Evaluation Of Acute Aristolochic Acid Nephropathy In Rat Model With 7T MRI

Part 1 Evaluation of acute aristolochic acid nephropathy in rat model by using high resolution 3D-T2WI at 7.0TObjective To evaluate the changes of morphology in acute aristolochic acid nephropathy(AAN)rats by using high resolution three-dimensional T2-weighted imging(HR 3D-T2WI)at 7.0T.Methods Wistar rats were randomly divided into AAN group(n=18)and control group(n=6),which were treated with 40mg/(kg·d)AAI or PEG400 respectively by intraperitoneal injection for 6 days.Six rats per group underwent HR 3D-T2WI scan before and 2,4,6 days after injection.The changes of signal in cortex(CO),outer stripe of the outer medulla(OSOM),inner stripe of the outer medulla(ISOM),inner medulla(IM)were observed.Histological evaluation was performed on 3 rats of AAN group at each time point of MR scan and control group on day 6 after injection.Results The four stripes of rat kidney parenchyma were clear on AAN group’s baseline and control group’s all time points,with moderate or slightly high signal in CO,hypointensive signal in OSOM,slightly hyperintense in ISOM and high signal in IM on HR 3D-T2WI.In AAN group,the structure of each layer is poorly stratified on day2,day4 and day6.Signals in CO and OSOM increased gradually,but it decreased in ISOM and IM on day6.In control group,no significant signal changes were discovered in cortex and medulla during the whole experiment.There were minor injuries observed on day2.On day4 and day6,renal histology was characterized by necrosis of tubular epithelium and loss of brush border in AAN group.Conclusion The changes of renal morphology of AAN rats were evaluated by using HR 3D-T2WI non-invasively,which can provide anatomical information to clinicist.Part 2 Evaluation of acute aristolochic acid nephropathy in rat model by using T1-mapping at 7.0TObjective To evaluate the changes of acute aristolochic acid nephropathy(AAN)in rat model by using T1-mapping at 7.0T.Methods Wistar rats were randomly divided into AAN group(n=18)and control group(n=6),which were treated with 40mg/(kg·d)AAI or PEG400 respectively by intraperitoneal injection for 6 days.Six rats per group underwent T1-mapping scan before(baseline)and 2,4,6 days after injection.The values of cortex(CO),outer stripe of the outer medulla(OSOM),inner stripe of the outer medulla(ISOM),inner medulla(IM)were measured.Histological evaluation was performed on 3 rats of AAN group at each timepoint of MR scan and control group on day 6 after injection.Results The T1-relaxation times of CO in AAN group rats were higher than those of control group on day4(P<0.001)and day6(P<0.001),while the T1-relaxation times of OSOM were higher on all time points(Pday2<0.01,Pday4<0.001,Pday6<0.001)except baseline(P>0.05).However,it was lower in ISOM and IM on day6(PISOM<0.001、PIM<0.O1).In AAN group,there was no obvious changes of cortical T1-relaxation times between day2 and baseline,but it increased on day4(P<0.001)and day6(P<0.001).T1-relaxation times in OSOM raised gradually(P P<0.001 for day2 vs baseline,P<0.001 for day4 vs baseline,P<0.001 for day6 vs baseline).In control group,no significant changes were detected in T1-relaxation times of the four stripes of rat kidney parenchyma during the whole experiment.There were minor injuries observed on day2.On day4 and day6,renal histology was characterized by necrosis of tubular epithelium and loss of brush border in AAN group.No fibrosis was founded in all rats.Conclusion The dynamic changes of acute AAN could be evaluated by using Tl-mapping non-invasively,which can provide useful information for early renal injury.Part 3 Evaluation of renal oxygenation in acute aristolochic acid nephropathy in rat model by using BOLD MRI at 7.0TObjective To evaluate the changes of renal oxygenation in rats of acute aristolochic acid nephropathy(AAN)by using blood oxygenation level dependent(BOLD)MRI at 7.0T.Methods Wistar rats were randomly divided into AAN group(n=18)and control group(n=6),which were treated with 40mg/(kg·d)AAI or PEG400 respectively by intraperitoneal injection for 6 days.Six rats per group underwent BOLD MRI scan before and 2,4,6 days after injection.Cortical and medullary R2*values were measured.Histological and immunohistochemical evaluation was performed on 3 rats of AAN group at each timepoint of MR scan and control group on day 6 after injection.Results Cortical and medullary R2*values of AAN group rats were higher than those of control group on day4 and day6(P<0.05).In AAN group,there was no obvious changes of cortical R2*values between day2 and baseline,but it increased on day4(P<0.05)and day6(P<0.01).Medullary R2*values raised gradually(P>0.05 for day2 vs baseline,P<0.01 for day4 vs baseline,P<0.01 for day6 vs baseline).In control group,no significant changes were detected in R2*values of cortex and medulla during the whole experiment.There were minor injuries observed on day2.On day4 and day6,renal histology was characterized by necrosis of tubular epithelium and loss of brush border in AAN group.Immunohistochemistry revealed that the main expression of HIF-1α protein was in cytoplasmic in the proximal convoluted tubule.As AAN progressed,HIF-1α protein was transferred to nuclear in response to hypoxia.Conclusion The changes of renal oxygenation level of AAN rats were evaluated by using BOLD MRI non-invasively,which can provide useful information for clinical treatment decision.