Lei Jiang1, Paul Territo1, Brian McCarthy1, Amanda A. Riley1, Sourajit Mustafi1, Yu-Chien Wu1, Bruce Molitoris2, Gary Hutchins1, and Chen Lin1
1Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, 2Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
Synopsis
The objective of this study is to evaluate the capability of
quantitative MRI techniques to measure physiological changes associated with changes
in renal function in a rat model. Our investigation suggest that the results of
T2* mapping, intra-voxel incoherent motion (IVIM), and T1ρ imaging are
comparable to the published results. These techniques can be used to assess and
monitor different aspects of physiological changes in kidney fibrosis.Purpose
The objective of this study is to evaluate the sensitivity of three quantitative
MRI techniques to measure physiological changes associated with renal fibrosis
in a rat model. We investigated T2* blood oxygenation level-dependent imaging
(T
2* BOLD) for renal tissue oxygenation [2], T1ρ imaging for macromolecular composition [3], and
intra-voxel incoherent motion (IVIM) imaging for pseudo perfusion (
Df)
and perfusion fraction (
Pf) [4].
Methods
The investigation was conducted following the Institutional Animal Care
and Use Committee (IACUC) guidelines. Four rats were studied following a unilateral
Ischemia-Reperfusion (I/R) intervention. Fibrosis in one of the kidneys was
introduced by clamping the pedicle (Artery, Vein and Pelvis) for 50min. Subsequent MRI examinations were performed on
a Siemens Tim Trio 3T scanner using an 80mm inner diameter
8-channel rat body coil (RAPID MRI, Germany). Rats were
anaesthetized with 2-4% isoflurane (balance medical oxygen) through a dedicated
nose cone. The MR imaging protocol included a coronal T2-weighted
3D SPACE sequence (FOV=150mm, Resolution=0.5 x 0.5 x 0.5mm
3)
for anatomical imaging as well as transverse multi-echo GRE sequence for T2*(10
TEs of 8 - 66ms), T1ρ
prepared 3D spoiled GRE sequence for T1ρ (9 spin-lock (SL) times of 5 - 80ms) and diffusion
weighted (DW) single-shot EPI sequence for IVIM (10 b-values of 0-750s/mm
2).
These transverse images have matching slices of FOV 80 x 80mm
2,
matrix 192 x 192 and 2mm slice thickness.
All rats were scanned at early (2-5 days) and late (25-35 days) time
points after the surgical intervention. Two types of ROI were drawn: one that covers
both the cortex and medulla in each kidney and another one in the paraspinal muscle
area. The results from muscle ROI serve as an internal reference in the
longitudinal study. Quantitative
T1ρ maps (Figure2) are created by fitting the signal intensity of T1ρ-weighted MR images
as a function of the SL pulse duration with fixed amplitude. T
2* maps (Figure2) are
obtained by fitting the signal intensities as a function of TE times. In
addition, Df and Pf are computed by bi-exponential fitting the change
of MRI signal with b-values using the Levenberg-Marquardt algorithm. Statistical t-test analyses
were conducted and p< 0.05 was considered statistically significant.
Results
T2w 3D SPACE Images (Figure 1) shows the typical anatomical
images of the injured (left side) and healthy (right side) rat kidneys. The injured
kidney atropied after more than one month and its apperance in T
2 weighted images
changed compared to the healthy kidney, demonstrating the progression of
fibrosis. As shown in Table 1 , the T
2* values were similar in both healthy and
injured kidneys at early time points , whereas significantly decreased T2*
values were observed in injured kidney at
late time points (p = 0.017). Table 1 also shows significant differences in
IVIM Df and Pf values. It appears that the IVIM for injured
kidney at early time points is significantly different from healthy kidney (p=0.0122 for Df and 0.0022 for Pf, respectively) and late stage (p=0.044 for Df
and 0.0002 for Pf, respectively).
However, although we could detect T1ρ increase in the injured kidney, compared to
the healthy kidney between the early and late stages, there was no significant
difference between healthy vs injured (p=0.8414/0.3734) and early vs late
(p=0.1625) for T1p. For the muscle ROIs, there was always no significant
difference between early vs. late time points for all three imaging studies.
Discussion
In this limited pilot study we demonstrated the feasibility of
performing high quality quantitative functional imaging in the rat kidney using
dedicated imaging coils and advanced imaging techniques originally developed
for human applications. The results
obtained in this study demonstrate statistically significant changes in
multiple MRI derived measures of tissue physiology (T
2*, Df, Pf) at both early
and late time points following an ischemia/reperfusion intervention. However, we did not observe any significant
differences in the data generated using the T1p method. These
preliminary results suggest that multiple MRI derived parameters have the
potential to provide important information about changes in kidney function
shortly after an initial insult and during the progression of kidney disease
and increasing levels of fibrotic burden. The sample size of this study was very small and further studies are
warranted to confirm these initial observations and establish the utility of
MRI derived parameters as biomarkers of kidney disease and disease progression
over time.
Conclusions
These findings suggest that the results of IVIM, T
2*, and T1p
are comparable to the published results[2-4]. Further investigations are needed
to improve the T1p method. These techniques may be useful for monitoring
changes in kidney physiology associated with kidney disease or injury.
Acknowledgements
No acknowledgement found.References
1. Inoue T, et al. Noninvasive evaluation of
kidney hypoxia and fibrosis using magnetic resonance imaging. J Am Soc Nephrol.
2011 Aug;22(8):1429-34.
2. Li LP, et al. Evaluation of intrarenal
oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats
by blood oxygen level-dependent magnetic resonance imaging. Invest Radiol. 2014
Jun;49(6):403-10
3. Wang YX, et al. T1rho MR imaging is sensitive
to evaluate liver fibrosis: an experimental study in a rat biliary duct
ligation model. Radiology. 2011 Jun;259(3):712-9
4. Wu HH, et al. Monitoring the progression of
renal fibrosis by T2-weighted signal intensity and diffusion weighted magnetic
resonance imaging in cisplatin induced rat models. Chin Med J (Engl). 2015 Mar
5;128(5):626-31