Perfusion and T₂ Relaxation Time as Predictors of Severity and Outcome in Sepsis‐Associated Acute Kidney Injury: A Preclinical MRI Study

Abstract

BackgroundPreventing sepsis‐associated acute kidney injury (S‐AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow‐up and outcome are important to intervene and prevent further damage.PurposeTo establish a noninvasive multiparametric MRI (mpMRI) tool, including T1, T2, and perfusion mapping, for probability assessment of the outcome of S‐AKI.Study TypePreclinical randomized prospective study.Animal ModelOne hundred and forty adult female SD rats (65 control and 75 sepsis).Field Strength/Sequence9.4T; T1 and perfusion map (FAIR‐EPI) and T2 map (multiecho RARE).AssessmentExperiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1, T2, perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow‐up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours.Statistical TestsMann–Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant.ResultsSeverely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 μmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52).Data ConclusionThis preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning.Level of Evidence2Technical Efficacy Stage2

In vivo monitoring of renal tubule volume fraction using dynamic parametric MRI

“…These components can be separated using a two‐order exponential decay as follows: $$$$ \mathrm{I}\left(\mathrm{t}\right)={{\mathrm{A}}_1}^{\ast}\exp\ \left(-\mathrm{t}/{T}_{2\_ long}\right)+{{\mathrm{A}}_2}^{\ast}\exp\ \left(-\mathrm{t}/{T}_{2\_ short}\right) $$$$ where I(t) is the signal amplitude; t is the evolution time used for T 2 weighting; T 2_ long and T 2 _short are the T 2 relaxation times of the long and short components; and A 1 and A 2 are the initial signal amplitudes of the long and short components. Typical values of T 2 for the renal tissue layers of healthy rats at 9.4 T are 90.0–68.5 ms in the inner medulla (IM), 50.0–43.0 ms in the outer medulla (OM), and 43.0–36.6 ms in the cortex (CO) 20,21 . Therefore, we considered a relaxation time range of 10–100 ms for T 2_short to represent renal parenchyma and blood.…”

“…Gaussian-distributed white noise was applied to the signal, such that SNR = mean(s)/σ is similar to the noise typically found in the magnitude images from in vivo studies. A dictionary of simulated T 2 decay curves was acquired by repeating the simulations with different T 2_short = [5,10,15,20,25,30,35,40,45,50,60, 70, 85, 100 ms], T 2_long = 500 ms, T 1_short = 1820 ms, T 1_long = 3400 ms, refocusing flip angle = (122…”

“…[17][18][19] Because the parenchyma and blood compartments exhibit a similar T 2 , and only the tubular fluid has a considerably longer T 2 relaxation, the T 2 decay curves can be approximated with a bi-exponential decay. Zhao et al reported a T 2 of approximately 41 ms for the renal cortex and T 2 of approximately 52 ms for the outer medulla 20,21 ; for arterial blood, a T 2 of about 40 ms was reported by Lee et al 22 If the T 2 decay is sampled at appropriate time points, the contributions of slow and fast T 2 relaxation components can be separated with bi-exponential modeling to provide useful information on the renal microstructure. 23,24 This study aims to evaluate T 2 mapping as a tool to noninvasively probe renal tissue properties in vivo as a potential marker for early diagnosis of kidney diseases.…”

Editorial for “Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis‐Associated Acute Kidney Injury: A Preclinical MRI Study”

“…7 In this issue of JMRI, Zhao et al combine relaxation measurements (T 1 , T 2 ) and perfusion (ASL) into a multimodal MRI protocol to investigate S-AKI. 8 Two parallel experiments were conducted using a rat model of peritoneal contamination and infection in comparison with healthy control animals. In the first experiment, severity of AKI as determined by serum creatinine was compared with histological changes in the kidneys over the first 24 hours after induction of sepsis.…”

“…Combined with the results from Liu et al, this would suggest the need for future research focusing on more extended temporal sampling of the animals ideally with serial MRI scanning. 7,8 Such an approach may also help capture changes that characterize the progression from AKI to CKD.…”