MRI study on reversible and irreversible electroporation induced blood brain barrier disruption

• Published in: PloS one Vol. 7; no. 8; p. e42817
• Main Authors: Hjouj, Mohammad, Last, David, Guez, David, Daniels, Dianne, Sharabi, Shirley, Lavee, Jacob, Rubinsky, Boris, Mardor, Yael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-08-2012; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Blood; Blood-brain barrier; Blood-Brain Barrier - injuries; Brain; Brain - pathology; Cell death; Damage; Diffusion barriers; Disruption; Electric fields; Electrodes; Electroporation; Electroporation - methods; Engineering; Feasibility studies; Gadolinium; Gene therapy; Image enhancement; Inflammation; Magnetic Resonance Imaging; Male; Medicine; NMR; Nuclear magnetic resonance; Rats; Tumors; Ultrasonic imaging; United States > US; Israel; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042817

Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode and cell death in the irreversible (IRE) mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE), serial SPGR (DCE-MRI) with flip angles ranging over 5-25°, and diffusion-weighted MRI (DWMRI). Blood brain barrier (BBB) disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887±83 (arbitrary units) immediately post treatment to 2246±94 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289±87. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.27±0.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50±10% of the T2W enhancing volumes on the day of the treatment which was 33±5% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions and treatment parameters.