Dynamic effects of point source electroporation on the rat brain tissue.

In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, p<0.001) and the number of treatment pulses (r(2)=0.94, p<0.002). Blood-brain barrier disruption depicted 3.2±0.3 times larger volumes than the final permanent damage volumes (p<0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.

[1]  Damijan Miklavcic,et al.  Equivalent Pulse Parameters for Electroporation , 2011, IEEE Transactions on Biomedical Engineering.

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

[3]  Rafael V. Davalos,et al.  Pilot study of irreversible electroporation for intracranial surgery , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[4]  P S Tofts,et al.  Measurement of blood‐brain barrier permeability using dynamic Gd‐DTPA scanning—a comparison of methods , 1992, Magnetic resonance in medicine.

[5]  A. Marmarou,et al.  Magnetic resonance imaging-monitored acute blood-brain barrier changes in experimental traumatic brain injury. , 1996, Journal of neurosurgery.

[6]  Thomas Pongratz,et al.  Induction of Immune Mediators in Glioma and Prostate Cancer Cells by Non-Lethal Photodynamic Therapy , 2011, PloS one.

[7]  Stephen B. Solomon,et al.  The delayed effects of irreversible electroporation ablation on nerves , 2013, European Radiology.

[8]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[9]  Paulo A. Garcia,et al.  7.0-T Magnetic Resonance Imaging Characterization of Acute Blood-Brain-Barrier Disruption Achieved with Intracranial Irreversible Electroporation , 2012, PloS one.

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

[11]  Faisal Mahmood,et al.  Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. , 2011, Cancer research.

[12]  J. Wolchok,et al.  Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response. , 2013, Surgery.

[13]  T. Neumann-Haefelin,et al.  Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue injury, blood-brain barrier damage, and edema formation. , 2000, Stroke.

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

[15]  Martin L. Yarmush,et al.  Nonthermal Irreversible Electroporation: Fundamentals, Applications, and Challenges , 2013, IEEE Transactions on Biomedical Engineering.

[16]  Boris Rubinsky,et al.  Irreversible Electroporation in Medicine , 2007, Technology in cancer research & treatment.

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

[18]  M. Bikson,et al.  Bio-Heat Transfer Model of Deep Brain Stimulation Induced Temperature changes , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[19]  James C. Weaver,et al.  Electroporation of biological membranes from multicellular to nano scales , 2003 .

[20]  H. Feng,et al.  Photodynamic therapy boosts anti‐glioma immunity in mice: A dependence on the activities of T cells and complement C3 , 2011, Journal of cellular biochemistry.

[21]  Tomaz Slivnik,et al.  Sequential finite element model of tissue electropermeabilization , 2005, IEEE Transactions on Biomedical Engineering.

[22]  Daniel J Brat,et al.  Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma , 2004, Laboratory Investigation.

[23]  Paulo A. Garcia,et al.  NON-THERMAL IRREVERSIBLE ELECTROPORATION , 2010 .

[24]  Eric Vicaut,et al.  Laser thermal therapy: Real‐time MRI‐guided and computer‐controlled procedures for metastatic brain tumors , 2011, Lasers in surgery and medicine.

[25]  Damijan Miklavcic,et al.  Feasibility of Employing Model-Based Optimization of Pulse Amplitude and Electrode Distance for Effective Tumor Electropermeabilization , 2007, IEEE Transactions on Biomedical Engineering.

[26]  Antoni Ivorra,et al.  Tissue Electroporation as a Bioelectric Phenomenon: Basic Concepts , 2010 .

[27]  Boris Rubinsky,et al.  In vivo electrical conductivity measurements during and after tumor electroporation: conductivity changes reflect the treatment outcome , 2009, Physics in medicine and biology.

[28]  H. Dvorak,et al.  VEGF‐A Angiogenesis Induces a Stable Neovasculature in Adult Murine Brain , 2004, Journal of neuropathology and experimental neurology.

[29]  Damijan Miklavcic,et al.  Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors , 2012, Medical and Biological Engineering and Computing.

[30]  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.

[31]  E. Neumann,et al.  Electrooptics of membrane electroporation and vesicle shape deformation , 1996 .

[32]  Ming Li,et al.  Argon-Helium Cryosurgery for Treatment of C6 Gliomas in Rats and its Effect on Cellular Immunity , 2010, Technology in cancer research & treatment.

[33]  B. Rubinsky,et al.  Tissue Ablation with Irreversible Electroporation , 2005, Annals of Biomedical Engineering.

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

[35]  S. Rapoport.  Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy , 2001, Expert opinion on investigational drugs.

[36]  Mojca Pavlin,et al.  Theoretical and experimental analysis of conductivity, ion diffusion and molecular transport during cell electroporation--relation between short-lived and long-lived pores. , 2008, Bioelectrochemistry.

[37]  Andrew H. Kaye,et al.  Photodynamic therapy of high grade glioma – long term survival , 2005, Journal of Clinical Neuroscience.

[38]  D. Gomez-Nicola,et al.  Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System , 2011, Clinical Medicine Insights. Oncology.

[39]  B. Birlik,et al.  Tumour vascularity is of prognostic significance in adult, but not paediatric astrocytomas , 2006, Neuropathology and applied neurobiology.

[40]  Boris Rubinsky,et al.  MRI Study on Reversible and Irreversible Electroporation Induced Blood Brain Barrier Disruption , 2012, PloS one.