PurposeTo explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. Materials and MethodsThis Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. ResultsMean ADC, median ADC, 5(th) percentile ADC, 25(th) percentile ADC, 75(th) percentile ADC, 95(th) percentile ADC (all P < 0.001), and kurtosis (P = 0.001) were significantly lower in malignant thyroid nodules, and mean ADC achieved the highest AUC (0.919) with a cutoff value of 1842.78 x 10(-6) mm(2)/s in differentiating malignant and benign nodules. Compared to the PTCs without extrathyroidal extension, PTCs with extrathyroidal extension showed significantly lower median ADC, 5(th) percentile ADC, and 25(th) percentile ADC. The 5(th) percentile ADC achieved the highest AUC (0.757) with cutoff value of 911.5 x 10(-6) mm(2)/s for differentiating between PTCs with and without extrathyroidal extension. ConclusionWhole-lesion ADC histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555.