Yiran Li1, Danfeng Xie1, Dushyant Kumar2, Abigail Cember2, Ravi Prakash Reddy Nanga2, Hari Hariharan2, John A. Detre3, Ravinder Reddy2, and Ze Wang1
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, 2Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States, 3Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
Synopsis
This study presents a DL based framework for correcting B0 inhomogeneity for GluCEST imaging
using fewer acquisitions. Based on 3 or 5 positive offset CEST images, the proposed method can save >80% of CEST imaging acquisition time as compared
to current 26 pairs of double site z-spectrum irradiations based protocol. This
approach can be applied to other CEST imaging as well.
Introduction
Glutamate weighted Chemical Exchange Saturation
Transfer (GluCEST) MRI is a noninvasive technique for mapping parenchymal
glutamate in the brain [1-4]. GluCEST signal is sensitive to magnetic field
(B0) inhomogeneity. Corrections for B0 inhomogeneity often require sampling
both sides of the z-spectrum at different saturation offsets, which prolongs
the total acquisition time and can cause practical issues such as increased
sensitive to patient motion [5][6]. Using deep learning (DL), we have recently
shown the capability of correcting the B0-inhomogeneity induced confounds in
GluCEST using less than half of z-spectrum samples with higher
signal-to-noise-ratio (SNR) than the non-DL method. That capability is based on
the smoothness of the z-spectrum, which allows a reliable data interpolation
based on a few sample points. In this study, we extend that capability by predicting
both the positive and negative 3ppm signal from a few downfield offset images.
Our rationale is that the positive offset images contain both the background
signal (B) and the CEST contrast (C), making it possible to use a DL network to
learn the nonlinear transform from B+C to B. In other words, the negative
offset images can be predicted from the positive offset images.Methods
The same data published in [7] were used. 29 sets of
GluCEST scans were collected from seven subjects in a 7T Siemens scanner, with twenty scans being used as training data sets and
nine scans being used as the test data sets. A full z-spectrum sampling at 26 offsets
along the upfield and downfield side of the z-spectrum (from ±1.8 to ±4.2 ppm
with a step size of 0.2 ppm) were acquired to provide a B0 correction reference
for training the DL network. The original DL based method only used 1/3/5/7
pairs of samples instead of the full set of 13 pairs [7]. However, all the
samples from negative spectrum were skipped in our proposed method. Fig. 1
shows the network structure of DL-B0GlueCEST-HS (half spectrum). The input is a
variable number of downfield offset images and the
B0 inhomogeneity map. The same interpolation block of the original DL-B0GluCEST-pair
[7] was used to get a roughly corrected saturation image to be fed into the
next block for finer processing. The middleware block contains two sub-DL
networks: one for predicting the z-spectrum sample at 3 ppm; the other for
-3ppm. Both sub-networks used the same configuration shown in Fig. 2, which is
the Wide-activation Deep Super-Resolution network (WDSR) [8]. To assess the
sensitivity of DL-B0GluCEST to the number of offset acquisitions, separate
experiments were performed by taking1, 3, 5, or 7 different downfield
z-spectrum offset images as the input. The corresponding DL-B0GluCEST-HSs trained
were named DL-B0GluCEST-HS1, 3, 5, and DL-B0GluCEST-HS7, respectively. Training
reference was obtained from the full set of 26 offset images at both sides of
the z-spectrum using current non-DL based B0 correction method. DL-B0GluCEST
with 1, 3, 5, 7 pairs of positive and negative ppm saturation images were
trained as a comparison. Method performance was measured by Structural
Similarity Index Measure (SSIM), Peak Signal-to-Noise Ratio (PSNR), and
Contrast-to-Noise Ratio (CNR). CNR was measured by the ratio of the subtraction
between the mean value of a gray matter region-of-interest (ROI) and a white
matter (WM) ROI and standard deviation of a WM ROI [9]. Higher SSIM, PSNR and
CNR indicates better image reconstruction quality.Results
Fig 3 shows the performance indices of different
methods. DL-B0GluCEST-HS1-7 performed similarly to their counterpart: DL-B0GluCEST-1-7pair
(the previous B0 correction method with different pairs of positive/negative
offset acquisitions), respectively. DL-B0GluCEST-HS1 showed the worst
performance compared to other DL-B0GluCEST-HSs. DL-B0GluCEST-HS5 and DL-B0GluCEST-HS7
had slightly better SSIM than DL-B0GluCEST-HS3, and all DL-B0GluCEST-HSs yielded
similar PSNR and CNR values. Fig 4 shows GluCEST maps from one representative
subject. The results produced by traditional method [10] are used as reference.
As shown in the first row, reducing z-spectrum sampling from 26 pairs to
7/5/3/1 pair positions dramatically reduced SNR of the GluCEST contrast maps
generated with the traditional method. By contrast, all DL methods produced
high quality results in terms of tissue structure and contrast when 3 or more
offset images or 3 or more pairs of offset images were acquired.Discussion
CEST contrast is generally
estimated from images acquired with opposite offset RF irradiations. Negative
offset images are acquired to control the background signal due to
magnetization transfer and direct water saturation; positive offset images are
supposed to modulate the positive image by additional signal originated from
protons of interest. Using DL, our data showed that it is possible to predict the
negative offset (3ppm here for glutamate) images from the B0 inhomogeneity map
and positive offset (downfield RF irradiations) images. As it is impossible to estimate
an analytical model for this complex and nonlinear transform, a supervised machine
learning provides an ideal solution. The use of spatial correlations among
neighboring voxels during the convolutional learning in the DL network
contributed to improved quantification quality. Conclusion
Based on 3 or 5 positive offset CEST images,
DL-B0GluCEST-HS can save >80% of CEST imaging acquisition time as compared
to current 26 pairs of double site z-spectrum irradiations based protocol. This
approach can be applied to other CEST imaging as well. Acknowledgements
This
project was supported by the National Institute of Biomedical Imaging and
Bioengineering of the National Institute of Health under award number
p41EB015893 and the National Institute of Drug Abuse of the National Institutes
of Health under award number R01DA037289, and by NIH/HIA R01AG060054-01.References
1. Forsén, S., Hoffman, R.A.: Study of
moderately rapid chemical exchange reactions by means of nuclear magnetic
double resonance. J. Chem. Phys. 39, 2892–2901 (1963).
2. Ward, K.M., Aletras, A.H., Balaban,
R.S.: A new class of contrast agents for MRI based on proton chemical exchange
dependent saturation transfer (CEST). J. Magn. Reson. 143, 79–87 (2000).
3. Zhou, J., Van Zijl, P.C.: Chemical
exchange saturation transfer imaging and spectroscopy. Prog. Nucl. Magn. Reson.
Spectrosc. 48, 109–136 (2006).
4. Cai, K., Haris, M., Singh, A.,
Kogan, F., Greenberg, J.H., Hariharan, H., Detre, J.A., Reddy, R.: Magnetic
resonance imaging of glutamate. Nat. Med. 18, 302–306 (2012).
https://doi.org/10.1038/nm.2615.
5. Kim, M., Gillen, J., Landman, B.A.,
Zhou, J., Van Zijl, P.C.M.: Water saturation shift referencing (WASSR) for
chemical exchange saturation transfer (CEST) experiments. Magn. Reson. Med. An
Off. J. Int. Soc. Magn.Reson. Med. 61, 1441–1450 (2009).
6. Sun, P.Z., Farrar, C.T., Sorensen,
A.G.: Correction for artifacts induced by B0 and B1 field inhomogeneities in
pH-sensitive chemical exchange saturation transfer (CEST) imaging. Magn. Reson.
Med. An Off. J. Int. Soc. Magn. Reson. Med. 58, 1207–1215 (2007).
7. Li, Yiran, Danfeng Xie, Abigail
Cember, Ravi Prakash Reddy Nanga, Hanlu Yang, Dushyant Kumar, Hari Hariharan et
al. "Accelerating GluCEST imaging using deep learning for B0
correction." Magnetic Resonance in Medicine (2020).
8. Yu, J., Fan, Y., Yang, J., Xu, N.,
Wang, Z., Wang, X., Huang, T.: Wide activation for efficient and accurate image
super-resolution. arXiv Prepr.arXiv1808.08718. (2018).
9. Welvaert, Marijke, and Yves Rosseel.
"On the definition of signal-to-noise ratio and contrast-to-noise ratio
for fMRI data." PloS one 8, no. 11 (2013): e77089.
10. Nanga, R.P.R., DeBrosse, C., Kumar,
D., Roalf, D., McGeehan, B., D’Aquilla, K., Borthakur, A., Hariharan, H.,
Reddy, D., Elliott, M., Detre, J.A., Epperson, C.N., Reddy, R.: Reproducibility
of 2D GluCEST in healthy human volunteers at 7 T. Magn. Reson. Med. (2018).