A Noninvasive Assessment of Tumor Proliferation in Lung cancer Patients using Intravoxel Incoherent Motion Magnetic Resonance Imaging

Ki-67 is a nuclear antigen widely used in routine pathologic analyses as a tumor cell proliferation marker for lung cancer. However, Ki-67 expression analyses using immunohistochemistry (IHC) are invasive and frequently influenced by tissue sampling quality. In this study, we assessed the feasibility of noninvasive magnetic resonance imaging (MRI) in predicting the Ki-67 labeling indices (LIs). A total of 51 lung cancer patients, including 42 non-small cell lung cancer (NSCLC) cases and nine small cell lung cancer (SCLC) cases, were enrolled in this study. Quantitative MRI parameters from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) were obtained, and their correlations with tumor tissue Ki-67 expression were analyzed. We found that the true diffusion coefficient (D value) from IVIM was negatively correlated with Ki-67 expression (Spearman r = -0.76, P < 0.001). The D values in the high Ki-67 group were significantly lower than those in the low Ki-67 group (0.90 ± 0.21 × 10-3 mm2/s vs. 1.22 ± 0.30 × 10-3 mm2/s). Among three MRI techniques used, D values from IVIM showed the best performance for distinguishing the high Ki-67 group from low Ki-67 group in receiver operating characteristic (ROC) analysis with an area under the ROC curve (AUROC) of 0.85 (95% CI: 0.73-0.97, P < 0.05). Moreover, D values performed well for differentiating SCLC from NSCLC with an AUROC of 0.82 (95% CI: 0.68-0.90), Youden index of 0.72, and F1 score of 0.81. In conclusion, D values were negatively correlated with Ki-67 expression in lung cancer tissues and can be used to distinguish high from low proliferation statuses, as well as SCLC from NSCLC.