heterogeneous features via multi-query cross-attention on a LoRA-adapted DINOv3 backbone. (b) The clinical objective dynamically penalizes sensitivity-specificity imbalance to align the decision boundary with clinical trade-off preferences.
Dataset
Split
Images
Patients
Benign
Malignant
Bag size
ThyroidXL
Train
9,541
3,354
2,477
877
2.85/3 [1, 10]
Val
2,094
739
386
353
2.83/3 [1, 8]
BUS-BRA
Train
1,323
744
505
239
1.78/2 [1, 2]
Test
552
320
217
103
1.73/2 [1, 2]
Table 1: Patient-level dataset statistics. Bag size is reported as mean/median [min, max].
Method
ThyroidXL
BUS-BRA
AUC
AUPRC
Se
Sp
AUC
AUPRC
Se
Sp
MeanP
0.912 ± 0.004
0.905 ± 0.006
0.745 ± 0.005
0.909 ± 0.007
0.929 ± 0.005
0.868 ± 0.004
0.718 ± 0.006
0.912 ± 0.008
MaxP
0.916 ± 0.009
0.876 ± 0.007
0.618 ± 0.005
0.941 ± 0.004
0.927 ± 0.006
0.865 ± 0.004
0.670 ± 0.005
0.923 ± 0.007
WMV
0.918 ± 0.005
0.874 ± 0.006
0.686 ± 0.004
0.940 ± 0.003
0.925 ± 0.007
0.869 ± 0.005
0.718 ± 0.006
0.922 ± 0.004
ABMIL
0.922 ± 0.006
0.913 ± 0.004
0.785 ± 0.008
0.902 ± 0.005
0.922 ± 0.004
0.871 ± 0.007
0.689 ± 0.003
0.908 ± 0.006
GatedMIL
0.924 ± 0.004
0.911 ± 0.005
0.708 ± 0.007
0.922 ± 0.006
0.917 ± 0.005
0.870 ± 0.006
0.748 ± 0.004
0.899 ± 0.008
Table 2: Main results (mean ± std, 5 seeds). Δ shows the gain of our method vs . the second-best method. Gray value shows the decrease compared to the best method.
Figure 2: Decision Boundary Alignment. Left: sensitivity–specificity trade-off. Right: representative single-run confusion matrices; parentheses denote changes relative to the baseline.
Figure 3: Multi-query evidence visualization. Top: query-specific attention of representative queries across instances. Bottom: complementary diagnostic regions highlighted by different queries.
Setting
ThyroidXL
BUS-BRA
AUC
AUPRC
Se
Sp
AUC
AUPRC
Se
Sp
Evidence Aggregation Strategy
Q=1
0.916 ± 0.005
0.902 ± 0.004
0.853 ± 0.006
0.852 ± 0.007
0.887 ± 0.004
0.808 ± 0.005
0.825 ± 0.006
0.820 ± 0.004
Q=8
0.914 ± 0.006
0.889 ± 0.005
0.853 ± 0.004
0.855 ± 0.003
0.888 ± 0.007
0.821 ± 0.006
0.824 ± 0.005
0.834 ± 0.008
Q=4 ✓
0.932 ± 0.003
0.919 ± 0.004
0.874 ± 0.004
0.876 ± 0.003
0.936 ± 0.002
0.880 ± 0.005
0.876 ± 0.005
0.879 ± 0.003
Δ +0.016
+0.017
+0.021
+0.021
Δ +0.048
+0.059
+0.051
+0.045
Table 3: Ablation study on patient-level performance (mean ± std, 5 seeds). Δ shows the gain of ours relative to the second-best setting within each ablation block. Gray value shows the decrease compared to the best setting.
Figure 4: View-availability analysis on (a) ThyroidXL and (b) BUS-BRA. Patient-level performance improves as more ultrasound views are available. Error bars denote standard deviations over five random seeds.
Vision-Language Models (VLMs) have significantly advanced medical visual question answering, yet their performance in ultrasound remains suboptimal. In clinical practice, sonographers explicitly focus on lesion regions to formulate reports, though diagnostic interpretations sometimes vary due to inherent subjectivity. However, existing VLMs are not explicitly structured to interactively zoom into lesions prior to diagnosis; moreover, they typically treat annotations as unbiased ground truths, failing to account for their inherent subjectivity and ambiguity. In this paper, we propose a framework specifically designed to consider the sonographer's cognitive workflow. We first introduce a structured Zoom-then-Diagnose paradigm, which replicates the interactive search process to enable lesion-focused reasoning. Furthermore, within the Group Relative Policy Optimization (GRPO) framework, we introduce an uncertainty-aware reward derived from stochastic group-wise rollouts to estimate prediction consistency as a proxy for model confidence. Together, these two components encourage the model to reinforce accurate predictions on clear cases while remaining cautious under ambiguity. Experiments across liver, breast, and thyroid datasets show that our framework improves lesion localization by 39.3%, demonstrating that our model has learned the ability to actively look closer and diagnose.
Yue Zhou, Erxuan Wu, Yikang Sun +5
Computer Aided Medical Procedures (CAMP), TU Munich, Germany · Munich Center for Machine Learning (MCML), Munich, Germany · Zhongshan Hospital, Fudan University, China +1
Ultrasound interpretation requires both precise lesion localization and holistic clinical reasoning, yet existing methods typically excel at only one of these capabilities: specialized detectors offer strong localization but limited reasoning, whereas multimodal large language models (MLLMs) provide flexible reasoning but weak grounding in specialized medical domains. We present Echo-α, an agentic multimodal reasoning model for ultrasound interpretation that unifies these strengths within an invoke-and-reason framework. Echo-α is trained to coordinate organ-specific detector outputs, integrate them with global visual context, and convert the resulting evidence into grounded diagnostic decisions beyond detector-only inference. This behavior is established through a nine-task supervised curriculum and then refined by sequential reinforcement learning under different reward trade-offs, yielding Echo-α-Grounding for lesion anchoring and Echo-α-Diagnosis for final diagnosis. On multi-center renal and breast ultrasound benchmarks, Echo-α outperforms competitive baselines on both grounding and diagnosis. In particular, on cross-center test sets, Echo-α-Grounding attains 56.73%/43.78% [email protected] and Echo- α-Diagnosis reaches 74.90%/49.20% overall accuracy on renal/breast ultrasound. These results suggest that agentic multimodal reasoning can turn specialized detectors into verifiable clinical evidence, offering a practical route toward ultrasound AI systems that are more accurate, interpretable, and transferable. The repository is at https://github.com/MiliLab/Echo-Alpha.
Jing Zhang, Wentao Jiang, Tao Huang +8
School of Computer Science, Wuhan University, China · The Central Hospital of Wuhan, China · Taizhou Hospital of Zhejiang Province, China +1
Large vision-language models (LVLMs) have achieved strong performance across many medical imaging tasks, yet their application to ultrasound remains limited due to its inherent complexity and variability. In this work, we revisit what is truly needed to enable real-world ultrasound understanding. Instead of introducing complex architectures or elaborate training strategies, we show that data scale and clinically faithful data alignment are the key factors. We construct a large-scale dataset of 1.5M real-world ultrasound examinations, containing 17.7M images, multi-organ coverage, and paired uncurated clinical reports. Crucially, we organize the data at the examination level, aligning multiple images with their corresponding reports to reflect real clinical workflows. We then fine-tune a standard LVLM using low-rank adaptation (LoRA) on this dataset without task-specific modifications. Surprisingly, this simple recipe already leads to strong performance across diverse ultrasound understanding tasks, outperforming prior methods designed with more complex pipelines. Beyond these results, we present model and data scaling analyses that provide insights into the role of scale in ultrasound LVLMs.
Bingcong Yan, Chunlei Li, Jingliang Hu +3
1MedAI Technology (Wuxi) Co. Ltd. · 2Technical University of Munich