Paul Kennedy1,2, Octavia Bane1,2, Sonja Gordic2,3, Stefanie Hectors1,2, Mark Berger1,2, Rafael Khaim4, Veronica Delaney4, Madhav Menon4, Fadi El Salem5, Sara Lewis1,2, and Bachir Taouli1,2
1Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States, 2Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States, 3University Hospital Zurich, Zurich, Switzerland, 4Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States, 5Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States
Synopsis
The aim of this study
is to determine whether MR and US elastography methods can differentiate
functional and chronically dysfunctional renal allografts by measuring renal
corticomedullary stiffness with MR elastography (MRE) and cortex stiffness with
ultrasound point shear wave elastography (pSWE). Our preliminary results
indicate that renal stiffness measured with MRE is significantly increased in
dysfunctional kidneys, while no significant difference was found with pSWE.
Renal stiffness measured with MRE also significantly correlated with Banff
scores for interstitial fibrosis and tubular atrophy. These preliminary results
suggest that MRE is sensitive to fibrotic changes in chronically
dysfunctional allografts.
Introduction
Early detection of renal
fibrosis in renal transplant recipients is important in order to tailor
treatment and ensure survival of the transplanted kidney. A mixture of biopsy,
urinalysis and blood markers is currently used to monitor renal transplant
health; however all have shortcomings such as invasiveness (for renal biopsy).
MR elastography (MRE) has been well established as a tool for staging liver
fibrosis and has recently been used to study renal transplants1-4.
The widespread availability of ultrasound (US) point shear wave elastography
(pSWE) has facilitated an increase in studies evaluating renal fibrosis5-7.
In this study, we compare the ability of MRE and pSWE methods to differentiate
stable functioning and chronically dysfunctional renal allografts.Methods
23 initial patients
were recruited into this IRB approved single center prospective study; 15 with
functional renal allografts (M/F 9/6 mean age 55.2±10.7 years, mean eGFR 65.9±12.6
ml/min/1.73m2) and 8 with chronic dysfunction and fibrosis (M/F 2/6,
mean age 53.6±12.5 years, mean eGFR 26.7±14.5 ml/min/1.73m2).
All dysfunctional and 4 stable function patients underwent biopsy within 1 year
of imaging. MRE was performed
on a 1.5T MR system (Aera, Siemens) in the coronal plane at 60Hz using a
modified 2D spin-echo EPI sequence with motion encoded in the through plane
direction, and a commercially available inversion algorithm8. pSWE was performed
immediately after MRE (S2000/S3000, Virtual Touch Quantification, Siemens) with
10 valid measurements obtained by one of 3 radiologists. Renal stiffness was
determined via magnitude of the complex shear modulus (MRE, |G*|) and Young’s
modulus (pSWE, E). MRE ROIs
were prescribed based on the automatically generated confidence map. pSWE exams
were considered valid if interquartile-range (IQR) was <30% of the median
value and success rate (percentage of successful measurements obtained) was
>60%. Elastography parameters were compared using the Mann-Whitney test.
Spearman correlations were calculated between elastography parameters and Banff
scores for interstitial fibrosis (ci), tubular atrophy (ct), vascular atrophy
(cv), tubulitis (t) and inflammation (i) in patients with biopsy. Results
MRE was successful in all patients,
while only 11/23 valid pSWE exams were obtained (Figure 1). |G*| was
significantly increased in chronically dysfunctional allografts compared to
stable function allografts (7.37±2.31 vs 5.50±1.52 kPa, p=0.034; Figure 2a). No significant difference in renal
stiffness was found between the groups when analyzing all pSWE exams (n=23,13.96±2.86
vs 13.03±5.07 kPa, p=0.44) or when including only valid pSWE measurements (n=11,
14.92±2.82 vs 13.47±2.52 kPa, p=0.37;
Figure 2b). In 12 patients with biopsy, |G*| was significantly correlated
with Banff parameters ct (r=0.628,
p=0.029) and ci (r=0.596, p=0.041). In the 8 patients with biopsy and valid pSWE
measurements, E significantly
correlated with cv (r=0.797, p=0.018). Neither |G*| or E were significantly correlated with
serum creatinine or eGFR. Preliminary ROC analysis showed |G*| to be the only
significant predictor of allograft dysfunction with an AUC of 0.812
(sensitivity 87.5%, specificity 57.1%, p=0.017).Discussion
These preliminary
results confirm recent findings showing an increase in renal stiffness of
fibrotic allografts using MRE2,3, with conflicting results also
reported1. None of our patients with chronically dysfunctional
allografts underwent dialysis, unlike the cohort studied by Marticorena et al1.
This may have affected allograft perfusion and contributed to reduced
stiffness. Our early results indicate that pSWE is unreliable for allograft
stiffness measurement. A potential cause for poor reliability is the
sensitivity of the measurement to transducer pressure9. The MRE data
presented here refer to corticomedullary stiffness due to the limited
measurable regions on 2D MRE confidence maps in renal allografts. This is a
limitation of 2D MRE which may be addressed with 3D MRE, as all three
directions of wave motion are included in the stiffness reconstruction. Conclusion
These initial results indicate
MRE is a more reliable and accurate method for non-invasive detection of
renal allograft dysfunction than pSWE. A future arm of this ongoing study will
incorporate shear wave elastography and 3D MRE to complement the pSWE and 2D
MRE methods used in the current study. Acknowledgements
This research was
supported by the National Institutes of Health NIDDK Grant 1F32DK109591,
Society of Abdominal Radiology (SAR) Morton Bosniak Research Award, and Guerbet
LLC Grant.References
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