Juan Pablo Meneses1,2, Juan Cristobal Gana3, Jose Eduardo Galgani4,5, Cristian Tejos1,2,6, Zhaolin Chen7,8, and Sergio Uribe1,2,9
1Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, Chile, 2i-Health Millennium Institute for Intelligent Healthcare Engineering, Santiago, Chile, 3Pediatric Gastroenterology and Nutrition Department, Division of Pediatrics, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile, 4Nutrition & Dietetics. Department of Health Sciences; Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile, 5Department of Nutrition, Diabetes and Metabolism. Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile, 6Department of Electrical Engineering, Pontificia Universidad Catolica de Chile, Santiago, Chile, 7Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia, 8Department of Data Science and AI, Monash University, Melbourne, VIC, Australia, 9Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, VIC, Australia
Synopsis
Keywords: Other AI/ML, Machine Learning/Artificial Intelligence, Generative Model
Motivation: Deep Learning (DL)-based methods to quantify liver PDFF have had robustness difficulties due to the lack of large and heterogeneous training datasets with known results.
Goal(s): To create a DL algorithm to synthesize realistic multi-echo liver MR images given a set of arbitrary MR scan parameters.
Approach: To use a physics-driven approach to create a DL-based generative model able to synthesize realistic liver CSE-MR images with different compositions and geometries.
Results: Our framework enabled a reliable customization of MR scan parameters, by directly adjusting them in the physical model. Feasibility of training a DL method purely based on synthetic data was also demonstrated.
Impact: We successfully
generated realistic multi-echo liver MR images with diverse geometries and
compositions, which can be used to efficiently train DL-based methods for liver
PDFF quantification. The physics-driven nature of our model enables the customization
of MR scan parameters.
Introduction
MRI
Proton Density Fat Fraction (PDFF) is a biomarker that is highly correlated to Metabolic
dysfunction-Associated Fatty Liver Disease (MAFLD)1,2. In recent studies, numerous Deep
Learning (DL)-based PDFF quantification methods have been proposed to
accelerate the required scan times and post-processing stages. However, they
have not achieved an optimal robustness to different MR scanners or scan
protocols3, mainly due to cost and time limitations associated to the gathering
of a heterogeneous enough dataset.
To address
this issue, we propose a physics-based generative model to artificially
synthesize multi-echo Chemical Shift-Encoded (CSE) liver MR images, which correspond
to the required data to calculate water and fat compositions.Theory
The CSE-MR signal at the n-th echo (In), at echo-time TEn, is defined as a function of the water and fat
proton densities (ρW, ρF), the R2* signal decay, and the
off-resonance field (ϕ):
$$I_n=e^{-R_2^*\cdot TE_n}\cdot e^{i2\pi\phi^*\cdot TE_n}\cdot [\rho_W+\rho_F\sum_p\alpha_p\cdot e^{i2\pi f_p\cdot TE_n}]$$
where an a
priori known 6-peak fat signal spectrum is considered (fp and αp are each peak's frequency and relative amplitude, respectively)4. If the MR signal is separated into water-only
and fat-only components, then the PDFF corresponds to the ratio ρF / (ρW + ρF).Methods
We propose a Physics-Informed Variational Auto-Encoder (PI-VAE), an attention-based convolutional neural network with an encoder-multi-decoder
architecture whose outputs are the variables involved in the MR signal model (ρW, ρF, R2*, ϕ), whilst the input are series of multi-echo
liver CSE-MR images (Figure 1).
Specifically, PI-VAE is composed of three decoders to separately estimate water-only
images, fat-only images, and the parametric maps R2* and ϕ, which are merged into a single complex-valued
field-map: ξ=ϕ+iR2*/2π.
PI-VAE was trained using multi-slice CSE-MR
scans from 172 subjects (3842 axial slices) with heterogeneous levels of
hepatic PDFF (Figure 2).
The chosen loss function measured: 1) the perceptual similarity between
original and reconstructed liver MRI ($$$\mathcal{L}_P$$$),
2) the numerical error between reference and reconstructed water/fat images
(same for R2* and ϕ) ($$$\mathcal{L}_S$$$),
and 3) an adversarial loss that assessed the realism of the generated MR images
($$$\mathcal{L}_D$$$):
$$\mathcal{L}=\alpha_P\cdot\mathcal{L}_P+\alpha_S\cdot\mathcal{L}_S+\alpha_D\cdot\mathcal{L}_D+\alpha_{KL}\cdot\mathcal{L}_{KL}$$
The
latent space was regularized to achieve a zero-centered and low-variance
feature space ($$$\mathcal{L}_{KL}$$$), which enables the posterior generation from
latent space features that are randomly sampled from a standard normal
distribution. Then, since the decoders can generate ρW, ρF,
R2*, ϕ
from the sampled latent space, our framework enables the generation of liver
CSE-MR images with customizable echo-times and field-strengths (by varying the fat
spectrum).Results
As showed in Figure 3,
PI-VAE can generate realistic liver water-fat images and parametric maps (R2*, ϕ)
with random geometries, and
multi-echo MR images at customized echo times.
Compared
to a validation dataset (384 slices, unobserved during training), a randomly
synthesized dataset showed a similar distribution. Distribution similarity metrics
such as Fréchet Inception Distance (FID) and Maximum Mean Discrepancy (MMD) were
9.65% and 0.46%, respectively. Both scores measure the distance between two different
distributions, and therefore values closer to zero indicate a greater
similarity. Moreover, single and Multi-Scale (MS) Structural Similarity Index
Measure (SSIM) scores between pairs of synthetic samples also showed an
acceptable variability (SSIM = 78.72%; MS-SSIM = 56.37%), as shown in Figure 4.
Finally,
we also trained a previously proposed DL-based method for PDFF quantification5 only using synthetic data, and we
compared it to the original version trained using a data-augmentation workflow.
Considering measurements at two ROIs on a liver CSE-MRI testing dataset with
different echo-times, we observed a bias of 0.81±2.57% and -0.41±0.88% for synthetic-data
and original versions, respectively. Reference values were obtained using
iterative Graph Cuts6. Nevertheless, reproducibility
coefficients (RDC) of 1.78±1.00 and 6.96±13.64% for synthetic-data and original
versions, respectively, showed a precision diminishing.Discussion
PI-VAE
can synthesize realistic liver CSE-MR images with various geometries, along
with their water/fat compositions. Unlike previously proposed generative models
for similar medical imaging applications, PI-VAE allows an easy and reliable
adjustment of the scanning parameters by incorporating the signal generation
physics into the generation process.
Moreover,
due to the reduced dimensionality of the latent space, the generative process
is highly efficient in terms of computational cost. This represents a great
opportunity to train DL-based methods using data synthesized with PI-VAE, since
the generation could be performed during training by randomly sampling latent
spaces and decoding them at each iteration.Conclusion
The
generation of realistic and diverse liver CSE-MR images using our PI-VAE can be
useful to address the lack of large datasets to train DL methods. PI-VAE may
also be extended to artificially synthesize other MR modalities related to an
analytical physical model (i.e.: MR relaxometry, QSM, etc.).Acknowledgements
This
work was funded by Fondecyt 1200839. J.M. was funded by the National Agency for
Research and Development (ANID) / Scholarship Program / DOCTORADO BECAS
CHILE/2020 – 21210665. CT was funded by Fondecyt 1231535 and Millennium Institute for Intelligent Healthcare
Engineering, iHEALTH (ICN2021_004).References
1. Eslam, M. et al. A new
definition for metabolic dysfunction-associated fatty liver disease: An
international expert consensus statement. J Hepatol 73, 202–209
(2020).
2. Idilman, I. S. et al. Hepatic
steatosis: Quantification by proton density fat fraction with MR imaging
versus liver biopsy. Radiology 267, 767–775 (2013).
3. Daudé, P. et al. Comparative
review of algorithms and methods for chemical‐shift‐encoded quantitative fat‐water
imaging. Magn Reson Med (2023) doi:10.1002/mrm.29860.
4. Hamilton, G. et al. In vivo
characterization of the liver fat 1H MR spectrum. NMR Biomed 24,
784–790 (2011).
5. Meneses, J. P. et al.
Reproducible DL-based approach for liver PDFF quantification. in ISMRM
Annual Meeting (2023).
6. Hernando, D., Kellman, P., Haldar, J.
P. & Liang, Z. P. Robust water/fat separation in the presence of large
field inhomogeneities using a graph cut algorithm. Magn Reson Med 63, 79–90
(2010).