Utsav Shrestha1, Cara Morin2,3, Ralf Loeffler4, Zachary R. Abramson2, Jane Hankins2, Claudia Hillenbrand4, and Aaryani Tipirneni-Sajja1,2
1The University of Memphis, Memphis, TN, United States, 2St. Jude Children's Research Hospital, Memphis, TN, United States, 3Cincinnati Children’s Hospital Medical Center, CINCINNATI, OH, United States, 4University of New South Wales, Sydney, Australia
Synopsis
Keywords: Liver, Liver, Deep Learning, Vessel Segmentation, R2*, HIC
Ultra-short echo time (UTE) imaging increases the
accuracy of R2*-based hepatic iron content (HIC) quantification in cases of
high iron overload when conventional GRE sequences can fail due to rapid signal
decay. Segmenting whole liver to estimate liver R2* requires human expert and is
time consuming. In this study, we trained a convolutional neural network (CNN)
to automatically segment the liver parenchyma on radial UTE acquisitions using
magnitude images and R2* maps. Our results show an excellent agreement between manual and CNN-based liver
segmentation and mean R2* values, hence demonstrating the potential of our
proposed method for automated HIC assessment.
Introduction
Quantification
of hepatic iron content (HIC) using R2*-MRI is an alternative to liver biopsy.
Multi-echo gradient echo (GRE) sequences are typically used to measure
R2*-based HIC, however, they can produce inaccurate R2* values or fail at high
iron overload conditions (HIC >15 mg Fe/g) due to rapid signal decay before
the shortest possible TE ~1.0 ms.1 Alternatively, ultra-short echo time
(UTE) imaging with TEs as short as 0.1 ms has been reported to increase the
accuracy of R2* quantification in cases of high iron overload.2 Another benefit of UTE is that it is
based on radial sampling making it robust to motion, and thus, can be performed
under free breathing (FB).2,3 Mean liver R2* values are estimated by
manually drawing region-of-interest (ROI) either on a small homogenous area of
liver without vessels4,5 or the whole liver and excluding
vessels using postprocessing.3,5,6 Although the whole liver ROI reduces the inter-reviewer
variability,6 both methods still require a trained
expert and are time consuming. The objective of this study is to automate the
segmentation of whole liver parenchyma on FB UTE acquisitions using convolutional
neural network (CNN) for improving the workflow and accuracy of R2*-based HIC
reporting for clinical diagnosis and treatment of iron overload.Materials and Methods
One
hundred forty-three 2D multi-echo UTE datasets were collected retrospectively
from patients with suspected iron overload.7 The liver was manually segmented by
drawing a whole liver ROI encompassing the entire liver on the 2D
cross-sectional image and is used as the ground truth mask. R2* maps were
calculated using a monoexponential model with noise subtraction.2,7 A two-dimensional U-Net CNN8 was trained for liver segmentation
independently on both magnitude images (mag-U-Net) and R2*-maps (R2*-U-Net).
All magnitude TE images were used as an independent input to the CNN because
they had different image contrasts. The images had dimension of 192x192 and
were normalized to (0-1) range. Data augmentation using rotation (±30°), zoom
(±0.1) and shear (±15°) was applied for the training process.
The U-Net architecture consisted of five
up-sampling and down-sampling layers with kernel size of three and number of
filters between up-sampling layers was increased by 2n. Batch
normalization and dropout was applied after each layer. Training was performed
using 10-fold cross-validation with early stopping and reduce learning rate
(LR) on plateau with minimum LR of 0.0000001 callbacks for 300 epochs (batch
size=64) using ADAM optimizer, initial LR=0.01 and combined loss function of
dice-coefficient and binary cross-entropy. Transfer learning was applied on
mag-U-Net to train on R2*maps with the same CNN parameters. After liver
segmentation, Frangi filter was applied to remove vessels,5 and the mean R2* was calculated for the
extracted liver parenchyma and was converted to HIC using published R2*-HIC
calibration.9 One-way ANOVA was performed to compare the accuracy of the
extracted liver areas and the mean R2* values between the two U-net techniques
and the ground truth, with p<0.05 considered to be statistically significant.Results and discussion
Representative
images of the extracted parenchyma obtained using U-Nets trained on magnitude
images and R2* maps along with their corresponding ground truth segmentation
are shown in Fig. 1. The mean validation dice-score for magnitude and R2* based
U-Net segmentations for the entire cohort were 0.98±0.02 and 0.92±0.12,
respectively. Figure 2 shows that the extracted R2* maps and mean R2*/HIC
values obtained with both U-Nets for mild, moderate and high iron overload
cases were very similar and in close agreement with those obtained for
ground-truth. For the entire cohort, the extracted liver area and the mean
estimated R2* values using mag-U-Net and R2*-U-Net masks were not significantly
different from the ground truth results for both before and after vessel
segmentation (Table 1). The extracted liver areas and mean R2*/HIC values for
both the U-Nets demonstrated excellent correlation (r>0.98) to ground truth
segmentation with a mean bias close to zero and narrow limits of agreement.
(Fig. 3, Fig. 4).
Different deep learning techniques
have been reported for segmenting liver parenchyma using Cartesian GRE
acquisitions for automated R2* estimation,10,11 however, none of them were evaluated
yet for radial UTE acquisition. Our study shows the feasibility of using U-Net
to segment the whole liver and extract mean R2* values with high accuracy using
both magnitude images at different TEs and only R2* maps using transfer
learning. Some limitations are this study was performed on single slice 2D UTE
data collected from a single center and a single scanner. Future work includes
training and testing CNN liver segmentation and mean R2* estimation on 3D UTE
and multi-center and multi-vendor data. Conclusion
Our results show an excellent agreement between manual and
U-Net based liver segmentation, hence demonstrating the accuracy and robustness
of the CNN for automated parenchyma extraction and estimation of whole liver
R2*. This automated technique can substantially improve radiologist workflow
while reducing bias and inter-rater variability in the assessment of hepatic
iron content, an important clinical parameter guiding iron removal therapy.Acknowledgements
No acknowledgement found.References
1. Wood
JC, Enriquez C, Ghugre N, et al. MRI R2 and R2* mapping accurately estimates
hepatic iron concentration in transfusion-dependent thalassemia and sickle cell
disease patients. Blood. 2005;106(4):1460-1465.
2. Krafft
AJ, Loeffler RB, Song R, et al. Quantitative ultrashort echo time imaging for
assessment of massive iron overload at 1.5 and 3 Tesla. Magnetic resonance in medicine. 2017;78(5):1839-1851.
3. Tipirneni-Sajja
A, Krafft AJ, McCarville MB, et al. Radial ultrashort TE imaging removes the
need for breath-holding in hepatic iron overload quantification by R2* MRI. AJR American journal of roentgenology. 2017;209(1):187.
4. Schwenzer
NF, Machann J, Haap MM, et al. T2* relaxometry in liver, pancreas, and spleen
in a healthy cohort of one hundred twenty-nine subjects–correlation with age,
gender, and serum ferritin. Investigative
radiology. 2008;43(12):854-860.
5. Tipirneni‐Sajja
A, Song R, McCarville MB, Loeffler RB, Hankins JS, Hillenbrand CM. Automated
vessel exclusion technique for quantitative assessment of hepatic iron overload
by‐MRI. Journal of Magnetic Resonance
Imaging. 2018;47(6):1542-1551.
6. McCarville
MB, Hillenbrand CM, Loeffler RB, et al. Comparison of whole liver and small
region-of-interest measurements of MRI liver R2* in children with iron
overload. Pediatric radiology. 2010;40(8):1360-1367.
7. Tipirneni‐Sajja
A, Loeffler RB, Krafft AJ, et al. Ultrashort echo time imaging for
quantification of hepatic iron overload: Comparison of acquisition and fitting
methods via simulations, phantoms, and in vivo data. Journal of Magnetic Resonance Imaging. 2019;49(5):1475-1488.
8. Ronneberger
O, Fischer P, Brox T. U-net: Convolutional networks for biomedical image
segmentation. Paper presented at: International Conference on Medical image
computing and computer-assisted intervention2015.
9. Hankins
JS, McCarville MB, Loeffler RB, et al. R2* magnetic resonance imaging of the
liver in patients with iron overload. Blood,
The Journal of the American Society of Hematology. 2009;113(20):4853-4855.
10. Loeffler
RB, McCarville MB, Tipirneni-Sajja A, Hankins JS, Hillenbrand CM. Automated MR
HIC determination using deep learning and Frangi filters. Paper presented at:
Proceedings of the 28th annual meeting of ISMRM2020.
11. Liu M, Vanguri R, Mutasa S, et al.
Channel width optimized neural networks for liver and vessel segmentation in
liver iron quantification. Computers in
Biology and Medicine. 2020;122:103798.