Khin Khin Tha1,2, Ulrich Katscher3, Shigeru Yamaguchi4, Shunsuke Terasaka4, Toru Yamamoto5, Kohsuke Kudo2,6, and Hiroki Shirato1,2
1Department of Radiobiology and Medical Engineering, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 2Global Institution for Quantum Medical Science and Engineering, Hokkaido University, Sapporo, Japan, 3Research Laboratories, Hamburg, Germany, 4Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 5Graduate School of Health Sciences, Sapporo, Japan, 6Hokkaido University Hospital, Sapporo, Japan
Synopsis
Electric
Properties Tomography was performed in 24 glioma patients, and the electrical
conductivity characteristics of glioma were determined noninvasively.
Diagnostic performance of electrical conductivity in distinguishing glioma
grades was also evaluated. Validity of noninvasive electrical conductivity
measurement was proved by correlating with the conductivity values measured ex
vivo by a dielectric probe.Background and Purpose
Electric
Properties Tomography (EPT) is a recently developed technique which estimates
electrical conductivity (σ) of tissues noninvasively and in vivo, from the phase
images of an MRI scan
1. Preliminary studies have suggested its potential usefulness
in grading glioma and differentiation between meningioma and lymphoma
2,3. Nevertheless,
the former was performed on a small number of glioma patients and included patients
who were already undergoing treatment
2. Regarding validity of noninvasive σ
measurement by EPT, tests of validation have been successfully done with normal
saline and chicken breast phantoms
3,4; but validation of σ of tumor measured
in vivo by EPT with that by ex vivo measurement using a dielectric probe has not
yet been tested. The purposes of this study were two folds: (1) to determine
the electrical conductivity characteristics of glioma in treatment-naïve patients, and (2) to test correlation between σ of glioma
measured in vivo using EPT and that measured ex vivo using a dielectric probe.
Methods
This
study included 24 treatment-naïve glioma patients with confirmed diagnosis (8
Grade II, 8 Grade III, and 6 Grade IV). EPT was performed with a Steady-State Free Precession (SSFP) sequence
with non-selective RF pulse (TR/TE/α/NEX=3.5 ms/ 1.7 ms/ 25°/2, Voxel size=1.3 x 1.2 x 1
mm
3), using a 3T scanner (Achieva TX, Philips Medical Solutions, Best, the Netherlands). Axial pre- and post-contrast-enhanced T1WI,
T2WI, and FLAIR imaging were also performed. σ maps were constructed from the phase images of
EPT, using the formula σ= (2μ
0ω)
-1ΔΦ, where μ
0=mean magnetic
permeability of the body, ω=Larmour frequency, Δ=Laplacian operator, and Φ=transceive
phase. In each patient, the contrast-enhanced (CE) and non-contrast-enhanced
(NCE) tumor components, and normal-appearing brain parenchyma (N) were segmented
semiautomatically, from the pre- and post-contrast-enhanced T1WI, T2WI, and
FLAIR images. These components were then superimposed onto the σ maps coregistered with the other images. The major
histogram metrics were derived, and compared among the components and tumor
grades. Friedman with posthoc Wilcoxon tests or one way ANOVA and posthoc LSD
tests were used to determine significance. Receiver-operating characteristic
(ROC) analysis was also performed to determine accuracy in grading glioma. Correlation
between the histogram metrics of each component and tumor proliferation index
(Ki67) was also tested. Correlation between σ of glioma
measured in vivo using EPT and that measured ex vivo using a dielectric probe (N1500A, Keysight Technologies,USA) was tested in 11 patients, in whom
tissue sample of the tumor was available for ex vivo measurement. For
correlation analyses, Pearson’s product-moment correlation analysis was used to
determine significance.
Results
For all tumor grades, the mean σ was significantly
different among the CE and NCE tumor components and N (P<0.05). The CE
component mostly had the highest mean σ,
followed by NCE component. Mode of σ of CE and NCE tumor components of Grade
III and Grade IV gliomas was significantly higher than N (P<0.05) (Figure 1). Grade IV gliomas had
significantly higher mode of σ of
the NCE component than the Grade III gliomas (P<0.05), and tended to have
higher value than Grade II gliomas (Figure 2). ROC analysis revealed that, with a
cut-off value of 914.41 mS/m, mode of σ of
the NCE component would distinguish Grade IV gliomas from the other grades with
80% sensitivity and 86% specificity. The normalized mode of σ of NCE tumor component showed
significant strong positive correlation with Ki67 (r=0.65, P=0.01)(Figure 3). Significant
strong positive correlation was also observed between the normalized mode of σ of NCE tumor component and σ measured by dielectric probe
(r=0.73, P=0.01)(Figure 4).
Discussion
The
observed σ difference
between glioma and N is thought to be due to destruction of cell membranes that
results in loss of insulating barriers and increase in sodium ion concentration
and/ or content in the tumor environment
5,6. The σ difference among
the tumor components and N may imply that EPT can be used to identify tumor and
allows tumor segmentation. The σ of NCE
component may distinguish Grade IV gliomas from the lower grade gliomas which
have better prognosis, with high sensitivity and specificity. Increase in σ with
increase in Ki67 is thought to be due to high sodium concentration within the
rapidly proliferating tumor cells
6. This is the first report which validates the
noninvasive σ
measurement of gliomas. Failure to observe significant correlation between σ of CE
component and that measured by dielectric probe may be due to limited sample
size (50% of Grade II gliomas did not enhance).
Conclusions
This study determined the electrical conductivity characteristics of
glioma noninvasively and in vivo, and validated noninvasive σ measurement of glioma by EPT.
Acknowledgements
This
study was supported by the grant-in-aid for scientific research (KAKENHI-26461817) and the Global Institution for Collaborative
Research and Education (GI-CoRE), Hokkaido University.References
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