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Research Papers: Bio-Heat and Mass Transfer

Treatment of Uveal Melanoma by Nonthermal Irreversible Electroporation: Electrical and Bioheat Finite Element Model of the Human Eye

[+] Author and Article Information
Yossi Mandel

Center for Bioengineering in the Service of Humanity and Society,  School of Engineering and Computer Science, Hebrew University of Jerusalem, 91904 Israelyossi.mandel@gmail.com

Boris Rubinsky

Department of Mechanical Engineering, Graduate Program in Biophysics,  University of California at Berkeley, Berkeley, CA 94720brubinsky@gmail.com

J. Heat Transfer 134(11), 111101 (Sep 28, 2012) (9 pages) doi:10.1115/1.4005203 History: Received February 26, 2011; Revised September 14, 2011; Published September 28, 2012; Online September 28, 2012

Nonthermal irreversible electroporation (NTIRE) is an new minimally invasive tissue ablation modality that uses high electric field pulses to produce irreversible permeation of the cell membrane (irreversible electroporation) while avoiding thermal damage and is applied to treat malignant tumors. This paper describes efforts to develop NTIRE as a new minimally invasive treatment modality for uveal melanoma, the most common primary intraocular malignancy in adults, and other ocular malignancies. The paper deals with a 3D mathematical simulation model of the eye that employs the simultaneous solution to the electric field equation and to the Pennes bioheat equation to predict the electric field in the eye as well as the rise in eye temperature in response to the application of a high power electric pulse. Treatment efficacy was defined as the fraction of tumor volume in which the electric field exceeded a predefined target field and treatment safety was calculated by the ratio of the electric field in the tumor to the electric field in the vitreous humor or in the macula. Results show that treatment efficacy and safety are criteria that can be used to optimize the NTIRE treatment protocol.

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Copyright © 2012 by American Society of Mechanical Engineers
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Figures

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Figure 1

A schematic figure of the human eye with the various subdomains comprising the analyzed model

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Figure 2

The five electrode configurations used in the present simulation study. Configurations #1, #2, #3, #5 were composed of a combination of internal and external electrode. Configuration #4 was composed of external only ring-shape scleral electrodes, which are positioned on the outer sclera, opposite the sclera facing the tumor.

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Figure 3

The initial temperature distribution of the eye (T0) is depicted in color scale, as well as in a graph demonstrating a significant gradient in the inner eye temperature

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Figure 4

The white area represents tumor area in which the electric field exceeds 1000 V/cm in five electrode configurations. Pulse potential was 1000 V/cm, tumor conductivity was 0.17 S/m.

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Figure 5

Fraction of tumor within electric field targets (500, 800, 1000 V/cm) are depicted against the pulse potential for five electrode configurations. Triangles, open diamonds, and asterisks represent field targets of 500, 800, and 1000 V/cm, respectively.

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Figure 6

The fraction of tumor within the target field of 1000 V/cm is depicted against vitreous electric field for five electrode configurations

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Figure 7

(a) Fraction of tumor volume in which the electric field is larger than 1000 V/cm as a function of the pulse potential for electrodes configurations #1, #3, and #4 is depicted for five tumor conductivities. Each electrode configuration is marked with one symbol. The five curves for each electrode configuration were calculated for tumor electrical conductivities of 0.332 S/m factorized by 0.25, 0.5, 1, 1.5, and 2 from top curve to bottom. (b) The fraction of tumor volume with electric fields exceeding 1000 V/cm as a function of tumor conductivity factor (the ratio between tumor conductivity to normal tumor conductivity) for electrode configurations #1, #3, and #4.

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Figure 8

Maximum (dashed lines) and average (solid temperature) temperature ( °C) are plotted against time (s) in seven ocular domains following two electrical pulses with pulse repetition frequency of 0.1 Hz, pulse duration 10 × 10−5 s, electrode configuration #4, pulse potential 2000 V

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Figure 9

Sclera, retina, and tumor maximum (dashed lines) and average (solid line) temperature ( °C) are plotted against time (s) for 90 electrical pulses with pulse repetition frequency of 1 Hz, pulse duration 10 × 10−5 s, electrode configuration #4, pulse potential 2000 V. The blurred maximal temperature line depicts the large variations in domain temperature during and between pulses.

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Figure 10

The combined effect of pulse duration and pulse repetition frequency on maximal scleral temperature in three electrode configurations. Maximal scleral temperature after 90 pulses of treatment is depicted against pulse repetition frequency and pulse duration. For better demonstration of temperature dependent on pulse parameters the Z axis (maximal scleral temperature) is limited to 70  °C although in some settings it was several hundred Celsius.

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