Imaging fibrosis in pediatric kidney transplantation: A pilot study.

2023

e14540

05/2023

1399-3046

BACKGROUND: Noninvasive alternatives to biopsy for assessment of interstitial fibrosis and tubular atrophy (IFTA), the major determinant of kidney transplant failure, remain profoundly limited. Elastography is a noninvasive technique that propagates shear waves across tissues to measure their stiffness. We aimed to test utility of elastography for early detection of IFTA in pediatric kidney allografts.

METHODS: We compared ultrasound (USE) and MR elastography (MRE) stiffness measurements, performed on pediatric transplant recipients referred for clinically indicated biopsies, and healthy controls.

RESULTS: Ten transplant recipients (median age 16 years) and eight controls (median age 16.5 years) were enrolled. Three transplant recipients had "stable" allografts and seven had Banff Grade 1 IFTA. Median time from transplantation to biopsy was 12 months. Mean estimated glomerular filtration rate was 61.5 mL/min/1.73m by creatinine-cystatin-C CKiD equation at time of biopsy. Mean stiffness, calculated through one-way ANOVA, was higher for IFTA allografts (23.4 kPa USE/5.6 kPa MRE) than stable allografts (13.7 kPa USE/4.4 kPa MRE) and controls (9.1 kPa USE/3.6 kPa MRE). Pearson's coefficient between USE and MRE stiffness values was strong (r = .97). AUC for fibrosis prediction in transplanted kidneys was high for both modalities (0.91 USE and 0.89 MRE), although statistically nonsignificant (p > .05). Stiffness cut-off values for USE and MRE were 13.8 kPa and 4.6 kPa, respectively. Both values yielded a sensitivity of 100% but USE specificity (72%) was slightly higher than MRE (67%).

CONCLUSION: Elastography shows potential for detection of low-grade IFTA in allografts although a larger sample is imperative for clinical validation.

10.1111/petr.14540

Pediatr Transplant

37166372

Liver and spleen volume and stiffness in patients post-Fontan procedure and patients with ARPKD compared to normal controls.

2022

147-154

07/2022

1873-4499

PURPOSE: Both congestive (patients post-Fontan hepatopathy) and congenital (patients with ARPKD) disease can lead to hepatic fibrosis and portal hypertension with eventual development of splenomegaly. We investigated liver and spleen stiffness as measured by MRE between post-Fontan, ARPKD patients and controls independent of organ volume.

METHODS: Our study included 122 subjects (70 Fontan patients, 14 ARPKD patients, and 38 controls). The mean MRE liver and spleen stiffness values of Fontan patients and patients with ARPKD were compared to controls. Similarly, the liver and spleen volumes of the Fontan patients and patients with ARPKD were then compared to the volumes of controls.

RESULTS: Post-Fontan and ARPKD patients, mean liver stiffness, mean liver volume as well as mean spleen stiffness and mean spleen volume were higher than mean liver stiffness, mean liver volume, mean spleen stiffness, and mean spleen volume of controls. While liver stiffness correlated to liver volume in controls, we found no correlation between stiffness and volume in either Fontan or ARPKD patients, which indicates MRE's ability to act as an independent biomarker. However, these findings are not true in the spleen, where there is significant association between volume and stiffness in patients with ARPKD, but not in Fontan patients or controls.

CONCLUSION: Liver and spleen stiffness and volumes are significantly different among Fontan patients, ARPKD patients, and controls. Our findings suggest that beyond diagnosing fibrosis, MRE cut-off values could be disease-specific since not only the severity but the underlying pathology causing organ congestion or fibrosis influences MRE results.

10.1016/j.clinimag.2022.06.022

Clin Imaging

35835018

Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

2021

157-162

2021 01

1530-0447

<p><strong>BACKGROUND: </strong>Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.</p>

<p><strong>METHODS: </strong>In this study, animal and human magnetic resonance imaging (MRI) scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild-type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.</p>

<p><strong>RESULTS: </strong>Mean kidney T1 and T2 relaxation times showed significant increases with age (p &lt; 0.05) as well as significant increases in comparison to WT mice (p &lt; 2 × 10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p = 0.030) and T2 (p = 0.054) as a function of total kidney volume, respectively. Initial magnetic resonance fingerprinting assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.</p>

<p><strong>CONCLUSIONS: </strong>These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.</p>

<p><strong>IMPACT: </strong>A major roadblock for implementing clinical trials in patients with ARPKD is the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. A clinical need exists to develop a safe and sensitive measure for kidney disease progression, and eventually therapeutic efficacy, for patients with ARPKD. Mean kidney T1 and T2 MRI relaxation times showed significant increases with age (p &lt; 0.05) as well as significant increases in comparison to WT mice (p &lt; 2 ×10), indicating that T1 and T2 may provide sensitive assessments of cystic changes associated with progressive ARPKD kidney disease. This preclinical and initial clinical study suggests that MRI-based kidney T1 and T2 mapping could be used as a non-invasive assessment of ARPKD kidney disease progression. These non-invasive, quantitative MRI techniques could eventually be used as an outcome measure for clinical trials evaluating novel therapeutics aimed at limiting or preventing ARPKD kidney disease progression.</p>

10.1038/s41390-020-0883-9

Pediatr Res

32283547

Feasibility of T2 Mapping of the Sacroiliac Joints in Healthy Control Subjects and Children and Young Adults with Sacroiliitis.

2021

2021 Nov 10

2578-5745

<p><strong>OBJECTIVE: </strong>To assess the feasibility of T2 mapping for evaluating pediatric SIJ cartilage at 3 Tesla (T) magnetic resonance imaging (MRI).</p>

<p><strong>METHODS: </strong>Healthy control subjects and adolescents with sacroiliitis underwent a 3T MRI dedicated pelvic protocol that included a T2 mapping sequence consisting of multislice, multiecho acquisition. Healthy control subjects were prospectively recruited from our primary care practices as part of a larger imaging study, whereas adolescents with sacroiliitis were recruited specifically for this study. Regions of interest (ROIs) were hand-drawn by a senior pediatric radiologist twice and a radiology fellow twice to calibrate and test reliability using the intraclass correlation coefficient (ICC). T2 relaxation time between control subjects and cases was compared using univariate linear regression. We tested the association of T2 relaxation time in adolescents with sacroiliitis with patient-reported outcomes and the Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) inflammation and structural scores using Pearson correlation coefficients.</p>

<p><strong>RESULTS: </strong>Fourteen subjects were evaluable (six control subjects: median age 13.7 years [interquartile range (IQR): 12.2-15.5], 67% male patients; eight cases: median age 17.4 years [IQR: 12.5-20], 88% male patients]. Acquisition time for T2 mapping sequences was approximately 6 minutes, and segmenting the ROI for each SIJ took approximately 3 minutes. The intrarater and inter-rater ICCs were 0.67 and 0.46, respectively, indicating good to fair reliability. There was a trend, albeit statistically insignificant, in longer median T2 relaxation time in cases (43.04 ms; IQR: 41.25-49.76 ms) versus healthy control subjects (40.0 ms; IQR: 38.9-48.6 ms). Although not statistically significant, cases with longer T2 relaxation time tended to occur with poorer patient-reported outcomes. Correlations with the SIJ inflammation and structural lesion scores were weak.</p>

<p><strong>CONCLUSION: </strong>T2 mapping of the SIJ cartilage in children was feasible and reliable. Larger controlled and longitudinal assessments are needed to assess the validity and utility of these measurements for routine clinical practice and trials.</p>

10.1002/acr2.11354

ACR Open Rheumatol

34757697

Two-dimensional (2D) morphologic measurements can quantify the severity of liver disease in children with autosomal recessive polycystic kidney disease (ARPKD).

2021

2021 Jun 26

2366-0058

<p><strong>PURPOSE: </strong>To evaluate the correlation of 2D shape-based features with magnetic resonance elastography (MRE)-derived liver stiffness and portal hypertension (pHTN) in children with ARPKD-associated congenital hepatic fibrosis.</p>

<p><strong>METHODS: </strong>In a prospective IRB-approved study, 14 children with ARPKD (mean age ± SD = 13.8 ± 5.8&nbsp;years) and 14 healthy controls (mean age ± SD = 13.7 ± 3.9&nbsp;years) underwent liver MRE. A 2D region of interest (ROI) outlining the left liver lobe at the level of the abdominal aorta was drawn on sagittal T2-weighted images. Eight shape features (perimeter, major axis length, maximum diameter, perimeter to surface ratio (PSR), elongation, sphericity, minor axis length, and mesh surface) describing the 2D-ROI were calculated. Spearman's correlation was calculated between shape features and MRE-derived liver stiffness (kPa) (n = 28). Shape features were compared between participants with ARPKD with pHTN (splenomegaly and thrombocytopenia), (n = 4) and without pHTN (n = 8) using the Mann Whitney U test. Receiver operating characteristic (ROC) curves were generated to examine the diagnostic accuracy of shape features in identifying cases with liver stiffness &gt; 2.9&nbsp;kPa.</p>

<p><strong>RESULTS: </strong>In ARPKD participants and healthy controls, all eight shape features, except elongation, showed moderate to strong correlation with liver stiffness (kPa); the perimeter surface ratio had the strongest correlation (rho = - 0.75, p &lt; 0.001). In ROC analysis, a cut-off of PSR ≤ 0.057&nbsp;mm gave 100% (95% CI: 59.0-100.0) sensitivity and 100% (95% CI: 83.9-100.0) specificity in identifying ARPKD participants with liver stiffness &gt; 2.9&nbsp;kPa, with an area under the ROC curve (AUC) of 1.0 (95% CI: 0.88-1.00). Individuals with pHTN had a lower median PSR (mean ± SD = 0.05 ± 0.01) than those without (0.07 ± 0.01; p = 0.027) with an AUC of 0.91 (95% CI: 0.60-0.99) in differentiating the participants with and without pHTN.</p>

<p><strong>CONCLUSION: </strong>Shape-based features of the left liver lobe show potential as non-invasive biomarkers of liver fibrosis and portal hypertension in children with ARPKD.</p>

10.1007/s00261-021-03189-3

Abdom Radiol (NY)

34173844

Magnetic resonance elastography to quantify liver disease severity in autosomal recessive polycystic kidney disease.

2020

2020 Aug 05

2366-0058

<p><strong>OBJECTIVES: </strong>To evaluate whether liver and spleen magnetic resonance elastography (MRE) can measure the severity of congenital hepatic fibrosis (CHF) and portal hypertension (pHTN) in individuals with autosomal recessive polycystic kidney disease (ARPKD), and to examine correlations between liver MRE and ultrasound (US) elastography.</p>

<p><strong>METHODS: </strong>Cross-sectional study of nine individuals with ARPKD and 14 healthy controls. MRE was performed to measure mean liver and spleen stiffness (kPa); US elastography was performed to measure point shear wave speed (SWS) in both liver lobes. We compared: (1) MRE liver and spleen stiffness between controls vs. ARPKD; and (2) MRE liver stiffness between participants with ARPKD without vs. with pHTN, and examined correlations between MRE liver stiffness, spleen length, platelet counts, and US elastography SWS. Receiver operating characteristic (ROC) analysis was performed to examine diagnostic accuracy of liver MRE.</p>

<p><strong>RESULTS: </strong>Participants with ARPKD (median age 16.8 [IQR 13.3, 18.9] years) had higher median MRE liver stiffness than controls (median age 14.7 [IQR 9.7, 16.7&nbsp;years) (2.55 vs. 1.92&nbsp;kPa, p = 0.008), but MRE spleen stiffness did not differ. ARPKD participants with pHTN had higher median MRE liver stiffness than those without (3.60&nbsp;kPa vs 2.49&nbsp;kPa, p = 0.05). Liver MRE and US elastography measurements were strongly correlated. To distinguish ARPKD vs. control groups, liver MRE had 78% sensitivity and 93% specificity at a proposed cut-off of 2.48&nbsp;kPa [ROC area 0.83 (95% CI 0.63-1.00)].</p>

<p><strong>CONCLUSION: </strong>Liver MRE may be a useful quantitative method to measure the severity of CHF and pHTN in individuals with ARPKD.</p>

10.1007/s00261-020-02694-1

Abdom Radiol (NY)

32757071

Magnetic resonance elastography SE-EPI vs GRE sequences at 3T in a pediatric population with liver disease.

2019

894-902

2019 03

2366-0058

<p><strong>PURPOSE: </strong>The goal of our study is to compare hepatic stiffness measures using gradient-recalled echo (GRE) versus spin-echo echo planar imaging (SE-EPI)-based MR Elastography (MRE) at 3T used to measure hepatic stiffness in a patients with suspected liver diseases.</p>

<p><strong>MATERIALS AND METHODS: </strong>This retrospective study included 52 patients with liver disease who underwent a 3T MRE exam including both an investigational SE-EPI-based technique and a product GRE-based technique. Regions of interest (ROI) were placed on the elastograms to measure elastography-derived liver stiffness as well as the area included within the ROIs. The mean liver stiffness values and area of ROIs were compared.</p>

<p><strong>RESULTS: </strong>The mean liver stiffness was 3.72 kilopascal (kPa) ± 1.29 using GRE MRE and 3.78&nbsp;kPa ± 1.13 using SE-EPI MRE. Measurement of liver stiffness showed excellent agreement between the two pulse sequences with a mean bias of - 0.1&nbsp;kPa (range - 1.8 to 1.7&nbsp;kPa) between sequences. The mean measurable ROI area was higher with SE-EPI (313.8&nbsp;cm ± 213.8) than with the GRE technique (208.6&nbsp;cm ± 114.8), and the difference was statistically significant (P &lt; 0.05).</p>

<p><strong>CONCLUSIONS: </strong>Our data shows excellent agreement of measured liver stiffness between GRE and SE-EPI-based sequences at 3T. Our results show the advantage of a SE-EPI MRE sequence in terms of image quality, ROI size and acquisition time with equivalent liver stiffness measurements as compared to GRE-MRE sequence.</p>

10.1007/s00261-018-1884-6

Abdom Radiol (NY)

30600386

Specific Absorption Rate and Specific Energy Dose: Comparison of 1.5-T versus 3.0-T Fetal MRI.

2020

191550

2020 Apr 07

1527-1315

<p><strong>Background</strong> MRI performed at 3.0 T offers greater signal-to-noise ratio and better spatial resolution than does MRI performed at 1.5 T; however, for fetal MRI, there are concerns about the potential for greater radiofrequency energy administered to the fetus at 3.0-T MRI. <strong>Purpose</strong> To compare the specific absorption rate (SAR) and specific energy dose (SED) of fetal MRI at 1.5 and 3.0 T. <strong>Materials and Methods</strong> In this retrospective study, all fetal MRI examinations performed with 1.5- and 3.0-T scanners at one institution between July 2012 and October 2016 were evaluated. Two-dimensional (2D) and three-dimensional (3D) steady-state free precession (SSFP), single-shot fast spin-echo, 2D and 3D T1-weighted spoiled gradient-echo (SPGR), and echo-planar imaging sequences were performed. SAR, SED, accumulated SED, and acquisition time were retrieved from the Digital Imaging and Communications in Medicine header. Data are presented as mean ± standard deviation. Two one-sided tests with equivalence bounds of 0.5 (Cohen effect size) were performed, with statistical equivalence considered at &lt; .05. <strong>Results</strong> A total of 2952 pregnant women were evaluated. Mean maternal age was 30 years ± 6 (age range, 12-49 years), mean gestational age was 24 weeks ± 6 (range, 17-40 weeks). A total of 3247 fetal MRI scans were included, with 2784 (86%) obtained at 1.5 T and 463 (14%) obtained at 3.0 T. In total, 93 764 sequences were performed, with 81 535 (87%) performed at 1.5 T and 12 229 (13%) performed at 3.0 T. When comparing 1.5- with 3.0-T MRI sequences, mean SAR (1.09 W/kg ± 0.69 vs 1.14 W/kg ± 0.61), mean SED (33 J/kg ± 27 vs 38 J/kg ± 26), and mean accumulated SED (965 J/kg ± 408 vs 996 J/kg ± 366, &lt; .001) were equivalent. <strong>Conclusion</strong> Fetal 1.5- and 3.0-T MRI examinations were found to have equivalent energy metrics in most cases. The 3.0-T sequences, such as two-dimensional T1-weighted spoiled gradient-echo and three-dimensional steady-state free precession, may require modification to keep the energy delivered to the patient as low as possible. © RSNA, 2020</p>

10.1148/radiol.2020191550

Radiology

32255418

DTI of the kidney in children: comparison between normal kidneys and those with ureteropelvic junction (UPJ) obstruction.

2019

2019 Dec 16

1352-8661

<p><strong>OBJECTIVE: </strong>To compare renal diffusion tensor imaging (DTI) parameters in patients with or without ureteropelvic junction (UPJ) obstruction.</p>

<p><strong>METHODS: </strong>Patients that underwent functional MR urography (MRU) with renal DTI were retrospectively selected. Kidneys deemed normal on T2-weighted images and functional parameters were used as controls and compared to those kidneys with morphologic and functional findings of UPJ obstruction. DTI included a 20-direction DTI with b values of b = 0&nbsp;s/mm and b = 400&nbsp;s/mm. Diffusion Toolkit was used for analysis and segmentation. TrackVis was used to draw regions of interest (ROI) covering the entire volume of the renal parenchyma, excluding the collecting system. Fibers were reconstructed using a deterministic fiber tracking algorithm. Whole kidney ROI-based analysis was performed to obtain cortico-medullary measurements (FA, ADC and track length) for each kidney. T tests were performed to compare means and statistical significance was defined at p &lt; 0.05.</p>

<p><strong>RESULTS: </strong>118 normal kidneys from 102 patients (median age 7&nbsp;years, IQR 6-15&nbsp;years; 58 males and 44 females) were compared to 22 kidneys from 16 patients (median age 13&nbsp;years, IQR 3-15&nbsp;years; 9 males and 7 females) with UPJ obstruction. Mean FA values were significantly lower (0.31 ± 0.07; n = 22) in kidneys with UPJ obstruction than normal kidneys (0.40 ± 0.08; n = 118) (p &lt; 0.001). ADC was marginally significantly increased (p = 0.01) and track length was not significantly different (p = 0.24).</p>

<p><strong>CONCLUSION: </strong>Our results suggest that DTI-derived metrics including FA and ADC are potential biomarkers to differentiate kidneys with UPJ obstruction and assess renal parenchymal damage.</p>

10.1007/s10334-019-00812-9

MAGMA

31845301

R2 relaxometry based MR imaging for estimation of liver iron content: A comparison between two methods.

2019

2019 Jun 03

2366-0058

<p><strong>PURPOSE: </strong>To compare the reproducibility and accuracy of R2-relaxometry MRI for estimation&nbsp;of liver iron concentration (LIC) between in-house analysis and FDA-approved commercially available third party results.</p>

<p><strong>METHODS: </strong>All MR studies were performed on a 1.5T scanner.&nbsp;Multi-echo spin-echo scans with a fixed TR and increasing TE values of 6&nbsp;ms, 9&nbsp;ms, 12&nbsp;ms, 15&nbsp;ms, and 18&nbsp;ms (spaced at 3&nbsp;ms intervals) were used. Post-processing of the images to calculate mean relaxivity, R2, included drawing of regions of interest to include the whole liver on mid-slice. The relationship between liver R2 values and estimated LIC calculated with in-house analysis and values&nbsp;reported by an external company (FerriScan, Resonance Health, Australia) were assessed with correlation coefficients and Bland-Altman difference plots. Continuous variables are presented as mean ± standard deviation. Significance was set at p value &lt; 0.05.</p>

<p><strong>RESULTS: </strong>474 studies from 175 patients were included in the study (mean age 10.4 ± 4.2&nbsp;years (range 1-18&nbsp;years); 254 studies from girls, 220 studies from boys). LIC ranged from 0.6 to 43&nbsp;mg/g dry tissue, covering a broad range from normal levels to extremely high iron levels. Linearity between proprietary and in-house methods was excellent across the observed range for R2 (31.5 to 334.8&nbsp;s); showing a correlation coefficient of r = 0.87, p &lt; 0.001. Bland-Altman R2 difference plot between the two methods shows a mean bias of + 21.5&nbsp;s (range - 47.0 to + 90.0&nbsp;s between two standard deviations). LIC reported by FerriScan compared with LIC estimated in-house with R2 as reported by FerriScan agreed strongly, (r = 1.0, p &lt; 0.001).</p>

<p><strong>CONCLUSION: </strong>R2 relaxometry MR imaging for liver iron concentration estimation is reproducible between proprietary FDA-approved commercial software and in-house analysis methods.</p>

10.1007/s00261-019-02074-4

Abdom Radiol (NY)

31161282