Octavia Bane1,2, Sara Lewis1,2, Stefanie Hectors1,2, Sonja Gordic2,3, Paul Kennedy1,2, Mathilde Wagner2,4, Michael Markl5,6, Rafael Khaim7, Veronica Delaney7, Fadi El Salem8, Madhav Menon7, 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, 4Groupe Hospitalier Pitie-Salpetriere, Paris, France, 5Feinberg School of Medicine, Radiology, Northwestern University, Chicago, IL, United States, 6McCormick School of Engineering, Biomedical Engineering, Northwestern University, Chicago, IL, United States, 7Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States, 8Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States
Synopsis
In this preliminary study, we sought to determine the
test-retest repeatability of flow quantification in renal allograft vessels
using a 4D flow phase-contrast (PC) MRI sequence, and to correlate flow
parameters with renal function. We observed significantly decreased renal
arterial flow in allografts with chronic dysfunction, as well as positive
correlation between flow and velocities in renal transplant vessels and renal
function. We conclude that 4D flow imaging is sensitive to the vascular changes
that accompany renal transplant dysfunction, to be confirmed in a larger study.
Introduction
Phase-contrast MRI is a
promising method for flow quantification of renal transplant vessels, as it
does not employ gadolinium-based contrast agents, but has been poorly reported.
The goals of our study are to report our preliminary experience with 4D flow in
renal transplants, determine the test-retest repeatability of flow quantification
in renal allograft vessels using a 4D flow phase-contrast (PC) MRI sequence,
and to correlate flow parameters with eGFR. Methods
21 initial
patients including 12 with functional renal allografts (M/F 6/6 mean age 54y,
estimated MDRD serum eGFR 66±11 ml/min/1.73m2, range 50-87
ml/min/1.73m2), 9 with chronic dysfunction (M/F, 4/5, mean age 53.6
y, eGFR 27±15 ml/min/1.73m2,
range 12-63
ml/min/1.73 m2) were enrolled in this IRB-approved single center
prospective study. All patients had Cartesian 4D flow imaging at 1.5T (Aera,
Siemens), as part of a multiparametric MRI protocol, which included dynamic contrast-enhanced
MRI (DCE-MRI) in patients without renal dysfunction. Three patients (2 with
functional allografts, 1 with chronic dysfunction without biopsy-proven
fibrosis) underwent re-test imaging on a second visit 18±9
days after the first.
The 4D flow acquisition
consisted of a coronal-oblique abdominal 60 mm slab (TR/TE/FA 62.4/2.9/9º, FOV
400x400 mm, acquired matrix size 160 x 160 x12, acquired voxel size 2.5 x 2.5 x
5 mm3, interpolated voxel size 1.3 x 1.3 x 2.5 mm3, temporal
resolution 66-71 ms), covering the renal allograft in the pelvis. 4D flow was
acquired for 3 minutes during free breathing, with a velocity encoding
parameter (VENC) of 120 cm/sec.
Images were analyzed using prototype
software (Siemens Healthcare) by 2 observers in consensus. After performing
corrections for phase aliasing, eddy currents and motion, vessels surrounding
the allograft, including the main stems of the renal artery (RA) and renal vein
(RV) (Fig. 1), as well as the right
(RILA) and left common iliac artery (LILA)
were identified and segmented. Time-averaged vessel cross-section area,
through-plane velocity and flow, as well as maximum velocity, were measured. Agreement
on vessel identification between the test-retest sessions was evaluated by
Cohen’s kappa. Test-retest agreement of area, average and peak velocity and
flow measurements was evaluated by coefficient of variation (CV) and
Bland-Altman statistics. Flow parameters for the segmented vessels, as well as
for the iliac artery ipsilateral to the allograft (right/left iliac fossa allograft
placement: 17/4 allografts) were compared between patients with functional and dysfunctional
allografts by Mann-Whitney tests. Flow parameters were correlated to serum eGFR
by Spearman correlation. Results
Table 1 shows test-retest statistics for individual vessels.
There was excellent agreement between test-retest sessions in segmenting the
vessels (Cohen’s kappa=1, p=0.046). Area, velocity and flow measurements showed
acceptable to low test-retest agreement, with CV and bias <35%, but high
limits of agreement.
There was significantly
decreased RA flow (p=0.005) in patients with allograft dysfunction (Table 2). There were trends towards
significant decrease of RV area and flow, and trend towards decreased
ipsilateral iliac artery (ILA) velocity and flow (Table 2). There were significant moderate positive correlations
between each of RA flow (Spearman’s ρ=0.544, p=0.018) and ILA flow (Spearman’s ρ=0.457,
p=0.0039) with eGFR. We observed AUC of 0.875 (p=0.006), sensitivity of 87.5%
and specificity of 90.9% (using cut-off value for RA flow of 6.5 ml/s) for
diagnosing allograft dysfunction.
Discussion
The maximum velocities measured in the RA in our
study are in agreement with a recent study performed in renal allograft
recipients1. Test-retest agreement was modest in this initial
study with 3 patients undergoing re-test visits almost 20 days apart. The
modest agreement may be due to physiologic variation in hemodynamic state. We
did not observe significant differences in the RV in this preliminary study,
since our acquisition parameters (VENC= 120 cm/sec) were more
sensitive to arterial flow. Data acquired with acquisition parameters sensitive
to venous flow (VENC= 45 cm/sec) is forthcoming.
Factors that restrict RA
flow, such as renal artery stenosis, may affect renal function and blood
pressure regulation after transplantation2. The development of fibrosis with decreased renal
artery flow has been shown in animal models of renal artery stenosis3. Our study shows that 4D flow can potentially be used
as a non-contrast method to diagnose renal dysfunction.
Conclusion
4D flow imaging is sensitive to the vascular changes
that accompany chronic renal dysfunction, with the causal relationship between
vascular flow and renal dysfunction to be investigated in a larger mechanistic
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
1. Motoyama
D, Ishii Y, Takehara Y, et al. Four-dimensional phase-contrast vastly
undersampled isotropic projection reconstruction (4D PC-VIPR) MR evaluation of
the renal arteries in transplant recipients: Preliminary results. Journal of
magnetic resonance imaging : JMRI 2017;46(2):595-603.
2. Sankari
BR, Geisinger M, Zelch M, Brouhard B, Cunningham R, Novick AC. Post-transplant
renal artery stenosis: impact of therapy on long-term kidney function and blood
pressure control. The Journal of urology 1996;155(6):1860-1864.
3. Korsmo
MJ, Ebrahimi B, Eirin A, et al. Magnetic resonance elastography noninvasively
detects in vivo renal medullary fibrosis secondary to swine renal artery
stenosis. Investigative radiology 2013;48(2):61-68.