MRI Study on Reversible and Irreversible Electroporation Induced Blood Brain Barrier Disruption

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.

[1]  Thomas L Ellis,et al.  Nonthermal irreversible electroporation for intracranial surgical applications. Laboratory investigation. , 2011, Journal of neurosurgery.

[2]  Gabriel A Silva,et al.  Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS , 2008, BMC Neuroscience.

[3]  Helen Kavnoudias,et al.  Irreversible Electroporation: A New Challenge in “Out of Operating Theater” Anesthesia , 2010, Anesthesia and analgesia.

[4]  B. Locke,et al.  Magnetic resonance studies of laryngeal tumors implanted in nude mice: effect of treatment with bleomycin and electroporation. , 2002, Magnetic resonance imaging.

[5]  Boris Rubinsky,et al.  In vivo electrical impedance measurements during and after electroporation of rat liver. , 2007, Bioelectrochemistry.

[6]  S. Maier,et al.  Convection-enhanced drug delivery: increased efficacy and magnetic resonance image monitoring. , 2005, Cancer research.

[7]  T. Obata,et al.  Visualization of in vivo electroporation-mediated transgene expression in experimental tumors by optical and magnetic resonance imaging , 2009, Gene Therapy.

[8]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.

[9]  J A Frank,et al.  Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines. , 2006, AJNR. American journal of neuroradiology.

[10]  B Rubinsky,et al.  Irreversible electroporation on the small intestine , 2012, British Journal of Cancer.

[11]  C. Pfueller,et al.  Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study. , 2012, Archives of neurology.

[12]  M Bikson,et al.  DBS-relevant electric fields increase hydraulic conductivity of in vitro endothelial monolayers , 2010, Journal of Neural Engineering.

[13]  G. Vassal,et al.  Poly(ethylene glycol)-Coated Hexadecylcyanoacrylate Nanospheres Display a Combined Effect for Brain Tumor Targeting , 2002, Journal of Pharmacology and Experimental Therapeutics.

[14]  B. Bhanu,et al.  Automated ischemic lesion detection in a neonatal model of hypoxic ischemic injury , 2011, Journal of magnetic resonance imaging : JMRI.

[15]  J. Weaver,et al.  Theory of electroporation: A review , 1996 .

[16]  Boris Rubinsky,et al.  Irreversible Electroporation: Implications for Prostate Ablation , 2007, Technology in cancer research & treatment.

[17]  S. Bagla,et al.  Percutaneous irreversible electroporation of surgically unresectable pancreatic cancer: a case report. , 2012, Journal of vascular and interventional radiology : JVIR.

[18]  Yang Guo,et al.  MR imaging to assess immediate response to irreversible electroporation for targeted ablation of liver tissues: preclinical feasibility studies in a rodent model. , 2010, Radiology.

[19]  L. Mir Bases and rationale of the electrochemotherapy , 2006 .

[20]  David J Mikulis,et al.  Neuro MR: Protocols , 2007, Journal of magnetic resonance imaging : JMRI.

[21]  D. Scherman,et al.  Muscle transfection and permeabilization induced by electrotransfer or pluronic L64: Paired study by optical imaging and MRI. , 2010, Biochimica et biophysica acta.

[22]  Jiangyang Zhang,et al.  Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury , 2012, Journal of Neuroinflammation.

[23]  Boris Rubinsky,et al.  Magnetic Resonance Imaging Characteristics of Nonthermal Irreversible Electroporation in Vegetable Tissue , 2010, The Journal of Membrane Biology.

[24]  B. Rubinsky,et al.  Endovascular nonthermal irreversible electroporation: a finite element analysis. , 2010, Journal of biomechanical engineering.

[25]  Boris Rubinsky,et al.  Irreversible Electroporation: A New Ablation Modality — Clinical Implications , 2007, Technology in cancer research & treatment.

[26]  Damijan Miklavčič,et al.  Advanced Electroporation Techniques in Biology and Medicine , 2010 .

[27]  Rafael V. Davalos,et al.  Intracranial Nonthermal Irreversible Electroporation: In Vivo Analysis , 2010, The Journal of Membrane Biology.

[28]  K. Hynynen,et al.  Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. , 2008, Ultrasound in medicine & biology.

[29]  S E Maier,et al.  Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging. , 2001, Cancer research.

[30]  Rafael V. Davalos,et al.  Successful treatment of a large soft tissue sarcoma with irreversible electroporation. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Boris Rubinsky,et al.  In vivo results of a new focal tissue ablation technique: irreversible electroporation , 2006, IEEE Transactions on Biomedical Engineering.

[32]  V M Runge,et al.  Gd DTPA: a review of clinical indications in central nervous system magnetic resonance imaging. , 1989, Radiographics : a review publication of the Radiological Society of North America, Inc.

[33]  Boris Rubinsky,et al.  Nonthermal irreversible electroporation for tissue decellularization. , 2010, Journal of biomechanical engineering.

[34]  Richard Heller,et al.  In vivo electroporation for gene therapy. , 2006, Human gene therapy.

[35]  Boris Rubinsky,et al.  The Effect of Irreversible Electroporation on Blood Vessels , 2007, Technology in cancer research & treatment.

[36]  V. Runge The Use of MR Contrast in Nonneoplastic Disease of the Brain , 1995, Topics in magnetic resonance imaging : TMRI.

[37]  Helle K. Iversen,et al.  Diffusion-Weighted MRI for Verification of Electroporation-Based Treatments , 2011, The Journal of Membrane Biology.

[38]  James C. Weaver,et al.  Electroporation of cells and tissues , 2000 .

[39]  M. Horsfield,et al.  Quantitative assessment of magnetic resonance imaging lesion load in multiple sclerosis. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[40]  K. Thomson,et al.  Human Experience with Irreversible Electroporation , 2010 .

[41]  Franci Demsar,et al.  CONTRAST ENHANCED MRI ASSESSMENT OF TUMOR BLOOD VOLUME AFTER APPLICATION OF ELECTRIC PULSES , 1998 .

[42]  S. Maier,et al.  Using MRI for the assessment of paraoxon‐induced brain damage and efficacy of antidotal treatment , 2012, Journal of applied toxicology : JAT.

[43]  Boris Rubinsky,et al.  Tumor Ablation with Irreversible Electroporation , 2007, PloS one.

[44]  M. Bureau,et al.  In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle , 2005, Gene Therapy.