Stefano Mandija1,2, Petar Petrov3, Jord Vink3, Sebastian Neggers3, and Cornelis A.T. van den Berg1,2
1Computational Imaging Group for MR diagnostic and therapy, Center for Image Sciences, University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Radiotherapy, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands, 3Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands
Synopsis
First
in-vivo brain conductivity reconstructions have been recently published.
However, a large variation in the reconstructed conductivity values is reported
and these results substantially differ from ex-vivo measurements. Given this
lack of agreement, we performed an in-vivo study on eight healthy subjects to
provide reference brain conductivity values.
The
measured in-vivo mean WM and GM conductivity values verify for the first time
the literature values measured ex-vivo, while the reconstruction accuracy was
verified in simulation settings. The presented values can therefore be used as
a verified in-vivo reference for future studies, where new reconstruction
algorithms are tested in-vivo.
Introduction
Electrical
Properties Tomography (EPT) is an MR-based technique used to non-invasively quantify
tissue conductivity (σ) and permittivity (εr,). First in-vivo results have been
recently published.
However,
as highlighted by two published reviews[1,2], the
number of studies showing in-vivo reconstructions is very low, and, for brain
tissues, the number of subjects is also limited[3,4,5,6].
Next to the scarce amount of in-vivo brain reconstructions, the presented
results lack agreement. A large variation in the reconstructed conductivity
values is reported (possibly caused by the different reconstruction algorithms),
and these results substantially differ from ex-vivo values.
Given
this lack of agreement, we performed an in-vivo study to provide reference
in-vivo brain conductivity values of the white and gray matter (WM, GM).Methods
MRI
measurements were performed on eight healthy volunteers (mean age 21.7,
standard deviation 2.3) using a 3T MR-scanner (Achieva, Philips, Best, NL) and
a 8-channel transmit/receive head coil.
Conductivity
reconstructions were performed according to[7]: σ(r)=Im((ΔB1+(r))/B1+(r))/μ0ω, with ω=Larmor frequency, μ0=free space permeability, and r=x,y,z-coordinates.
The B1+ magnitude was measured using a 3D-dual-TR sequence8 (Figure 1).
For the B1+ phase, the transceive phase
approximation was employed[9] by combining two phase maps acquired using
2D-single-echo Spin-Echo sequences with opposite readout gradient polarities (Figure 1). Gibbs-ringing correction and
k-space Gaussian apodization were performed to minimize the impact of undesired
high frequency spatial fluctuations[7].
Second order spatial derivatives were
computed using
a large, noise-robust, in-plane derivative
kernel (Klarge: 7x7 voxels)[7]. An
in-plane kernel had to be used since well-known random phase offsets between
slices prevented correct computations of spatial derivatives through slices.
First, mean and standard deviation of σWM, σGM, and σCSF were computed
for each subject.
Tissue segmentation was performed in SPM12
using the Spin-Echo magnitude volumes.
Only the voxels with a probability value (P) > 99% to belong to a
certain tissue were considered, thus avoiding voxels with partial volumes.
Then, mean and standard
deviation of σWM, σGM were computed for each subject after additional erosion (2 voxels
erosion) of the WM and GM masks previously obtained from SPM12 was performed in order to
avoid regions at tissue boundaries that are affected by typical MR-EPT boundary
errors.
To benchmark the accuracy of these reconstructions, conductivity
reconstructions were similarly performed using FDTD
simulated complex B1+ data (Sim4Life, Duke head
model, Figure 1), as simulated data
allows knowledge of the ground truth conductivity. Gaussian noise was also included to
mimic the SNR level obtained in the MR measurements. The mean σWM and σGM among 50
reconstructions with different noise realizations were computed over the whole
head model, after the same in-plane erosion used for the in-vivo
reconstructions was applied. Results and Discussion
Figure 2 shows one slice of
the reconstructed conductivity maps for the 8 subjects.
Figure 3 shows that mean conductivity values are erroneous if boundary erosion is not
performed. Instead, provided sufficient boundary
erosion, mean σWM and σGM values are
in good agreement with the reported literature values measured ex-vivo.
This
indicates that:
1) boundary erosion is crucial for correct quantification of
mean conductivity values;
2) the way boundaries are handled has severe impact
on the reconstructed mean conductivity values.
This latter observation might be
the reason why the few in-vivo data reported in literature are so different, as
boundaries are differently handled among different studies.
Unfortunately,
this erosion cannot be applied to the CSF due to its limited spatial extension.
Smaller resolutions and small kernels should be adopted to correctly quantify σCSF, but this would lead to conductivity
maps completely corrupted by noise. Hence, given the absence of a gold standard
for in-vivo MR-EPT reconstructions, we believe that the agreement between σWM and σGM among eight subjects
achieved in this work gives confidence on in-vivo σWM
and σGM values
for healthy subjects.
The
results from simulations, performed to benchmark the accuracy of the
reconstruction pipeline, are reported in Figure
4, where the reconstructed conductivity is shown for one slice, as well as the mean σWM and σGM values
of the whole Duke head computed after the same erosion applied for the in-vivo conductivity
reconstructions was performed. The mean σWM and σGM values among 50 reconstructions
with different noise realizations agree with the reconstructed values in-vivo.
However, these values show a small underestimation (~10%)
with respect to the input ground truth. This is caused by the fact that
the conductivity contribution arising from derivatives through slices are
neglected, as these derivatives cannot be computed for the in-vivo case. This also explains the negligible underestimation
in the reconstructed in-vivo σWM and σGM values with
respect to literature ex-vivo values.Conclusions
Boundary
erosion is crucial to correctly quantify mean conductivity values. If
boundaries are not handled correctly, erroneous mean conductivity values are
obtained. This might explain the large variability among the brain conductivity
values reported in literature.
The
in-vivo σWM and σGM values
obtained in this study verify for the first time the literature values measured
ex-vivo, while the accuracy of the
reconstruction procedure was verified in simulation settings.
The presented σWM and σGM values can
therefore be used as a verified reference for future studies where new
reconstruction algorithms are tested in-vivo.Acknowledgements
No acknowledgement found.References
1) Katscher
U., van den Berg C.A.T., Electric
properties tomography: Biochemical, physical and technical background,
evaluation and clinical applications. NMRinBiomed 2017, DOI: 10.1002/nbm3729.
2) Hancu
I., Liu J., Hua Y., Lee S.K., Electrical
properties tomography: Available contrast and reconstruction capabilities. MRM 2018, DOI: 10.1002/mrm.27453.
3) Zhang X., Van de Moortele P.F., Schmitter S., He B.. Complex
B1 mapping and electrical properties imaging of the human brain using a
16‐channel transceiver coil at 7T. MRM 2013, DOI: 10.1002/mrm.24358.
4) Voigt T.,
Katscher U., Doessel
O.. Quantitative
conductivity and permittivity imaging of the human brain using electric
properties tomography. MRM 2011,
DOI: 10.1002/mrm.22832.
5) Huhndorf
M., Stehning C., Rohr A., et al., Systematic
Brain Tumor Conductivity Study with Optimized EPT Sequence and Reconstruction
Algorithm. ISMRM, Salt Lake City 2013. p. 3626.
6) Tha
K.K., Katscher U., Yamaguchi S., et al. Noninvasive electrical conductivity measurement by MRI: a test of its
validity and the electrical conductivity characteristics of glioma. European
Radiology 2018: 348-355.
7) Mandija
S., Sbrizzi A., Katscher U., Luijten P.R., van den Berg C.A.T.,Error analysis of Helmholtz‐based MR‐electrical properties tomography. MRM 2018, DOI: 10.1002/mrm.27004.
8) Yarnykh, V. L.. Actual
flip‐angle imaging in the pulsed steady state: A method for rapid
three‐dimensional mapping of the transmitted radiofrequency field. MRM 2007, DOI: 10.1002/mrm.21120.
9) van Lier A., Brunner D.O., Pruessmann K.P., Klomp D.W.,
Luijten P.R., Lagendijk J.J., van den Berg C.A.T.. B1+ Phase
mapping at 7 T and its application for in vivo electrical conductivity mapping. MRM 2012, DOI: 10.1002/mrm.22995.
10) SPM12,
WTCN, UCL, London, UK