Rationale and objectivesTo compare the performance of SS, FOCUS SS, MUSE, and FOCUS MUSE DWI for pulmonary lesions to obtain a better technique for pulmonary DWI imaging. Materials and methods44 patients with pulmonary lesions were recruited to perform pulmonary DWI using SS, FOCUS SS, MUSE, and FOCUS MUSE sequences. Then, two radiologists with 12 and 10 years of chest MRI experiences assessed the overall image quality while another two radiologists both with 3 years of experiences evaluated the SNR, DR, and ADC of pulmonary lesions. Using interclass correlation coefficient (ICC) and kappa statistics to assess consistency of readers, Friedman test and Dunn-Bonferroni post hoc were used to calculate the difference between sequences. Mann-Whitney test and ROC curve were used to distinguish malignant from benign lesions. ResultsAll the assessed variables of the four sequences presented good to excellent intra-/inter-observer consistency. Compared with SS, FOCUS SS and MUSE, FOCUS MUSE demonstrated better image quality, including significantly higher 5-point Likert scale score (P < 0.001) and smaller DR (P < 0.001). SNR was comparable among SS, FOCUS SS, and FOCUS MUSE (P > 0.05) while MUSE presented with significantly higher SNR over them (P < 0.01). ADC of malignant was significantly smaller than that of benign for all the four sequences (P < 0.05). ROC analysis showed relatively better diagnostic performance of FOCUS MUSE (AUC = 0.820) over SS (AUC = 0.748), FOCUS SS (AUC = 0.778), and MUSE (AUC = 0.729) in distinguishing malignant from benign lesions. ConclusionFOCUS MUSE possessed sufficient SNR and was better over SS, FOUCS SS, and MUSE for characterizing pulmonary lesions.