TY - JOUR
T1 - Reliable Assessment of Swine Renal Fibrosis Using Quantitative Magnetization Transfer Imaging
AU - Jiang, Kai
AU - Ferguson, Christopher M.
AU - Grimm, Roger C.
AU - Zhu, Xiangyang
AU - Glockner, James F.
AU - Lerman, Lilach O.
N1 - Funding Information:
Conflicts of interest and sources of funding: Lilach O. Lerman is an advisor to AstraZeneca, Butterfly Sciences, and Janssen Pharmaceuticals. No author has a relevant financial conflict of interest. This study was partly supported by National Institutes of Health grants DK122734, DK120292, and AG062104.
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Objectives Quantitative magnetization transfer (qMT) is useful for measurement of murine renal fibrosis at high and ultrahigh field strengths. However, its utility at clinical field strengths and in human-like kidneys remains unknown. We tested the hypothesis that qMT would successfully detect fibrosis in swine kidneys with unilateral renal artery stenosis (RAS) at 3.0 T. Methods The qMT protocol is composed of MT scans with variable flip angles and offset frequencies, and of B0, B1, and T1 mapping. Pigs were scanned 10 weeks after RAS or control. A 2-pool model was used to fit the bound pool fraction f of the renal cortex (CO) and outer medulla (OM). Then qMT-derived f in 5 normal and 10 RAS pigs was compared with histological fibrosis determined using Masson's trichrome staining and to renal perfusion assessed with computed tomography. Results The qMT 2-pool model provided accurate fittings of data collected on swine kidneys. Stenotic kidneys showed significantly elevated f in both the CO (9.8% ± 2.7% vs 6.4% ± 0.9%, P = 0.002) and OM (7.6% ± 2.2% vs 4.7% ± 1.1%, P = 0.002), as compared with normal kidneys. Histology-measured renal fibrosis and qMT-derived f correlated directly in both the cortex (Pearson correlation coefficient r = 0.93, P < 0.001) and OM (r = 0.84, P = 0.002), and inversely with stenotic kidney perfusion (r = 0.85, P = 0.002). Conclusions This study demonstrates the feasibility of qMT for measuring fibrosis in human-like swine kidneys, and the association between tissue macromolecule content and renal perfusion. Therefore, qMT may be useful as a tool for noninvasive assessment of renal fibrosis in subjects with RAS at clinical field strengths.
AB - Objectives Quantitative magnetization transfer (qMT) is useful for measurement of murine renal fibrosis at high and ultrahigh field strengths. However, its utility at clinical field strengths and in human-like kidneys remains unknown. We tested the hypothesis that qMT would successfully detect fibrosis in swine kidneys with unilateral renal artery stenosis (RAS) at 3.0 T. Methods The qMT protocol is composed of MT scans with variable flip angles and offset frequencies, and of B0, B1, and T1 mapping. Pigs were scanned 10 weeks after RAS or control. A 2-pool model was used to fit the bound pool fraction f of the renal cortex (CO) and outer medulla (OM). Then qMT-derived f in 5 normal and 10 RAS pigs was compared with histological fibrosis determined using Masson's trichrome staining and to renal perfusion assessed with computed tomography. Results The qMT 2-pool model provided accurate fittings of data collected on swine kidneys. Stenotic kidneys showed significantly elevated f in both the CO (9.8% ± 2.7% vs 6.4% ± 0.9%, P = 0.002) and OM (7.6% ± 2.2% vs 4.7% ± 1.1%, P = 0.002), as compared with normal kidneys. Histology-measured renal fibrosis and qMT-derived f correlated directly in both the cortex (Pearson correlation coefficient r = 0.93, P < 0.001) and OM (r = 0.84, P = 0.002), and inversely with stenotic kidney perfusion (r = 0.85, P = 0.002). Conclusions This study demonstrates the feasibility of qMT for measuring fibrosis in human-like swine kidneys, and the association between tissue macromolecule content and renal perfusion. Therefore, qMT may be useful as a tool for noninvasive assessment of renal fibrosis in subjects with RAS at clinical field strengths.
KW - quantitative magnetization transfer
KW - renal artery stenosis
KW - renal fibrosis
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U2 - 10.1097/RLI.0000000000000843
DO - 10.1097/RLI.0000000000000843
M3 - Article
C2 - 34935650
AN - SCOPUS:85128245980
SN - 0020-9996
VL - 57
SP - 334
EP - 342
JO - Investigative Radiology
JF - Investigative Radiology
IS - 5
ER -