NaGdF4 Nanoprobe-Enhanced Multiparametric MRI for Evaluating Diabetes Mellitus-Associated Hepatic Dysfunction and Precancerous Biliary Transformation

Type 2 diabetes mellitus (T2DM) has evolved into a global health crisis, driving a silent yet progressive hepatic pathological cascade that advances from nonalcoholic fatty liver disease to fibrosis and ultimately to cholangiocarcinoma with a high probability. However, the covert nature and gradual progression of this pathological cascade pose significant challenges for early detection and continuous monitoring. Herein, we design a multiparameter magnetic resonance imaging (MRI) strategy for visually monitoring T2DM-associated hepatic dysfunction across disease stages in vivo, based on dual-modality NaGdF4 nanoprobes. Owing to the long tumbling time (τR), NaGdF4 nanoprobes can enhance longitudinal relaxivity (r1) to brighten T1-weighted signals, while the regular arrangement of Gd3+ in the crystal induces magnetic anisotropy, creating local static magnetic field heterogeneity that generates negative signals in susceptibility-weighted imaging (SWI) sequences. The multiparametric MRI strategy combined with pathological analysis comprehensively characterized hepatic disease progression in a T2DM mouse model and confirmed the association between T2DM-induced liver injury and precancerous biliary transformation. With the NaGdF4 nanoprobes, key imaging features were successfully identified, including impaired hepatic metabolic capacity with prolonged contrast retention, hypoxia-induced neovascularization, and biliary tract lesions progressing from intermediate reactive hyperplasia to advanced cholangiocarcinoma. This multiparameter MRI approach provides noninvasive, high-resolution insights into hepatic metabolic dysfunction, vascular remodeling, and biliary pathology, offering a powerful tool for early diagnosis and prognostic assessment of T2DM-associated liver complications.