Jun-Hyeok Lee1, Hyeong-Geol Shin2,3, Minjun Kim2, Jongho Lee2, and Se-Hong Oh1
1Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Korea, Republic of, 2Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of, 3Johns Hopkins University School of Medicine & Kennedy Krieger Institute, Baltimore, MD, United States
Synopsis
Keywords: Software Tools, Quantitative Susceptibility mapping, Chi-separation
The susceptibility maps generated by QSM and $$$\chi$$$-separation show magnetic susceptibility distributions, which have
been proposed as important biomarkers for brain disorders. However,
susceptibility mapping requires a complicated multi-step procedure that is difficult
for inexperienced researchers. There is a need to design a convenient
application that can easily conduct susceptibility mapping. In this work, we
developed a MATLAB based GUI software, called the ‘$$$\chi$$$-separation toolbox’ that generates
high-quality susceptibility maps in just a few clicks. The GUI of our toolbox is intuitive
and user-friendly that it helps researchers to conduct QSM and $$$\chi$$$-separation processing without difficulty.
Introduction
Quantitative Susceptibility
Mapping (QSM) is an advanced MR imaging technique which provides distribution
of magnetic susceptibility in the brain. Several studies suggested QSM can be a
biomarker for neurological disorders1-6, such as multiple sclerosis
and Parkinson’s disease. The QSM result includes both positive and negative
susceptibilities. Since iron and myelin have opposite magnetic susceptibility characteristics,
the separation of positive and negative susceptibility sources can help the
accurate diagnosis. Recently, Shin et al developed $$$\chi$$$-separation7
technique which can measure individual contributions of paramagnetic and
diamagnetic susceptibility sources by formulating the biophysical model and
solving the minimization problem. The results of the experiments demonstrated
that $$$\chi$$$-separation successfully separated the
two sources. However, as shown in Fig. 1, susceptibility
mapping requires a complicated procedure that is difficult for inexperienced
researchers or clinicians. There is a need to design a convenient tool that can
easily conduct $$$\chi$$$-separation.
In this work, we developed a MATLAB based GUI
software, called the ‘$$$\chi$$$-separation toolbox’ to generate high-quality
susceptibility maps without using command line. The ‘$$$\chi$$$-separation
toolbox’ provides high-quality QSM map as well as positive and
negative susceptibility maps. Methods
Figure 2 illustrates the main GUI window of the ‘$$$\chi$$$-separation
toolbox’. It consists of setting, display, and start panels. The $$$\chi$$$-separation
and QSM processing starts with the setting panel. In the setting panel one can
load input data. For the input data, Dicom, Nifti and Mat file formats are
available. Then, reconstruction parameters (e.g., B0 direction, echo-time, and
resolution) and methods (e.g., an iterative sparse linear equation and
least-squares (iLSQR)
9 and QSMnet
10,11 for QSM; L1-norm
regularization (L1), streaking artifact suppression (SA),
and $$$\chi$$$-sepnet
12 for $$$\chi$$$-separation) need to be set up. In the start panel, users can
select and start desired processes (e.g., phase unwrapping, background field
removal, QSM, and $$$\chi$$$-separation). The processed results are saved in the output
directory and seen in the display panel. The setting panel consists of 5 tabs
as listed below. The users can control data input/output, method selection and
parameters setting for corresponding processes in each tab.
- Phase unwrapping:
processing to calculate the total field map from the phase. This process uses
the Laplacian-based method8,9.
- Background field removal:
processing to calculate the tissue field from the total field map. This process
uses the Variable-kernel SHARP (V-SHARP)9 to remove the background
field.
- QSM: processing to
calculate the susceptibility map from the tissue field. This process uses the
iLSQR method9 or a deep learning-based method, called QSMnet10.
- $$$\chi$$$-separation: processing to
separate positive and negative susceptibility sources. This process uses the $$$\chi$$$-separation7 or a deep learning-based method, called $$$\chi$$$-sepnet12.
- Common: Setting parameters
and information common to all processes. It is available to put data parameters
such as B0-direction, echo-time, and resolution, and to load STI Suite and MEDI
toolbox directory.
$$$\chi$$$-separation formulate a new biophysical model
to separate magnetic susceptibility sources as follows
7:
$$argmin_{\chi_{pos},\chi_{neg}}\left\|W_{\mathbf{r}}\cdot \{R_2'-(\overline{D_{\mathbf{r},pos}}\cdot\left|\chi_{pos}\right|-\overline{D_{\mathbf{r},neg}}\cdot\left|\chi_{neg}\right|)\}+i2\pi\cdot W_{f}\cdot \{\Delta f-D_{f}\ast(\chi_{pos}+\chi_{neg})\}\right\|_{2}^{2}+reg(\chi_{pos},\chi_{neg}),$$
where $$$\mathbf{r}$$$ is the position vector of a voxel,
$$$\Delta f$$$ is the frequency shift, $$$\chi_{pos}$$$ and $$$\chi_{neg}$$$ are
the positive and negative susceptibility sources, respectively, $$$D_{f}$$$ is the field perturbation kernel, and $$$\overline{D_{\mathbf{r},pos}}$$$ and $$$\overline{D_{\mathbf{r},neg}}$$$ are nominal relaxometric constants for the
positive and negative susceptibility sources, respectively. The optimal
solution is found using a conjugate gradient descent algorithm. Depending on
the regularization term of minimization, L1 or SA methods are available: $$$\chi$$$-separation
L1
and $$$\chi$$$-separation
SA. Since $$$\chi$$$-separation requires a R
2' calculated by subtracting R
2 from R
2*, spin
echo (SE) data in addition
to gradient echo (GRE) data are needed. We allow it possible to perform $$$\chi$$$-separation with only GRE data by generating a pseudo R
2' by subtracting a nominal masked pseudo R
2 from the R
2*: $$$\chi$$$-separation
L1*
and $$$\chi$$$-separation
SA*. $$$\chi$$$-separation code is available at https://github.com/SNU-LIST.
Our toolbox includes two types of deep learning
based $$$\chi$$$-separation method
12: $$$\chi$$$-sepnet
and $$$\chi$$$-sepnet*. Compared to $$$\chi$$$-sepnet, $$$\chi$$$-sepnet*,
a variant of $$$\chi$$$-sepnet,
doesn’t require a R
2 as an input. In
other words, $$$\chi$$$-sepnet*
doesn't need additional SE
scan for the R
2. This feature makes $$$\chi$$$-sepnet* appealing
clinical study.
Results
To validate the usability of the ‘$$$\chi$$$-separation
toolbox’, Figs. 3 - 5 illustrate processed results obtained from the ‘$$$\chi$$$-separation
toolbox’. The QSM maps calculated by COSMOS, iLSQR9, and QSMnet10 are shown in Fig.
3. The result of QSMnet shows a more similar susceptibility distribution to
that of COSMOS. Figure 4 shows $$$\chi$$$-separation
results calculated by COSMOS13, L1, SA, and $$$\chi$$$-sepnet12 with GRE data and SE data. Figure 5 shows $$$\chi$$$-separation
results calculated without SE data. $$$\chi_{pos}$$$ and $$$\chi_{neg}$$$ show high
concentration in deep gray and white matter, respectively.Discussion and Conclusion
In this study, we developed the MATLAB based GUI software, called the ‘$$$\chi$$$-separation toolbox’ that generates high-quality susceptibility maps in just a few clicks. Its GUI is intuitive and user-friendly that it helps researchers who are interested in magnetic susceptibility distribution to conduct QSM and $$$\chi$$$-separation processing without difficulty. Our toolbox provides various methods, including deep learning-based methods for susceptibility mapping pipeline. With the powerful reconstruction capability of
deep learning, $$$\chi$$$-sepnet can overcome the quality degradation of $$$\chi$$$-separation resulted from situations without SE data. Future development is to incorporate new methods to obtain susceptibility maps by combining various processes.Acknowledgements
This work was supported by the MSIT (Ministry of
Science, ICT), Korea, under the High-Potential Individuals Global Training
Program (2021-0-01553), supervised by the IITP (Institute for Information &
Communications Technology Planning & Evaluation), and the National Research
Foundation of Korea (NRF) grant, funded by the Korean government (MSIT)
(NRF-2020R1A2C4001623).References
1. Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong
VW. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev
Neurol. 2014;10(8):459-468.
2. Zecca L, Youdim MBH, Riederer P, Connor JR,
Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev
Neurosci. 2004;5(11):863-873.
3. Sowell ER, Peterson BS, Thompson PM, Welcome SE,
Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat
Neurosci. 2003;6(3):309-315.
4. McKenzie IA, Ohayon D, Li H, et al. Motor skill
learning requires active central myelination. Science. 2014;346(6207):318-322.
5. Compston A, Coles A. Multiple sclerosis. Lancet.
2008;372(9648):1502-1517.
6. Nave KA. Myelination and support of axonal
integrity by glia. Nature. 2010;468(7321):244-252.
7. Shin HG, Lee J, Yun YH, et al. χ-separation:
Magnetic susceptibility source separation toward iron and myelin mapping in the
brain. Neuroimage. 2021;240(118371):118371.
8. Schofield MA, Zhu Y. Fast phase unwrapping
algorithm for interferometric applications. Opt Lett. 2003;28(14):1194-1196.
9. Li W, Wu B, Liu C. Quantitative susceptibility
mapping of human brain reflects spatial variation in tissue composition. Neuroimage.
2011;55(4):1645-1656.
10. Yoon J, Gong E, Chatnuntawech I, et al.
Quantitative susceptibility mapping using deep neural network: QSMnet. Neuroimage.
2018;179:199-206.
11. Jung W, Yoon J, Ji S, et al. Exploring linearity
of deep neural network trained QSM: QSMnet+. Neuroimage.
2020;211(116619):116619.
12. Kim M, Shin H-G, Oh C, et al. Chi-sepnet:
Susceptibility source separation using deep neural network. International
Society for Magnetic Resonance in Medicine. 2022 May 7-12; London, England, UK:
Abstract #2464.
13. Shin H-G, Seo J, Lee Y, et al. Chi-separation
using multi-orientation data in invivo and exvivo brains: Visualization of
histology up to the resolution of 350 μm. International Society for Magnetic
Resonance in Medicine. 2022 May 7-12; London, England, UK: Abstract #8228.