Synopsis
Due to their extreme noise
amplification, current Quantitative Conductivity Mapping (QCM) techniques
require high SNR images. Simultaneous Quantitative Susceptibility Mapping and
QCM uses low-SNR gradient-echo sequences, creating a need for QCM methods
appropriate for noisy images. Here we proposed, optimised, and compared several
new QCM methods (all shared on https://xip.uclb.com/i/software/MRI_conductivity.html) built on the widely-used phase-based formula
and its equivalent, less popular integral form. We found that solving the
integral equation provided lower errors and better edge preservation in both
simulated and in-vivo images, and that edge preservation combining magnitude-based
and image-segmentation-based techniques resulted in the best in-vivo
conductivity map.
Purpose
Quantitative Conductivity Mapping (QCM) is a non-invasive technique that calculates the tissue
electrical conductivity from the B1 phase ($$$\varphi_0$$$)1. Tissue conductivity ($$$\sigma$$$) may provide new information on
sodium levels2, and can distinguish between different types of brain
glioma3.
In state-of-the-art QCM, $$$\varphi_0$$$ is
usually acquired using high signal-to-noise ratio (SNR) sequences1,4,5,
but some studies6-8 have begun to apply simultaneous Quantitative
Susceptibility Mapping (QSM) and QCM using gradient-echo (GRE) imaging. To
compensate for the low SNR of GRE, these studies use Gaussian filtering, reducing
the apparent resolution. Here we propose, optimise, and compare new QCM methods
for low-SNR data to expand the applicability of QCM to low-SNR sequences and
facilitate further studies into simultaneous QSM/QCM.Theory
The
following differential equation is a
widely-used approximation1, valid in regions with slowly varying $$$\sigma$$$:
$$\sigma=(\mu_0\omega)^{-1}\cdot\nabla^2\varphi_0\quad[1]$$
$$$\mu_0=$$$vacuum permeability, $$$\omega=$$$Larmor frequency, and $$$\nabla^2=$$$Laplacian
operator. Applying a finite-difference approximation of $$$\nabla^2$$$ (Figure 1a) severely amplifies the
noise9, especially in low-SNR data (Figure 5a). One widely-used
noise suppression method involves fitting a 3D quadratic function within a
kernel around each voxel and calculating the Laplacian of these fitted functions5,10
(Figure 1b). However, this results in blurring near the conductivity boundaries
(Figure 5b) where Equation 1 is not applicable.
It has been suggested previously that the integral form11 of Equation 1 is more noise robust12:
$$\sigma=(V\mu_0\omega)^{-1}\cdot\int_S\nabla\varphi_0d\textbf{s}\quad[2]$$
where $$$S$$$ is the closed surface
of some kernel with volume $$$V$$$.
Previous studies have used
i) Equation 1 with large kernels combined with either magnitude-based weighting5
(Mag) (Figure 1c) or magnitude-based image segmentation13 (Seg)
(Figure 1d) for better edge preservation, or ii) Equation 2 only with small
kernels to avoid errors at the conductivity boundaries11-12 (Figure 1a).
Here we implemented Equations
1 and 2 using large kernels restricted by the magnitude (Mag) and/or the
segmentation (Seg) (Figure 1b-e).Methods
Multi-echo GRE brain images (Figure 2, bottom) were
acquired in a healthy volunteer at 3T14 (Prisma, Siemens) using a 64-channel
RF coil with FOV=22×22×13 cm3, 1.5 mm isotropic resolution, TR=4370
ms, and α=90°. ASPIRE15 was used on the first two echoes (TE1=5
ms and TE2=10 ms) to estimate $$$\varphi_0$$$ (the
phase at TE=0 ms) for each channel which were then combined using scalar phase
matching16. Gray matter (GM), white matter (WM), and the
cerebrospinal fluid (CSF) were segmented using SPM1217 on the
combined magnitude image at TE=0 ms (extrapolated using an exponential fit
followed by bias field correction18). The SNR was calculated as the
ratio of the extrapolated $$$M_0$$$ mean and standard deviation within WM.
Realistic conductivity11,
permittivity11, and signal magnitude ($$$M$$$) values were assigned
to an anthropomorphic numerical brain
phantom19,20 with 1 mm isotropic resolution (Figure 2, top). The
noise-free B1 phase, $$$\phi_0$$$, was calculated from the phantom
conductivity and permittivity maps using established 3D electromagnetic simulations21-23.
The incident electric field was defined as the field generated by an infinitely
long, 16-rung, 60-cm-diameter, quadrature birdcage coil. Noisy
magnitude, $$$m$$$, and $$$\varphi_0$$$ were simulated by adding Gaussian noise to the real and imaginary
components of the complex signal, $$$M\cdot\exp(i\phi_0)$$$ matching
the SNR (=16) of the phantom to the in-vivo image.
Conductivity maps were
calculated from the in-vivo and simulated $$$\varphi_0$$$ using
all 10 methods in Figure 1 and optimal kernel radii determined by finding the
minimum mean absolute error throughout the numerical brain phantom (Figures 3a-b
and 4a-c) where true derivatives were calculated from the noise-free $$$\phi_0$$$. Results
Figure 5 shows the optimised
conductivity maps for the numerical phantom (top) and the in-vivo images
(bottom). Compared to using a large kernel (5b), all conductivity maps had
substantially improved edge preservation and errors using either Mag and/or
Seg (5c-e). The integral-based approaches (5c-e) provided much sharper
edges (white rectangles) and lower mean absolute errors than the
differential-based methods, possibly because calculating the first derivatives
amplifies the noise less (hence the smaller optimal kernel) than calculating
the Laplacian. Increasing the kernel radius (for either the 3D quadratic fit or
the surface integral) leads to inaccuracies even in the noise-free cases
(Figures 3c and 4d). Therefore, the optimal kernel radii represent a trade-off
between noise suppression and conductivity accuracy. Note that we optimised the
kernel sizes throughout the brain which led to some additional conductivity
underestimation in the ventricles (Figure 4c, white arrows) in exchange for
more accurate GM conductivity (Figure 4c, black arrows). In the phantom, the ventricles were
more attenuated when solving Equation 2 (Figure 5e, white arrows). This could be because the surface integral uses $$$\nabla\varphi_0$$$ values from the conductivity boundary (that
the kernel follows for Mag+Seg) where the electromagnetic simulations were inaccurate (see boundary artifacts in $$$\nabla^2\phi_0$$$, Figure 3c arrows). On the contrary, the integral-based Mag+Seg approach provided
the most realistic (i.e. highest) ventricle conductivity in vivo (Figure 5e,
black arrows). Future work will repeat the experiment with $$$\phi_0=(\mu_0\omega)\cdot\nabla^{-2}\sigma$$$ providing
a less realistic but boundary-artifact-free phantom.Conclusions
Here, we developed, optimised, and compared different approaches for
phase-based conductivity mapping in noisy images. We found that solving the
integral-form (Equation 2) provided lower errors and better edge preservation
in both simulated and in-vivo images. The integral-based approach with both magnitude- and segmentation-restricted kernels provided the best in-vivo conductivity map. All methods we developed are downloadable from https://xip.uclb.com/i/software/MRI_conductivity.html.Acknowledgements
We would like to thank Dr Barbara Dymerska, Beata Bachrata, and Dr
Simon Robinson for providing the in-vivo images. We are grateful to Dr Patrick
Fuchs for his help with the electromagnetic simulations and Dr Ulrich Katscher
for his insightful feedback.
Dr Anita Karsa and Dr Karin Shmueli were supported by European Research
Council Consolidator Grant DiSCo MRI SFN 770939.
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