Alessandro Arduino1, Francesca Pennecchi1, Ulrich Katscher2, Luca Zilberti1, and Maurice Cox3
1Istituto Nazionale di Ricerca Metrologica (INRIM), Torino, Italy, 2Philips Research Laboratories, Hamburg, Germany, 3National Physical Laboratory (NPL), Teddington, United Kingdom
Synopsis
This work shows the uncertainty evaluation under
repeatability conditions of the phase-based Helmholtz-electric properties
tomography (EPT) technique. Repeated MRI scans of a homogeneous cylindrical
phantom are analyzed with appropriate statistical techniques to evaluate the covariance
matrix of the EPT input. This matrix is propagated through the EPT technique
according to the law of propagation of uncertainty. The estimated electric
conductivity is highly repeatable and exhibits a spatial dispersion, whose
average value, within a central region, gives an accurate estimate of the
phantom conductivity. The described approach will be applied in future to
extend the characterization under reproducibility conditions.
INTRODUCTION
The assessment of the uncertainty in the outcome of
electric properties tomography (EPT) is of paramount importance to understand
the reliability of the results and to move their interpretation from an
“electric properties–weighted” to a proper quantitative imaging.
The development of a complete uncertainty budget is a
complex task that should be conducted according to the Guide to the expression
of the uncertainty in measurement1 (GUM) and related documents,2,3
taking into account uncertainty contributions originating from different
sources. The present work focuses on the repeatability contribution.
Among the EPT methods, the Helmholtz-based technique4 with phase-based approximation is here investigated due to its wider prevalence
in the clinical context.5,6,7 Since this technique is a simple
linear transformation from the “transceive” phase distribution $$$\varphi^\pm$$$ to
the map of electric conductivity $$$\sigma$$$,
the law of propagation of uncertainty1 (LPU) is applied without
approximations.METHODS
A homogeneous cylindrical phantom filled with a
solution of 3.75 g/L NaCl in distilled water was scanned 25 times with an MRI
scanner 3 T Ingenia TX (Philips Healthcare, Best, The Netherlands) and a
32-channel RF receive head-coil. A steady-state free precession (SSFP) sequence
with low flip-angle and isotropic resolution of 2 mm was used; thus, the phase
of the acquired complex images is a good approximation of $$$\varphi^\pm$$$.8 Moreover, the square root of the magnitude of the images approximates the
transmit sensitivity.9 Input data were acquired in a short time and without
moving the phantom, and hence under repeatability conditions. The nominal
(provided with no associated uncertainty) electric conductivity of the phantom
at 128 MHz is 0.56 S/m.
The phase-based Helmholtz-EPT relies on the equation4,8$$\sigma=\frac{\nabla^2\varphi^\pm}{2\omega\mu_0}\,,$$whose discrete approximation can be written as $$$\boldsymbol{s}=A\boldsymbol{f}$$$, $$$\boldsymbol{f}$$$ and $$$\boldsymbol{s}$$$ being vectors describing the three-dimensional images of $$$\varphi^\pm$$$ and $$$\sigma$$$,
respectively. Each row of the matrix $$$A$$$ is a local approximation, based on
the Savitzky–Golay filter,10 of the differential operator $$$(2\omega\mu_0)^{-1}\nabla^2$$$,
and it is characterized by the set of voxels, called kernel, used to compute it. Three kernel shapes—cross, sphere and
cube—and five sizes, $$$n=1,\dots,5$$$, are
investigated (Fig. 1). The EPTlib-0.1.111 implementation of
Helmholtz-EPT is used.
Since the phantom is homogeneous, the spatial average $$$\overline{\sigma}$$$ of $$$\boldsymbol{s}$$$ can be taken as the phantom
conductivity estimate. The generalized weighted average $$$\overline{\sigma}_w$$$, based on the
covariance matrix of $$$\boldsymbol{s}$$$, $$$\Sigma(\boldsymbol{s})=A\Sigma(\boldsymbol{f})A^T$$$, is
computed as well, being the minimum variance unbiased estimator of the expected
value. These averages are calculated, respectively, as12$$\overline{\sigma}=N^{-1}\boldsymbol{w}^T\boldsymbol{s}\,,\quad\overline{\sigma}_w=(\boldsymbol{w}^T\Sigma(\boldsymbol{s})^{-1}\boldsymbol{w})^{-1}\boldsymbol{w}^T\Sigma(\boldsymbol{s})^{-1}\boldsymbol{s}\,,$$$$$N$$$ being the size of $$$\boldsymbol{s}$$$ and $$$\boldsymbol{w}$$$ a column vector of ones.RESULTS
In order to reduce the dimensionality of the problem
and to avoid the known issues of Helmholtz-EPT near the boundaries, only the
voxels within the sphere of radius 3 cm, pictured in Fig. 2, are analyzed.
Despite that, the number of voxels remains significantly larger than the number
of scans; thus, to avoid the curse of
dimensionality, a James–Stein-type shrinkage estimator13 for the
covariance matrix $$$\Sigma(\boldsymbol{f})$$$ of the mean phase distribution $$$\boldsymbol{f}$$$ has been used. The
resulting correlations are shown in Fig. 2.
The conductivity map estimated by phase-based Helmholtz-EPT
applied to the mean of the 25 phase distributions shows a significant spatial
variability, with no regular geometrical patterns. For any kernel shape and
size, the collection of $$$\boldsymbol{s}$$$ components is summarized by boxplots
in Fig. 3. They show symmetric distributions whose dispersion is reduced by
increasing the kernel size. Fig. 3 highlights also the systematic error due to
the phase-based approximation, which is corrected by providing the magnitude of
the transmit sensitivity as an additional input to Helmholtz-EPT4,8.
The spatial averages of the electric conductivity
estimated within the sphere are collected in Fig. 4, together with their standard
uncertainties12:$$u(\overline{\sigma})=N^{-1}\sqrt{\boldsymbol{w}^T\Sigma(\boldsymbol{s})\boldsymbol{w}}\,,\quad u(\overline{\sigma}_w)=\sqrt{(\boldsymbol{w}^T\Sigma(\boldsymbol{s})^{-1}\boldsymbol{w})^{-1}}\,.$$Moreover, the standard uncertainty $$$\tilde{u}(\overline{\sigma})$$$ is computed neglecting all the correlations in $$$\Sigma(\boldsymbol{f})$$$.
All data and results are available on Zenodo14.DISCUSSION
The obtained results show that, despite a spatial
dispersion of the electric conductivity estimated by phase-based Helmholtz-EPT being
present under repeatability conditions, the average of the values recovered within
a central sphere of voxels is a stable estimate of the nominal value of the
phantom conductivity. It is weakly affected by the choice of the kernel and has
a significantly small standard uncertainty, negligible with respect to the
systematic error due to the phase-based approximation. The estimate is further
improved, both in terms of accuracy and precision, by the generalized weighted
average.
The presented study suggests that the output of
Helmholtz-EPT can be significantly improved by applying appropriate
post-processing filters, like some kind of local averaging. In clinical
investigations, for example, a median filter was adopted for cases
in which the in vivo application forced the adoption of filtering volumes
locally adapted to the anatomy, in order not to cross the tissue boundaries5.CONCLUSION
A metrologically sound assessment of uncertainty in
EPT has been performed under repeatability conditions with a homogeneous
phantom. The obtained results show the relevance of post-processing the EPT output
in order to improve the reliability. Future research will extend the proposed
assessment to reproducibility conditions and heterogeneous domains.Acknowledgements
The project 17NRM05 “Examples of Measurement
Uncertainty Evaluation” leading to this application has received funding from
the EMPIR programme co-financed by the Participating States and from the
European Union’s Horizon 2020 research and innovation programme.References
1. BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP, and OIML. Guide to the
Expression of Uncertainty in Measurement, JCGM 100:2008, GUM 1995 with minor
corrections. BIPM, 2008.
2. BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP, and OIML. Supplement 1 to the
‘Guide to the Expression of Uncertainty in Measurement’ – Propagation of
distributions using a Monte Carlo method, JCGM 101:2008. BIPM, 2008.
3. BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP, and OIML. Supplement 2 to the
‘Guide to the Expression of Uncertainty in Measurement’ – Extension to any
number of output quantities, JCGM 102:2011. BIPM, 2011
4. Voigt T, Katscher U, and Doessel O. Quantitative conductivity and
permittivity imaging of the human brain using electric properties tomography.
Magn Reson Med. 2011; 66:456–466.
5. Tha KK, Katscher U, Yamaguchi S, et al. Noninvasive electrical
conductivity measurement by MRI: a test of its validity and the electrical conductivity
characteristics of glioma. Eur Radiol. 2018; 28:348–355.
6. Shin J, Kim MJ, Lee J, et al. Initial study on in vivo conductivity mapping
of breast cancer using MRI. J Magn Reson Imaging. 2015; 42:371–378.
7. Kim S-Y, Shin J, Kim D-H, et al. Correlation between conductivity and
prognostic factors in invasive breast cancer using magnetic resonance electric properties
tomography (MREPT). Eur Radiol. 2016; 26:2317–2326.
8. Katscher U, Kim D-H, Seo JK. Recent progress and
future challenges in MR electric properties tomography. Computational and
mathematical methods in medicine. 2013; 546562.
9. Lee S-K, Bulumulla S, Wiesinger F, et al. Tissue electrical property
mapping from zero echo-time magnetic resonance imaging. IEEE transactions on
medical imaging. 2015; 34:541–550.
10. Savitzky A, Golay MJE. Smoothing and differentiation of data by
simplified least squares procedures. Analytical chemistry. 1964; 36:1627–1639.
11. Arduino A. EPTlib 0.1.1. https://eptlib.github.io/, 2020. Accessed: 2020-09-25.
12. Cox MG, Eiø C,
Mana G, Pennecchi F. The generalized
weighted mean of correlated quantities. Metrologia. 2006; 43:S268–S275.
13. Schafer J, Opgen-Rhein R, Zuber V, et al. corpcor 1.6.9: Efficient
Estimation of Covariance and (Partial) Correlation.
http://www.strimmerlab.org/software/corpcor/, 2017. Accessed: 2020-09-29.
14. Arduino A, Pennecchi F, Zilberti L, et al. EMUE-D5-3-EPTTissueCharacterization.
https://zenodo.org/communities/emue, 2020. Accessed: 2020-11-04.