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

Authors

  • Faisal Mahmood Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, University of Copenhagen, Herlev Hospital, Herlev, Denmark; Radiotherapy Research Unit (RRU), Department of Oncology, University of Copenhagen, Herlev Hospital, Herlev, Denmark
  • Rasmus H. Hansen Department of Radiology, University of Copenhagen, Herlev Hospital, Herlev, Denmark
  • Birgit Agerholm-Larsen Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, University of Copenhagen, Herlev Hospital, Herlev, Denmark;Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark
  • Hanne Gissel Institute of Biomedicine, Aarhus University, Aarhus C, Denmark
  • Per Ibsen Department of Pathology, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark
  • Julie Gehl Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, University of Copenhagen, Herlev Hospital, Herlev, Denmark

DOI:

https://doi.org/10.3109/0284186X.2014.991045

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.

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Published

2015-03-16

How to Cite

Mahmood, F., Hansen, R. H., Agerholm-Larsen, B., Gissel, H., Ibsen, P., & Gehl, J. (2015). Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI. Acta Oncologica, 54(3), 289–297. https://doi.org/10.3109/0284186X.2014.991045

Issue

Vol. 54 No. 3 (2015): Acta Oncologica

Section

Articles