In new research, ECT treatment planning technology devised by researchers from the University of Ljubljana in Slovenia has been extended for application to other electroporation-based therapies. The technology can now be used for irreversible electroporation (IRE), a tissue ablation method where stronger fields induce permanent membrane defects and cell death, and gene electrotransfer for gene therapy and gene vaccination (GET), where DNA is transported into cells (Phys. Med. Biol. 57 5425).

Flexible planning tool

Effective and safe electroporation requires the careful selection of several parameters, including the electrode geometry used to apply the electric field and the amplitude of the electric pulses. But while simple guidelines have proved effective for ECT in small, superficial tumours, more complex treatment scenarios require a more involved approach. The extended, advanced planning technology will assist in both the routine clinical application and research.

"It will be possible to correlate predicted outcomes with treatment results, which will open the way for a formal validation and improvement of numerical models of electroporation. With this improvement, it will be possible to improve treatment planning procedures even further and thus ensure optimal treatment for the patients," said first author, electrical engineer Anze Zupanic.

The researchers' planning system has three key components. The first is a geometrical model of the patient anatomy, created using CT or MRI data. The second is a mathematical model that calculates the extent of reversible and irreversible electroporation generated by a given treatment configuration. The third is an iterative optimization algorithm that tunes the treatment parameters and identifies the optimum treatment plan for a given case.

The algorithm scores the suitability of a given plan using a fitness function. Scores are dictated by the weighted volumes of healthy and diseased tissue that are reversibly or irreversibly electroporated, as predicted by the mathematical model. Weighting factors are chosen for each volume according to clinical intent. For example, factors for ECT plan optimization heavily weight the volume of tumour reversibly electroporated, the clinical goal, while negatively weighting the volume of irreversibly electroporated, damaged healthy tissue.

New weighting factors

In their latest study, the researchers extended the planning technology for use with IRE and GET by devising new weighting factors for both. For example, in the case of IRE, weighting factors were altered to produce high fitness function scores for plans satisfying the clinical goal of irreversible electroporation of a high tumour volume and a low volume of healthy tissue. The researchers tested the new functions by generating IRE, GET and ECT treatment plans for a single clinical case of a melanoma metastasis in a thigh. They produced three plans for each technique with four, five and six electrodes in each.

Electroporation of the entire tumour volume was achieved in all plans, though significant variations were observed in the voltages required, the electric currents generated and the optimal electrode positions. Electrode voltages were significantly greater for IRE compared to ECT, as expected, but the optimal treatment geometries for the two applications were similar. Six electrodes achieved electroporation of the tumour volume with minimum damage to adjacent healthy tissue in both applications. In contrast, GET was optimal with four electrodes, which provided minimum irreversible electroporation in the tumour and an associated maximum gene expression.

The researchers also developed visualization tools to assist treatment planning. These included a colour plot of maximum electric field strength induced by the applied electric fields that, when superimposed on CT data, provide a surrogate for electroporation distribution. Cumulative volume-field strength plots analogous to radiotherapy dose volume histograms were also devised. Senior author Damijan Miklavcic and his co-researchers are hopeful the visualization tools will be accepted by the electroporation community and become more widely implemented.