Electrical Conductivity Characteristics of Glioma: Noninvasive Assessment by MRI and Its Validity
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 scan1. Preliminary studies have suggested its potential usefulness in grading glioma and differentiation between meningioma and lymphoma2,3. Nevertheless, the former was performed on a small number of glioma patients and included patients who were already undergoing treatment2. Regarding validity of noninvasive σ measurement by EPT, tests of validation have been successfully done with normal saline and chicken breast phantoms3,4; 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 mm3), 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= (2μ0ω)-1ΔΦ, where μ0=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 environment5,6. 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 cells6. 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

1. Katscher U, Kim DH, Seo JK. Recent progress and future challenges in MR electric properties tomography. Comput Math Methods Med 2013; 2013: 546562

2. Tha KK, Stehning C, Suzuki Y, et al. Noninvasive Evaluation of Electrical Conductivity of the Normal Brain and Brain Tumors. Proc Intl Soc Mag Reson Med 2014: 22

3. Tha KK, Katscher U, Stehning C, et al. Electrical Conductivity Characteristics of Meningiomas: Noninvasive Assessment Using Electric Properties Tomography. Proc Intl Soc Mag Reson Med 2015: 23

4. Stehning C, Voigt TR, Katscher U. Real-Time conductivity mapping using balanced SSFP and phase-based reconstruction. Proc Intl Soc Mag Reson Med 2011: 11

5. Sha K, Ward ER, Stroy B. A review of dielectric properties of normal and malignant breast tissue. In: Proc IEEE SoutheastCon; 2002: 457-461

6. Cameron IL, Smith NK, Pool TB, Sparks RL. Intracellular concentration of sodium and other elements as related to mitogenesis and oncogenesis in vivo. Cancer Res 1980: 40; 1493

Figures

Figure 1: The σ descriptors of gliomas. Mean ± SD are given. * and ** indicate pairs with significance (P<0.05). A case (Anaplastic oligodendroglioma; Grade 3) in which the contrast-enhanced (white arrow) and non-contrast-enhanced (pink arrow) tumor components and normal brain parenchyma are distinguishable by σ characteristics is also given.

Figure 2: σ of different glioma grades as measureable by EPT. Pair with statistical significance (P<0.05) is shown. Mean ± SD are given.

Figure 3: Correlation between a σ descriptor and Ki67. The lines indicate mean and 95% confidence interval. Examples of Grade 2 to Grade 4 gliomas (FLAIR images and σ maps) are given. Ki67 of Grade 2, 3, and 4 gliomas are 2, 6.2, and 33, respectively. Arrows indicate tumors.

Figure 4: Correlation between σ of glioma measureable by EPT and that measured by a dielectric probe. The lines indicate mean and 95% confidence interval. * indicates normalized ratio by the mirror VOI on the contralateral normal brain parenchyma.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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