title: Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis.
abstract: Purpose To test the utility of magnetization transfer imaging in detecting and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis. Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. Renal artery stenosis surgery (n = 10) or sham surgery (n = 5) was performed, and the stenotic and contralateral kidneys were studied longitudinally in vivo at baseline and 2, 4, and 6 weeks after surgery. After a 16.4-T magnetic resonance imaging examination, magnetization transfer ratio was measured as an index of fibrosis (guided by parameters selected in preliminary phantom studies). In addition, renal volume, perfusion, blood flow, and oxygenation were assessed. Fibrosis was subsequently measured ex vivo by means of histologic analysis and hydroxyproline assay. The Wilcoxon rank sum or signed rank test was used for statistical comparisons between or within groups, and Pearson and Spearman rank correlation was used to compare fibrosis measured in vivo and ex vivo. Results In the stenotic kidney, the median magnetization transfer ratio showed progressive increases from baseline to 6 weeks after surgery (increases of 13.7% [P = .0006] and 21.3% [P = .0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week magnetization transfer ratio map showed good correlation with fibrosis measured ex vivo (Pearson r = 0.9038 and Spearman ρ = 0.8107 [P = .0002 vs trichrome staining]; r = 0.9540 and ρ = 0.8821 [P < .0001 vs Sirius red staining]; and r = 0.8429 and ρ = 0.7607 [P = .001 vs hydroxyproline assay]). Conclusion Magnetization transfer imaging was used successfully to measure and longitudinally monitor the progression of renal fibrosis in mice with unilateral renal artery stenosis.©RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ferguson
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Kline
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Burningham
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Prassana K
authors.initials: PK
authors.lastname: Mishra
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Slobodan I
authors.initials: SI
authors.lastname: Macura
authors.affiliation: From the Division of Nephrology and Hypertension (K.J., C.M.F., B.E., H.T., T.A.B., L.O.L.), Department of Radiology (T.L.K.), Department of Biochemistry and Molecular Biology (P.K.M., S.I.M.), and Department of Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D005355:Fibrosis; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D011446:Prospective Studies; D012078:Renal Artery Obstruction / Q000000981:diagnostic imaging* / Q000473:pathology*; D015203:Reproducibility of Results