Molecular medicine requires the introduction of specific molecules, such as gene constructs or molecular drugs, specifically designed to treat diseases, into targeted cells in the body. Often, these molecules cannot penetrate the cell membrane. The use of electrical pulses to permeabilize the cell membrane to these molecules (electroporation) is becoming one of the most important methods for delivering non-permeant molecules into cells. Currently, all methods of delivering molecular medicine, including electroporation, are performed without real-time control. This means that at this stage the only indication on the outcome of the treatment is long-term, such as the much later expression or the lack of expression of a gene or the cure or lack of cure of the cancer in the patient. Obviously, this leads to inefficient treatment of the disease and is a severe drawback to molecular medicine. Here, a solution is proposed. It is suggested that the effective opening of the cell membrane with electroporation will result in changes in the electrical impedance of the electroporated tissue. It is proposed that this can be detected and even imaged in real time with electrical impedance tomography (EIT); which is an imaging technique that maps the electrical impedance of tissue to produce an image. Therefore combining electroporation with EIT may provide the system with real time control over the localization and effectiveness of the delivery of molecular medicine. The goal of this study is to developed and demonstrate the technology of EIT of electroporation. To this end we will first study the electrical properties of liver and muscle tissue as a function of the electroporated state of the tisue. Than we will develop and test an EIT system for imaging electroporation, in vitro. The final stage of the project will be a test of the ability of EIT to image and control electroporation in vivo. We anticipate that at the end of this study there will be a device available for clinical tests in patients, for investigating molecular medicine. Our work could significantly enhance the safety, efficiency and control over the delivery of molecular medicine.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR018961-04
Application #
7253112
Study Section
Special Emphasis Panel (ZRG1-DMG (90))
Program Officer
Friedman, Fred K
Project Start
2004-09-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$364,213
Indirect Cost
Name
University of California Berkeley
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Maor, Elad; Ivorra, Antoni; Mitchell, James J et al. (2010) Vascular smooth muscle cells ablation with endovascular nonthermal irreversible electroporation. J Vasc Interv Radiol 21:1708-15
Ivorra, Antoni; Al-Sakere, Bassim; Rubinsky, Boris et al. (2009) In vivo electrical conductivity measurements during and after tumor electroporation: conductivity changes reflect the treatment outcome. Phys Med Biol 54:5949-63
Maor, Elad; Ivorra, Antoni; Rubinsky, Boris (2009) Non thermal irreversible electroporation: novel technology for vascular smooth muscle cells ablation. PLoS One 4:e4757
Granot, Yair; Ivorra, Antoni; Maor, Elad et al. (2009) In vivo imaging of irreversible electroporation by means of electrical impedance tomography. Phys Med Biol 54:4927-43
Ivorra, Antoni; Shini Ast, Mohanad; Rubinsky, Boris (2009) Linear superposition electrical impedance tomography imaging with multiple electrical/biopsy probes. IEEE Trans Biomed Eng 56:1465-72
Granot, Yair; Rubinsky, Boris (2008) Mass Transfer Model for Drug Delivery in Tissue Cells with Reversible Electroporation. Int J Heat Mass Transf 51:5610-5616
Granot, Yair; Ivorra, Antoni; Rubinsky, Boris (2008) A new concept for medical imaging centered on cellular phone technology. PLoS One 3:e2075
Ivorra, Antoni; Al-Sakere, Bassim; Rubinsky, Boris et al. (2008) Use of conductive gels for electric field homogenization increases the antitumor efficacy of electroporation therapies. Phys Med Biol 53:6605-18
Granot, Yair; Rubinsky, Boris (2007) Methods of optimization of electrical impedance tomography for imaging tissue electroporation. Physiol Meas 28:1135-47
Ivorra, Antoni; Rubinsky, Boris (2007) In vivo electrical impedance measurements during and after electroporation of rat liver. Bioelectrochemistry 70:287-95

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