Deep B. Gandhi1, Adebayo B. Braimah1, Jonathan Dudley1, Jean A. Tkach1, Amol Pednekar1, Andrew T. Trout1, Alexander G. Miethke2, Jeremiah A. Heilman3, Bogdan Dzyubak4, David S. Lake4, and Jonathan R. Dillman1
1Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2Division of Hepatology, Gastroenterology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 3Resoundant Inc., Rochester, MN, United States, 4Department of Radiology, Mayo Clinic, Rochester, MN, United States
Synopsis
Autoimmune
liver diseases lead to fibrosis and is manifested as excessive accumulation of extracellular
matrix and collagen that ultimately causes increase in liver stiffness. MR
Elastography (MRE) has proven to be an important tool to clinically diagnose
liver fibrosis. In this study we performed MRE at 1.5T on 65 subjects with
autoimmune liver disease. The data was then manually processed by 2 independent
readers and an automated algorithm. Near-perfect correlation and excellent
agreement were observed between Reader1 and Reader2 against the automated
algorithm (r=0.987 and r=0.981, respectively). Readers had excellent
inter-reader agreement(ICC=0.988) and the automated algorithm also
demonstrated perfect reproducibility.
INTRODUCTION
Autoimmune
liver diseases commonly lead to fibrosis (scarring), which is histopathologically
manifested as excessive accumulation of extracellular matrix and collagen[1,2].
This increase in tissue fibrosis leads to abnormally increased liver
stiffness over time[3]. Deposition of fibrosis can lead to liver
cirrhosis, portal hypertension, and ultimately liver failure and can warrant need
for liver transplantation in some individuals[2]. Liver biopsy has
been and continues to be the gold standard to diagnose and stage liver fibrosis;
however, it is invasive and has disadvantages such as pain to subjects due to its
invasive nature, sampling error, inter- and intra-pathologist variability, high
cost, and rare complications, such as internal bleeding that can result in prolonged
hospital stay[4]. Magnetic resonance elastography (MRE) has emerged
in recent years as a promising FDA-approved clinical tool to aid in non-invasively
diagnosing and staging liver fibrosis[5,6]. The goal of this study
is to compare liver shear stiffness estimates obtained by Automatic Liver Elasticity
Calculation (ALEC) processing of two-dimensional (2D) gradient-recalled echo
(GRE) MRE data to values obtained from standard-of-care manual processing.METHODS
Sixty-five
patients with autoimmune liver diseases (autoimmune/primary sclerosing
cholangitis (ASC/PSC) or autoimmune hepatitis (AIH) underwent 2D GRE MRE at 60
Hz on a 1.5T scanner (Ingenia; Philips Healthcare; Best, the Netherlands) as a
part of the imaging protocol for this IRB-approved study. The subjects were
instructed to lie down in supine position (head-first) on the scanner table,
with a passive pneumatic driver positioned on the upper right side of abdomen
over the liver to generate mechanical transverse waves at a set frequency and
amplitude. Imaging parameters for the clinical 2D GRE MRE sequence included: echo
time (TE) = 20.24 ms, time of repetition (TR) = 50 ms, slice thickness = 10 mm,
number of slices = 4, acquisition matrix = 252 x 80, flip angle = 20°, and field
of view (FOV) = 380 x 380 mm.
For
manual processing, elastograms were generated in Intellispace Portal v10.1
(Philips Healthcare) with two readers (R1, R2) independently placing
regions-of-interest (ROIs) to calculate mean liver stiffness weighted for ROI
size for all subjects (Figure 1, left). Care was taken to exclude blood
vessels and liver capsule, while staying within right lobe of the liver and
left medial segment. ALEC (Mayo Clinic; Rochester, MN) generated elastograms
with automatically segmented ROIs directly from MRE magnitude and phase images
for all subjects (Figure 1, right). Intellispace portal and ALEC both
used a Multimodal Direct Inversion (MMDI) algorithm for computation of
stiffness maps. Results obtained using manual and ALEC processing were then compared
using Pearson’s correlation (r), intra-class correlation coefficients (ICC),
and Bland-Altman analyses.RESULTS
Age of study participants ranged from 8 to 23
years (mean age: 15.5 years; 35 males). ICC for inter-reader agreement for
manual processing was excellent (ICC=0.988, 95%CI: 0.981-0.993), with mean bias
of 0.05 kPa (95% Limits of Agreement [LoA]: -0.46 to 0.56 kPa) (Figure 2). Correlation between manual and ALEC
processing was near-perfect (R1: r=0.986; R2: r=0.981; p-values <0.0001), with mean bias of -0.32 kPa (R1 95%
LoA: 0.36 to -1.00 kPa) and -0.28 kPa (R2 95% LoA: 0.41 to -0.98 kPa) (Figure
3, 4). ALEC measurements were perfectly reproducible (r=1, p<0.0001;
mean bias=0 kPa, 95% LoA: 0 kPa) (Figure 5). Manual processing on
average took 5:48 ± 1:07 minutes per subject. All the data was processed
automatically with ALEC in the background using batch file that took 3:30
minutes to set up. Mean computation time for each case using ALEC processing was
2:53 minutes on a Microsoft Windows 10 system with Intel® Core ™ i5-7500, 4
Core CPU, and 16 GB RAM.DISCUSSION AND CONCLUSION
Liver
stiffness values computed using ALEC showed excellent agreement with manual
analysis for both readers and were perfectly reproducible. Clinically, ALEC
processing of MRE data should eliminate inter-observer variability, facilitate
workflows, and reduce post processing time. Acknowledgements
Cincinnati Children's Hospital Medical Center - Center for Autoimmune Liver Disease fundingReferences
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