Reliable Assessment of Swine Renal Fibrosis Using Quantitative Magnetization Transfer Imaging

Abstract

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 B 0 , B 1 , and T 1 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.

Evaluation of Renal Fibrosis Using Magnetization Transfer Imaging at 1.5T and 3T in a Porcine Model of Renal Artery Stenosis

“…To the best of our knowledge, this is the first study evaluating the reproducibility of MTI in ischemic kidneys as well as between 1.5T and 3T field strengths. Previous studies have demonstrated the feasibility of MTI in kidneys at 3T [19,[27][28][29]. In the present study, MTI showed good reproducibility at 3T, but we observed significant differences over time in the MTR values in the normal kidney cortex and medulla at 600 Hz and in the STK medulla at both 600 Hz and 1000 Hz.…”

The Proton Resonance Enhancement for CEST imaging and Shift Exchange (PRECISE) family of RF pulse shapes for Chemical Exchange Saturation Transfer MRI

“…The relaxation and semi-solid pool parameters were set based on previous studies on CEST and magnetization transfer contrast. [28][29][30][31] The parameters include: semi-solid pool concentration (𝑀 " $ ) = 1,554 mM, CEST concentration (𝑀 % $ ) = 50 mM, B0 field = 11.7 T (500 MHz), kba = 20 s -1 , kca = 500 -6,500 s -1 , T1a = 2 sec, T1b = 1 sec, T1c = 1 sec, T2a = 60 msec, T2b = 10 µsec, T2c =100 msec. We employed a 1 msec timestep for optimizing the 100 msec pulses (100 steps per 100 msec pulse) and a delay between of 1 to 100 msec between the pulses with a total of 2000 total steps for this pre-saturation pulse train including the pulses and delays.…”