Nonthermal irreversible electroporation for intracranial surgical applications

Laboratory investigation

Restricted access

Object

Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue.

Methods

The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced.

Results

The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain.

Conclusions

The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.

Abbreviation used in this paper: NTIRE = nonthermal irreversible electroporation.

Article Information

Address correspondence to: Rafael V. Davalos, Ph.D., School of Biomedical Engineering and Sciences, Virginia Tech, 329 ICTAS Building, Stanger Street (MC 0298), Blacksburg, Virginia 24061. email: davalos@vt.edu.

Please include this information when citing this paper: published online June 18, 2010; DOI: 10.3171/2010.5.JNS091448.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Photograph showing the blunt-tip dual probe insertion during the intracranial NTIRE procedure.

  • View in gallery

    Dog 1. Ultrasonographic images obtained intraoperatively but pre-NTIRE treatment (A) and 24 hours post-NTIRE treatment (B). The NTIRE ablation zone is clearly visible as a well-demarcated, hypoechoic circular lesion (small arrowhead) with a hyperechoic rim (large arrowheads). ESG = ectosylvian gyrus; LV = lateral ventricle.

  • View in gallery

    Magnetic resonance images obtained immediately after the procedure in Dogs 1 (A and B, 1600 V, 8-mm electrode separation), 2 (C and D, 1000 V, 5-mm electrode separation), and 3 (E and F, 500 V, 5-mm electrode separation). The left panels are T2-weighted images, and the right panels are T1-weighted contrast-enhanced images.

  • View in gallery

    Magnetic resonance images obtained 48 hours after the procedure in Dogs 3 (A and B, 500 V) and 2 (C and D, 1000 V). The left panels are T2-weighted MR images, and the right panels are T1-weighted contrast-enhanced images. All images correspond to a 5-mm electrode separation.

  • View in gallery

    Photomicrographs of normal canine brain at the surface (A and D) and deep (G) levels, sham study to isolate the mechanical effects of electrode insertion at the surface (B and E) and deep (H) levels, and the NTIRE effect on brain at the surface (C and F) and deep (I) levels. H & E, original magnification × 75 (A–C), and × 150 (D–I).

  • View in gallery

    Photomicrographs of NTIRE-treated brains. In Dog 2, a very sharp transition zone between necrotic and normal tissue (A) and sparing of major blood vessels (B) are shown. In control (Dog 4), a thrombus was detected (C). H & E.

  • View in gallery

    Photomicrograph. In this section of brain, taken at the site of NTIRE treatment, there is moderate diffuse perivascular and intraglial edema, as well as death of neuronal and glial cells. Modest reactive gliosis is seen. The treatment area is infiltrated with mixed inflammatory cells, including neutrophils, macrophages, plasma cells, and small lymphocytes. This section is representative of the NTIRE treatment area. H & E, original magnification × 40.

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