Calibrated Selective Prediction Using Deep Ensembles for ROI-Based Thyroid Nodule Ultrasound Classification Under Dataset Shift: A Retrospective Evaluation
Authors: Md. Sadibul Hasan Sadib, Md. Mohayminul Mukit, Rahmatul Kabir Rasel Sarker, Tahmid Alam Tamim, Md. Monir Hossain Shimul
Organizations: Department of Computer Science and Engineering, Daffodil International University, Dhaka, Bangladesh. · Department of Computer Science and Engineering, Daffodil International University, Savar, Dhaka, Bangladesh. · Department of Public Health, Daffodil International University, Dhaka, Bangladesh. · Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, United Kingdom.
Abstract
Background: Deep learning models can classify thyroid nodules on ultrasound, but reliable clinical decision support also requires calibrated probabilities, uncertainty estimation, and selective referral, particularly under dataset shift. Methods: We developed a calibrated deterministic five-member deep ensemble for ROI-based thyroid nodule classification and selective image-based triage. TN5000 was used for model development, five-fold cross-validation, member-wise vector-scaling calibration, and fold-specific threshold selection. TN3K served as an independent external dataset-shift evaluation. The framework used ConvNeXt-Tiny with squeeze-and-excitation attention, ensemble-mean malignancy probability, and mutual information (MI) as an ensemble-disagreement score. A three-tier policy assigned images to No-FNA suggestion, FNA recommendation, or radiologist review. Results: On pooled out-of-fold TN5000 predictions, the ensemble achieved AUC-ROC 0.9395, AP 0.9715, ECE 0.0088, and Brier score 0.0813. At 50% nominal MI retention, 7.2% of cases received a No-FNA suggestion, 39.9% an FNA recommendation, and 52.9% radiologist review, with 98.3% No-FNA NPV and 99.83% malignancy capture. On TN3K, AUC-ROC decreased to 0.7870, AP to 0.7254, ECE increased to 0.1899, and Brier score to 0.2281. The frozen TN5000 policy assigned 83.7% to review, 1.0% to No-FNA, and 15.3% to FNA recommendation. No malignant image entered the No-FNA pathway, but FNA-recommendation PPV fell to 76.6%. Conclusion: The framework showed strong internal discrimination and calibration, but limited external threshold transportability. Selective prediction may help identify images unsuitable for automated triage, but local recalibration, threshold validation, and prospective clinical evaluation are required before deployment.
Thyroid ultrasound diagnosis requires coordinated lesion localization, measurement, risk stratification and reporting, yet most AI systems address these tasks in isolation and provide limited support for clinical review. We present ThyroidXAgent, a clinician-interactive agentic AI system that coordinates specialized diagnostic tools and stores their outputs as an auditable case-level evidence record. The system was developed using OpenThyroidDB, a multicentre, multitask resource integrating approximately 0.3 million ultrasound images and 24,000 paired reports, and was evaluated on 28,458 non-overlapping test cases, including 8,721 cases from 35 centres in the private NHC-MISD-TUS cohort. Across heterogeneous datasets, ThyroidXAgent achieved a mean Dice score of 87.21 percent for nodule segmentation and a mean AUROC of 0.9466 for benign-malignant classification. The same workflow supported lymph-node metastasis prediction and follicular versus papillary thyroid carcinoma classification, with AUROCs of 0.864 and 0.805, respectively. For report generation, evidence-grounded assembly outperformed multimodal language-model baselines across three cohorts. ThyClinScore, a lesion-level clinical semantic metric introduced here, showed the strongest correlation with a location-aware language-model judge. ThyroidXAgent improved physician classification accuracy, increased report diagnostic consistency from 70.3 percent to 86.2 percent, and reduced segmentation and reporting time by 35.9 percent and 27.4 percent, respectively. These findings support auditable, clinician-correctable agentic AI for thyroid ultrasound diagnosis and reporting.
Deep learning (DL) methods dominate thyroid nodule segmentation in ultrasound (US) images, achieving high Dice scores but at the cost of millions of parameters, GPU-dependent training via backpropagation, and limited mathematical tractability. These limitations impede deployment in resource-constrained environments. In this paper, we propose MedSaab-US, a backpropagation-free segmentation framework grounded in the Green Learning paradigm. MedSaab-US extracts multi-scale spatial-frequency features by combining multi-level Discrete Wavelet Transform (DWT) with multi-scale channel-wise Saab (Subspace Approximation with Adjusted Bias) transforms at patch sizes of 5 x 5, 11 x 11, and 21 x 21 pixels. Label-Assisted Greedy (LAG) feature selection retains the most discriminative features, which are fed to an XGBoost classifier for pixel-wise prediction. The Saab transform parameters are determined analytically from data statistics, while XGBoost employs iterative greedy tree construction without requiring backpropagation. Evaluated on the TN3K dataset (2,879 training and 614 test images), MedSaab-US achieves a mean Dice coefficient of 0.4784 +/- 0.2190, precision of 0.5768, and recall of 0.5604, with a model footprint under 500K parameters and CPU-only inference in approximately 0.3 seconds per image. We present this result as an exploratory non-DL baseline for thyroid ultrasound segmentation and analyze the specific challenges posed by isoechoic nodules. An ablation study further quantifies the contribution of each pipeline component, including separate evaluations of LAG feature selection and training-set size.
Pulmonary nodule malignancy prediction typically depends on image-trained specialist deep learning (DL) models that require substantial annotated imaging data and task-specific training. We investigate whether a generalist large language model (LLM), reading only a faithful natural-language rendering of standard nodule attributes, can serve as a calibrated triage layer. We propose ConfTriage, a confidence-calibrated method built on three pillars: language as the modality, calibration as the safety mechanism, and a selective specialist DL backstop for low-confidence cases. We prove two guarantees: a finite-sample combined-error bound yielding an explicit per-threshold operational certificate, and an oracle inequality showing that excess risk over the Bayes-optimal deferral classifier is controlled by the L1 calibration error of the LLM probability. A controlled seven-way input ablation across five frontier LLMs on LIDC-IDRI shows that natural-language descriptions dominate the diagnostic signal, while low-level image statistics are essentially diagnostically vacuous. ConfTriage achieved an F1 score of 88.22% and an AUC of 0.92, resolving 76.5% of cases using zero-shot LLM inference alone and referring only uncertain cases to the specialist DL backstop. These results demonstrate that clinically meaningful diagnostic information can be captured through structured radiological descriptions and leveraged by calibrated LLMs for selective referral. The framework suggests a practical pathway for combining generalist LLM prediction with specialist AI models in medical decision-support systems. Source code is publicly available at https://github.com/rabiul-ai/ConfTriage.