Quantitative Ultrasound-Based Precision Diagnosis of Papillary, Follicular, and Medullary Thyroid Carcinomas Using Morphological, Structural, and Textural Features.

: Thyroid cancer encompasses distinct histological subtypes with varying biological behavior and treatment implications. Accurate preoperative subtype differentiation remains challenging. Although ultrasound (US) is widely used for thyroid nodule evaluation, qualitative assessment alone is often insufficient to distinguish between papillary (PTC), follicular (FTC), and medullary thyroid carcinoma (MTC). A retrospective analysis was performed on patients with histologically confirmed PTC, FTC, or MTC. A total of 224 standardized B-mode ultrasound images were analyzed. A set of fully quantitative features was extracted, including morphological characteristics (aspect ratio and perimeter-to-area ratio), internal echotexture (echogenicity and local entropy), boundary sharpness (gradient measures and KL divergence), and structural components (calcifications and cystic areas). Feature extraction was conducted using semi-automatic algorithms implemented in MATLAB. Statistical differences were assessed using the Kruskal-Wallis and Dunn-Šidák tests. A Random Forest classifier was trained and evaluated to determine the discriminatory performance of individual and combined features. Significant differences ( < 0.05) were found among subtypes for key features such as perimeter-to-area ratio, normalized echogenicity, and calcification pattern. The full-feature Random Forest model achieved an overall classification accuracy of 89.3%, with F1-scores of 93.4% for PTC, 85.7% for MTC, and 69.1% for FTC. A reduced model using the top 10 features yielded an even higher accuracy of 91.8%, confirming the robustness and clinical relevance of the selected parameters. Subtype classification of thyroid cancer was effectively performed using quantitative ultrasound features and machine learning. The results suggest that biologically interpretable image-derived metrics may assist in preoperative decision-making and potentially reduce the reliance on invasive diagnostic procedures.