The Optimization of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma

Thank you for your attention!

The Future

Motivation

“Cancer will affect 1 in 2 men and 1 in 3 women in the United States…”

-Both predictions are based on statistics collected by the Surveillance Epidemiology and End Results (SEER) program at the National Cancer Institute (NCI)

-MedScape Medical News, 2007

Hepatocellular Carcinoma

(HCC)

3rd most common cause of cancer death

6th most common cancer

Highest incidence:

• China
• Southeast Asia
• Sub-saharan Africa

Causes

• ~80% due to liver cirrhosis
• Hepatitis B,C
• Aflatoxin

image from From Reddy, Scientific Basis for Medicine Lecture 204, Feinberg SOM, 2009

Acknowledgements

Possible Treatments

• Sahakian Lab
• Haitham Al-Angari, PhD
• Ilya Mikhelson, BS, MS
• Wendy Yip BS, MS

• MSTP
• Dane Chetkovich, MD, PhD
• Hossein Ardehali, MD, PhD
• Sarah Rice, PhD
• Rebecca Cooper, Carmen Hoffman

• National Cancer Institute
• F31 CA150658

The Optimization of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma

• 80% cases not treatable with surgery/transplant

• 19,000 patients on transplant list at any given time

image from From Reddy, Scientific Basis for Medicine Lecture 204, Feinberg SOM, 2009

• Optimize Pulse parameters
• Minimize heating
• Validate with animal experiments

HCC Therapies

Ablation

Irreversible Electroporation

Radiofrequency

Ablation

Cryoablation

Ethanol

Injection

Selective Internal Radiation Therapy

Oyinlolu Adeyanju

Advisor: Alan Sahakian, PhD

Chemical

Chemoembolization

Chemotherapy

Conclusions

Catheter-directed Treatments

copy paste branches if you need more....

• Chemotherapy
• Ethanol Injection

• Transarterial Chemoembolization
• Selective Internal Radiation Therapy

• Radiofrequency Ablation
• Cryoablation
• Irreversible Electroporation

Electrode configurations

• Two electrodes is best
• Minimize distance between electrodes

Saline

• Saline can reduce temperature at electrodes
• Not dependent upon conductivity
• Can increase lower temperatures (flattening of heat curve)

(cc) photo by theaucitron on Flickr

Studies Conducted

Results

Electrode Configurations

(Adeyanju et al. 2012, Radiology and Oncology)

+

and

COMSOL

->

V-IRE

Saline studies

Problem

Optimize Electrode Positioning

Quadratic Relationship Between V-IRE and Distance

Electrode Placement

(Adeyanju et al. 2012, Radiology and Oncology)

1st step

Quadratic Relationship Between V-ANT and Distance

(Adeyanju et al. 2012, Radiology and Oncology)

IRE

Electroporation

Irreversible Electroporation (IRE)

• Affects Cell membrane
• Creates aqueous pores
• Can be reversible or irreversible

• Quick
• Effective
• Sharp demarcation between affected and unaffected regions
• Leaves tissue structure intact
• Nerves, blood vessels, bile duct, etc.

Research Plan

Finished

Optimization Algorithm

genetic algorithm

Gradient-based methods

Steepest-descent

Newton's method

Preliminary Work

(Adeyanju et al. 2012, Radiology and Oncology)

• can more easily avoid local optima
• may take longer

parameters

• mutation rate
• initial population size
• crossover rate
• maximum number of generations

+

and

COMSOL

requires calculation of gradient

requires calculation of Hessian

->

Last step

V-IRE

Hypothesis: faster but possibly less accurate than genetic algorithm

• tendency to get stuck in local optima
• more costly calculations

output

input

• distance between electrodes
• depth of electrode insertion
• search parameters OR polynomial equation

Problem

• optimal electrode position
• time
• accuracy (% difference from previous results)

Complete Computational System for Calculating Electrode Placement

Optimize Electrode Positioning

Quadratic Relationship Between V-IRE and Distance

Aim 2

Aim 1

Electrode Placement

(Adeyanju et al. 2012, Radiology and Oncology)

Optimization Algorithm

Automated conversion tool for medical images->3D COMSOL objects

1st step

Search-based methods

Gradient-based methods

Steepest-descent

Newton's method

genetic algorithm

• mutation
• mating/crossover
• natural selection

time+accuracy

Quadratic Relationship Between V-ANT and Distance

(Adeyanju et al. 2012, Radiology and Oncology)