Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI
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Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI. / Mahmood, Faisal; Hansen, Rasmus H; Agerholm-Larsen, Birgit; Gissel, Hanne; Ibsen, Per; Gehl, Julie.
In: Acta Oncologica, Vol. 54, No. 3, 2015, p. 289-97.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI
AU - Mahmood, Faisal
AU - Hansen, Rasmus H
AU - Agerholm-Larsen, Birgit
AU - Gissel, Hanne
AU - Ibsen, Per
AU - Gehl, Julie
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Body Water
KW - Brain
KW - Brain Chemistry
KW - Calcium
KW - Cell Membrane Permeability
KW - Diffusion
KW - Diffusion Magnetic Resonance Imaging
KW - Electroporation
KW - Extracellular Fluid
KW - Male
KW - Normal Distribution
KW - Potassium
KW - Rats, Sprague-Dawley
KW - Sodium
KW - Statistics, Nonparametric
KW - Time Factors
U2 - 10.3109/0284186X.2014.991045
DO - 10.3109/0284186X.2014.991045
M3 - Journal article
C2 - 25591820
VL - 54
SP - 289
EP - 297
JO - Acta Oncologica
JF - Acta Oncologica
SN - 1100-1704
IS - 3
ER -
ID: 162684998