Thomas Campbell Arnold1, Serhat V Okar2, Danni Tu3, Govind Nair2, John T. Pitts4, Megan E. Poorman4, Karan D. Kawatra2, Lisa M. Desiderio5, Matthew K. Schindler6, Brian Litt6, Russell T. Shinohara3, Daniel S. Reich2, and Joel M. Stein5
1Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 2National Institute of Neurological Disorders and Stroke, Bethesda, MD, United States, 3Biostatistics, University of Pennsylvania, Philadelphia, PA, United States, 4Hyperfine, Guilford, CT, United States, 5Radiology, University of Pennsylvania, Philadelphia, PA, United States, 6Neurology, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Keywords: Machine Learning/Artificial Intelligence, Low-Field MRI, super resolution
High-field
MRI provides superior imaging for diverse clinical applications, but cost and
other factors limit availability in various healthcare and lower resource
settings. Lower-field strength units promise to expand access but involve
tradeoffs including reduced signal, longer scan times, and lower resolution.
Here we develop super-resolution methods that can generate high-field quality images
from low-field scanner inputs, thus increasing signal and resolution. We use
generative adversarial networks to demonstrate image enhancement in T1, T2 and
FLAIR sequences.
Introduction
Recently, there has been renewed academic and
commercial interest in lower-field strength scanners.1 While low-field
scanners have shown promise in a variety of clinical applications,2–4 obtaining
diagnostic quality sequences on these lower magnetic field strength devices requires careful
balancing of scan parameters.5 In order to maintain clinically
relevant acquisition times, low-field sequences often have reduced signal and lower
resolution. Generative adversarial networks (GANs) have emerged as a powerful
deep-learning-based technique that have been applied to a variety of image
enhancement problems.6 Here, we apply GANs to a dataset of
same-day, paired high-field and low-field imaging to enhance the image quality
of low-field images.Methods
2.1 Dataset
To develop the super-resolution algorithms, we used a
dataset of 36 head MRIs obtained from patients with multiple sclerosis at two
academic hospitals. Each patient underwent whole-brain imaging on 3T scanners
(Siemens, Erlangen, Germany) with 3D T1-weighted (T1w), T2-weighted (T2w), and
3D T2-FLAIR sequences, though sequence parameters varied between sites. Each
patient underwent same-day whole-brain low-field imaging using a 64mT portable scanner
(Hyperfine, Guilford, CT) with 3D fast spin-echo T1w, T2w, and T2-FLAIR scans
in the axial plane. Low-field protocols were identical between sites. Each
patient in the dataset was subsequently randomized to a training (N=24),
validation (N=6), or test (N=6) set for machine learning model development.
2.2 Preprocessing
All scans were first resliced to 1mm isotropic
resolution. Paired high-field imaging was then coregistered to low-field
imaging using a dense rigid registration with Advanced Normalization Tools
(ANTs). Each 3D acquisition was normalized to a 0 to 255 range, padded to
square in the axial plane, and output as a series of jpg files. To encode some
3D information into the 2D jpg files, we incorporated adjacent slices into the
3 RGB channels of each jpg file (Figure 1). This 2.5D approach permits the
model to access information about neighboring slices which can result in
reduced image artifacts and improved continuity between slices. For each
sagittal slice (K) in the dataset, the additional 2 RGB channels were filled
with values from K+2 and K-2 slices (i.e. 2 mm distance from the central
slice).
2.3 Model training
To enhance the low-field images, we employed the
pix2pix paired Generative Adversarial Network (GAN) with PyTorch backend (https://github.com/junyanz/pytorch-CycleGAN-and-pix2pix).7 This model
consists of a generator (Unet-256) and a discriminator (70x70 patchGAN). Models
were trained for 100 epochs using a learning rate of 2e-4 with linear decay
after 30 epochs and a batch size of 32. Training data were augmented using
random horizontal flipping.
2.4 Model evaluation and statistics
Model performance was assessed on the held-out test
set (N=6) using three quantitative metrics: mean squared error (MSE),
structural similarity index measure (SSIM), and peak signal-to-noise ratio
(PSNR). For each quantitative metric, we used subject-level paired t-tests to
compare the low-field and super-resolution enhanced imaging. All statistics
were generated using scipy (v1.7.3), numpy (v1.21.6), and seaborn (v0.12.1) in
Python (v3.7.5).Results
Model performance was assessed on the test set (N=6)
using the three quantitative metrics: MSE, SSIM, and PSNR. For reference, we also
applied these quantitative metrics to the non-enhanced low-field data. The
models for T1 and T2 enhancement showed a significant improvement in MSE (T1: p
= 0.048, T2: p = 0.022) and PSNR (T1: p = 0.01, T2: p = 0.019), though no
effect was found for SSIM. The FLAIR model demonstrated SSIM improvement (p =
0.004), but no effect was seen for MSE and PSNR. Table 1 lists summary
statistics and statistical comparisons for each metric. Figures 2-4 illustrate model
performance for FLAIR, T1, and T2 sequences respectively.Discussion
In this project, we developed a GAN that takes low-field
scans as input and attempts to generate high-field quality images as output.
While this initial effort demonstrates promise in a limited context, there are
a number of limitations to the model as it has been developed and there are
significant opportunities for further model improvement. First, we utilized a
limited dataset containing only axial head images. While our approach was
sufficient within this limited dataset, it is unlikely to generalize to new
scanners and anatomical structures. More aggressive data augmentation
techniques could be one potential route to increase the robustness of the
model. Additionally, there was some degree of discontinuity in pixel
intensities between adjacent slices. While we employed a 2.5D approach to
mitigate image artifacts and slice-to-slice discontinuity, it was limited to
only 3 channels. In future work, additional slices and sequences could be
encoded in additional channels. More advanced registration methods may also
decrease differences between high-field and low-field datasets. Finally, augmenting
the loss function to incorporate quantitative metrics may provide more relevant
feedback to the model and further improve the perceived quality of the
simulated images.Acknowledgements
Acknowledgements
We thank current and former team members
at Hyperfine, Inc. (Guilford, CT), particularly Jonathan Rothberg, PhD,
Samantha By, PhD, and Edward B. Welch, PhD, for technical assistance and the
use of Hyperfine low-field MRI scanners. We thank the Penn Neuroradiology Research
Core, including Brian Dolan, Marisa Sanchez, Leeanne Lezotte, Danielle Urban, and Lauren Karpf,
for assistance with patient recruitment and scanning. We also acknowledge the
staff of the NINDS Neuroimmunology Clinic; Rose Cuento, CRNP;
and the staff of the NIH NMR Center.
Funding
T. Campbell Arnold was funded in part by
the HHMI-NIBIB Interfaces Initiative (5T32EB009384-10). Additional support was
provided by NINDS (DP1-NS122038, R56-NS099348, T32-NS091006) (BL), the
Pennsylvania Health Research Formula Fund (BL), the Mirowski Family Fund (BL),
the Jonathan Rothberg Family Fund (BL), and Neil and Barbara Smit (BL). This
study received support from a research services agreement between Hyperfine,
Inc. and the Trustees of the University of Pennsylvania (JMS). The study was
partially funded by the Intramural Research Program of NINDS/NIH (DSR).
Disclosures
Sehat Okar, Karan
Kawatra, and Govind Nair are supported by the Intramural Research Program of
NINDS. John Pitts and Megan Poorman are employees of Hyperfine. Brian Litt is a
co-founder of Liminal Science and serves on the Medical and Scientific Advisory
Boards or Hyperfine and as a result has equity in the company. Russell T.
Shinohara receives consulting income from Octave Bioscience, compensation for
reviewing scientific articles from the American Medical Association and for
reviewing grants for the Emerson Collective, National Institutes of Health, and
the Department of Defense. Daniel S. Reich is supported by the Intramural
Research Program of NINDS and additional research support from Abata and Sanofi-Genzyme. Joel M. Stein has received
support from sponsored research agreements with Hyperfine and consulting income
from Centaur Diagnostics, Inc.
References
1. Arnold TC, Freeman CW, Litt
B, Stein JM. Low‐field MRI: Clinical promise and challenges. J Magn Reson
Imaging. Published online September 19, 2022. doi:10.1002/jmri.28408
2. Sheth KN, Mazurek MH, Yuen
MM, et al. Assessment of Brain Injury Using Portable, Low-Field Magnetic
Resonance Imaging at the Bedside of Critically Ill Patients. JAMA Neurol.
Published online September 8, 2020. doi:10.1001/jamaneurol.2020.3263
3. Arnold TC, Tu D, Okar S V.,
et al. Sensitivity of portable low-field magnetic resonance imaging for
multiple sclerosis lesions. NeuroImage Clin. 2022;35:103101.
doi:10.1016/j.nicl.2022.103101
4. Deoni SCL, Bruchhage MMK,
Beauchemin J, et al. Accessible pediatric neuroimaging using a low field
strength MRI scanner. Neuroimage. 2021;238:118273. doi:10.1016/j.neuroimage.2021.118273
5. Marques JP, Simonis FFJ,
Webb AG. Low‐field MRI: An MR physics perspective. J Magn Reson Imaging.
2019;49(6):1528-1542. doi:10.1002/jmri.26637
6. Yi X, Walia E, Babyn P.
Generative adversarial network in medical imaging: A review. Med Image Anal.
2019;58:101552. doi:10.1016/J.MEDIA.2019.101552
7. Zhu
J-Y, Park T, Isola P, Efros AA, Research BA. Unpaired Image-to-Image
Translation Using Cycle-Consistent Adversarial Networks Monet Photos.;
2017. Accessed November 9, 2022. https://github.com/junyanz/CycleGAN.