Rebeca Echeverria-Chasco1,2, Paloma L. Martin Moreno3, Nuria Garcia-Fernandez2,3, Marta Vidorreta4, Anne Oyarzun5, Arantxa Villanueva Larre2,5,6, Gorka Bastarrika1,2, and Maria A. Fernandez-Seara1,2
1Radiology, Clinica Universidad de Navarra, Pamplona, Spain, 2IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain, 3Nephrology, Clinica Universidad de Navarra, Pamplona, Spain, 4Siemens Healthcare, Madrid, Spain, 5Electrical Electronics and Communications Engineering, Public University of Navarre, Pamplona, Spain, 6ISC, Institute of Smart Cities, Pamplona, Spain
Synopsis
Purpose: to evaluate the prognostic potential of a
multiparametric renal MRI protocol (perfusion, diffusion and T1) for the
assessment of the allograft in the very early stages after transplantation.
Methods: 18 transplanted patients were imaged 6
days after the transplantation with ASL, IVIM and T1 mapping sequences. 2
groups were made depending on the allograft evolution (group A: no adverse
events and group B: any adverse event).
Results:
eGFR, album-creatinine ratio and cortical and medullary RBF were significantly
higher in allografts of group A than in group B. Significant correlations
between eGFR and RBF were found.
INTRODUCTION
The treatment of choice for patients
at end stage of chronic kidney disease is kidney transplantation. Monitoring renal function after transplantation is
essential to allow early detection of allograft impairment and thus, to
evaluate therapeutic strategies before an irreversible damage occurs.
In the clinical routine, evaluation of the allograft is
based on serum creatinine measurements, doppler ultrasonography and in some
cases renal biopsy. However, these methods have different limitations1,2. MRI has appeared as a promising noninvasive technique for
the assessment of functional and structural parameters of the allograft.
Arterial spin labeling (ASL)3 allows the quantification of renal perfusion without contrast
agents. Intravoxel Incoherent Motion (IVIM)4 provides information on microvascular perfusion and
diffusion in the tissue. Longitudinal relaxation times (T1 values) can be
indicative of alterations in tissue composition5.
Thus, the main goal of this work was to evaluate the
prognostic potential of a multiparametric renal MRI protocol (including
perfusion, diffusion and T1 measurements) for the assessment of the allograft
in the very early stages after transplantation.METHODS
SUBJECTS:
This study was approved by the local Ethics Committee. Written informed consent was
obtained from all subjects.
18 transplanted patients (mean age ± standard deviation (SD) =
56±13 years, 6 female)
were included . The interval between the renal surgery and the MR scan was 6±3 days.
Blood and urine samples were obtained from all patients
the day of the MR scan. Estimated glomerular filtration rate (eGFR) was
calculated according to Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equations based on creatinine6. None of the patients had any complication
during the surgery. All patients were followed for 3 months, monitoring any
adverse events (severe or moderate acute rejection, delayed graft function,
inflammation or infection).
According to the allograft evolution after transplantation,
subjects were divided into 2 groups: group A, recipients with no adverse events
(n=13) and group B, recipients that experienced any adverse event (n=5).
MRI PROTOCOL:
Scans were performed on a 3T Skyra (Siemens, Erlangen,
Germany) using an 18-channel body-array coil, without specific preparations,
such as fasting or fluid intake restrictions.
ASL: Pseudo-continuous ASL (PCASL) was
implemented as previously optimized7 with a SE-EPI readout, with background suppression. PCASL
was unbalanced with average gradient=0.5mT/m and ratio=6. RF pulses were
Hann-shaped (duration=500μs, period=1ms, B1=1.6µT). Labeling duration was 1.6s
and PLD was 1.2s. Sequence parameters are described in Table 1.
IVIM: Data was obtained for 13
b-values: 0,10, 20, 30, 40, 50, 70, 100, 200, 300, 400, 500, 800 s/mm2,
acquiring 3 signal averages with monopolar gradients in 3 orthogonal
directions. Single-shot EPI readout parameters are described in Table 1.
T1 mapping: An
Inversion Recovery sequence with a SE-EPI readout and 14 TIs was employed.
Readout parameters were identical to PCASL sequence (Table 1).
IMAGE PROCESSING:
Motion was corrected for each sequence and slice
using a PCA-groupwise registration method8 implemented in Elastix9. RBF maps in ml/min/100g were computed using
the single compartment model (Table 1). IVIM data was analyzed using a
biexponential decay model (Table 1), in which the second term describes pure
water diffusion, coefficient D (10-3mm2/s) and the first
term represents the fast molecule movement associated with microperfusion,
coefficient D∗ (10-3mm2/s) and Fp
(perfusion fraction) (%). T1 maps were calculated by fitting the signal to the
inversion-recovery equation (Table 1).
For each parameter map, tissue means
were calculated in manually defined masks in the cortex and medulla, drawn in
the M0 or b=0 images.
STATISTICAL ANALYSIS:
Differences between the groups were evaluated using a
Wilcoxon-Mann-Whitney test. Correlations between eGFR and imaging parameters
were assessed using Spearman correlation. P values<0.05 were considered
statistically significant. RESULTS
Figure 1 shows perfusion and diffusion parameter maps for
one subject in each group. In Figure 2 the parameter boxplots are illustrated
for the 2 groups in the renal cortex and medulla.
Table 2 shows cortical and
medullary parameters averaged for each group. eGFR, album-creatinine ratio and
cortical and medullary RBF were significantly higher in allografts of group A
than in group B.
Significant correlations between eGFR and RBF were found in
the cortex: r=0.68 (p<0.001) (Figure 3). However, eGFR did not correlate significantly
with the other imaging parameters. DISCUSSION AND CONCLUSSION
The results of this study suggest that perfusion measured in
the early post-operative period (one week after surgery) could be predictor of
allograft dysfunction during the initial months after transplantation.
RBF showed a good correlation with eGFR, demonstrating its
potential as a marker of renal function. In addition, a significant reduction
in renal perfusion was found in patients that presented adverse events in the
following months after the transplantation. RBF was low before these episodes
occur, being therefore a promising parameter with a predictive potential of
allograft dysfunction. Diffusion coefficients did not show statistically
significant differences between groups suggesting that the microstructure of the
kidney tissue was not altered in the early post-operative period.
Future work will include follow-up of these groups of
patients within a year after the transplantation.
In conclusion, RBF correlated significantly with allograft
function. Lower perfusion was found in patients that suffered an adverse event
in the following weeks after the transplantation, revealing its promising
clinical prognostic value.Acknowledgements
This project was supported by Government of Navarra, under
the frame of ERA PerMed (ERAPERMED2020-326 - RESPECT) and under the Grant:
PC181-182 RM-RENAL.
Rebeca Echeverria-Chasco received Ph.D. grant support from
Siemens Healthcare SpainReferences
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