Research Of Quantitative Magnetic Resonance Imaging In Aristocholic Acid Nephropathy

Aristolochic acid nephropathy(AAN),recognized as progressive toxic interstitial nephropathy caused by ingestion of plants containing Aristolochic acid(AA),is the most common nephrotoxicity induced by herbal medicine,particularly in areas where traditional medicine is popular.Serum creatinine(sCr)and blood urea nitrogen(BUN)are considered primary clinical markers for AKI,thus far none of them have been shown to have clinical utility in the detection of AAN or the injury of proximal tubule.Histologic examination remains the mainstay for diagnosis of AAN,which is invasive and susceptible to sampling error.Magnetic resonance imaging(MRI),such as T2 mapping,DWI and QSM,plays an important role in kidney disease for providing physiology and pathophysiology information.AAN was demonstrated a biphasic evolution of renal injury,with the first acute phase characterized by signs of proximal tubular cell swelling and necrosis and chronic phase characterized by proximal tubular atrophy and interstitial fibrosis.Based on the above discoveries,we proposed to investigate renal alterations with qMRI methods as the following work:(1)Assessment of Aristolochic Acid-induced acute kidney injuries in rats with parametric MRI.T2 mapping was employed to assess the kidney changes as it was revealed that T2 values strongly depend on free water content in tissue,hence often considered a marker for quantification of tissue edema.DWI with the quantification of apparent diffusion coefficient(ADC)was shown to provide differenciated information on renal microstructure and function in AKI.This study employed T2 mapping and DWI to detect early renal microstructural alterations and proximal tubular injury induced by AA.Severe renal injury was detected with ADC mapping.T2 values present changes earlier than sCr and BUN,and was significantly correlated with tubular injury score(TIS).(2)Diffusion spectrum analysis of kidney intravoxel incoherent motion based on nonnegative least-squares(NNLS)in AKI.The bi-exponential is considered less suited in the analysis of DWI data of kidey as more than two diffusion component were reported in kidney.In this chapter,the NNLS-based diffusion spectrum analysis,together with mono-exponential and bi-exponential non-linear fitting were employed in the research of AAN rats and AKI patients.Our results show that the reproducibility of the parameters calculated by NNLS-based diffusion spectrum analysis were superior to those calculated by bi-exponential non-linear fitting.NNLS-based diffusion spectrum analysis was the only method that could differentiate the kidney injury induced by AA in all ROIs from the healthy control,and could provide more information of pseudo-diffusion corresponding with tubular flow and vascular perfusion.(3)Kidney QSM method based on dual TR 3D GRE sequence.QSM was reported to be sensitive to kidney fibrosis which is diamagnetic.To solve the challengs of respiratory motion and field perturbation induced by fat,we proposed kidney QSM method based on breath-hold dual TR 3D GRE sequence.In this method,in-phase signals for the initialization of water-fat separation using R2*-IDEAL(iterative decomposition of water and fat with echo asymmetry and least-squares estimation)and the out-phase signals were acquired in consecutive TRs.The invivo results demonstrate that the proposed method was feasible in kidney QSM with a breath-hold of twenty-two seconds,and quantitative susceptibility values,R2*and fat-fraction were obtained simultaneously.