Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI

Faisal Mahmood, Rasmus H Hansen, Birgit Agerholm-Larsen, Hanne Gissel, Per Ibsen, Julie Gehl

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Abstract

BACKGROUND: Tissue permeabilization by electroporation (EP) is a promising technique to treat certain cancers. Non-invasive methods for verification of induced permeabilization are important, especially in deep-seated cancers. In this study we evaluated diffusion-weighted magnetic resonance imaging (DW-MRI) as a quantitative method for detecting EP-induced membrane permeabilization of brain tissue using a rat brain model.

MATERIAL AND METHODS: Fifty-four anesthetized Sprague-Dawley male rats were electroporated in the right hemisphere, using different voltage levels to induce no permeabilization (NP), transient membrane permeabilization (TMP), and permanent membrane permeabilization (PMP), respectively. DW-MRI was acquired 5 minutes, 2 hours, 24 hours and 48 hours after EP. Histology was performed for validation of the permeabilization states. Tissue content of water, Na+, K+, Ca2+, and extracellular volume were determined. The Kruskal-Wallis test was used to compare the DW-MRI parameters, apparent diffusion coefficient (ADC) and kurtosis, at different voltage levels. The two-sample Mann- Whitney test with Holm's Bonferroni correction was used to identify pairs of significantly different groups. The study was approved by the Danish Animal Experiments Inspectorate.

RESULTS AND CONCLUSION: Results showed significant difference in the ADC between TMP and PMP at 2 hours (p<0.001) and 24 hours (p<0.05) after EP. Kurtosis was significantly increased both at TMP (p<0.05) and PMP (p<0.001) 5 minutes after EP, compared to NP. Kurtosis was also significantly higher at 24 hours (p<0.05) and 48 hours (p<0.05) at PMP compared to NP. Physiological parameters indicated correlation with the permeabilization states, supporting the DW-MRI findings. We conclude that DW-MRI is capable of detecting EP-induced permeabilization of brain tissue and to some extent of differentiating NP, TMP and PMP using appropriate scan timing.

Original languageEnglish
JournalActa Oncologica
Volume54
Issue number3
Pages (from-to)289-97
Number of pages9
ISSN0284-186X
DOIs
Publication statusPublished - 2015

Keywords

  • Animals
  • Body Water
  • Brain
  • Brain Chemistry
  • Calcium
  • Cell Membrane Permeability
  • Diffusion
  • Diffusion Magnetic Resonance Imaging
  • Electroporation
  • Extracellular Fluid
  • Male
  • Normal Distribution
  • Potassium
  • Rats, Sprague-Dawley
  • Sodium
  • Statistics, Nonparametric
  • Time Factors

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