title: T2 relaxation time and apparent diffusion coefficient for noninvasive assessment of renal pathology after acute kidney injury in mice: comparison with histopathology.
abstract: BACKGROUND
  Renal ischemia reperfusion injury leads to acute kidney injury (AKI) and is associated with tissue edema, inflammatory cell infiltration, and subsequent development of interstitial renal fibrosis and tubular atrophy. The purpose of this study was to investigate the value of the functional magnetic resonance imaging (MRI) techniques, T2 mapping, and diffusion-weighted imaging (DWI) in characterizing acute and chronic pathology after unilateral AKI in mice.
  
  
  METHODS
  Moderate or severe AKIs were induced in C57Bl/6 mice through transient unilateral clamping of the renal pedicle for 35 minutes (moderate AKI) or 45 minutes (severe AKI), respectively. Magnetic resonance imaging was performed in 10 animals with moderate AKI and 7 animals with severe AKI before surgery and at 5 time points thereafter (days 1, 7, 14, 21, 28) using a 7-T magnet. Fat-saturated T2-weighted images, multiecho turbo spin echo, and diffusion-weighed sequences (7 b values) were acquired in matching coronal planes. Parameter maps of T2 relaxation time and apparent diffusion coefficient (ADC) were calculated, and mean values were determined for the renal cortex, the outer medulla, and the inner medulla. Inflammatory cell infiltration with monocytes/macrophages (F4/80), T-lymphocytes (CD4, CD8), and dendritic cells (CD11c) as well as the degree of interstitial fibrosis 4 weeks after AKI were determined through renal histology and immunohistochemistry. Statistical analysis comprised unpaired t tests for group comparisons and correlation analysis between MRI parameters and kidney volume loss.
  
  
  RESULTS
  Increase of T2 relaxation time, indicating tissue edema, was most pronounced in the outer medulla and reached maximum values at d7 after AKI. At this time point, T2 values in the outer medulla were significantly increased to 53.8 ± 2.5 milliseconds after the severe AKI and to 46.3 ± 2.3 milliseconds after the moderate AKI when compared with the respective contralateral normal kidneys (40.9 ± 0.9 and 36.4 ± 1.2 milliseconds, respectively; P < 0.01). The T2 values reached baseline by d28. Medullary ADC was significantly reduced at all time points after AKI; restriction of diffusion was significantly more pronounced after the severe AKI than after the moderate AKI at d14 and d28. Changes of renal T2 and ADC values were associated with the severity of AKI as well as the degree of inflammatory cell infiltration and interstitial renal fibrosis 4 weeks after AKI. Furthermore, relative changes of both MRI parameters significantly correlated with kidney volume loss 4 weeks after AKI.
  
  
  CONCLUSIONS
  Measuring T2 and ADC values through MRI is a noninvasive way to determine the presence and severity of acute and chronic renal changes after AKI in mice. Thus, the method should prove useful in animal and human clinical studies.
authors.affiliation: From the *Institute for Diagnostic and Interventional Radiology, and †Department of Nephrology, Hannover Medical School, Hannover, Germany; ‡Laboratory of Organ Transplantation, Zunyi Medical College, Zunyi, China; §Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada; ∥Institute of Organ Transplantation, Tongji Hospital, Wuhan, China; and ¶Institute for Animal Science, Hannover Medical School, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Hueper
authors.forename: Song
authors.initials: S
authors.lastname: Rong
authors.forename: Marcel
authors.initials: M
authors.lastname: Gutberlet
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hartung
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Xia
authors.initials: X
authors.lastname: Lu
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Frank
authors.initials: F
authors.lastname: Wacker
authors.forename: Martin
authors.initials: M
authors.lastname: Meier
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000465:Algorithms; D000818:Animals; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007668:Kidney / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity