Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

ABSTRACT

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.