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Dynamic effects of point source electroporation on the rat brain tissue
Shirley Sharabi1, David Last2, David Guez2
1The Advanced Technology Center, Sheba Medical Center, Ramat-Gan 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Abstract:
In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, p<0.001) and the number of treatment pulses (r(2)=0.94, p<0.002). Blood-brain barrier disruption depicted 3.2±0.3 times larger volumes than the final permanent damage volumes (p<0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.
Insights
Novel electroporation techniques show promise for treating glioblastoma multiforme. This minimally invasive approach uses intracranial electroporation and MRI to assess treatment effects, offering a new avenue for brain tumor therapy.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Oncology
Background:
- Glioblastoma multiforme (GBM) presents a poor prognosis due to invasive tumor growth and limited drug delivery across the blood-brain barrier.
- Current aggressive therapies for GBM have shown limited efficacy.
Purpose of the Study:
- To introduce a novel, minimally invasive treatment for GBM using intracranial electroporation.
- To develop a non-invasive method for assessing treatment response via magnetic resonance imaging (MRI).
Main Methods:
- A unique setup with a single intracranial electrode and an external surface electrode was used for electroporation in rat brains.
- Various electroporation protocols were applied to study physiological effects.
- Magnetic resonance imaging (MRI) was employed to assess blood-brain barrier disruption and permanent brain tissue damage volumes.
Main Results:
- Treatment voltages and the number of pulses significantly correlated with blood-brain barrier disruption and permanent brain tissue damage (r(2)=0.99 and r(2)=0.94, respectively).
- Blood-brain barrier disruption volumes were significantly larger (3.2±0.3 times) than final permanent damage volumes (p<0.0001).
Conclusions:
- Electroporation parameters, specifically voltage and pulse number, are critical determinants of treatment effects.
- Combining multiple electroporation modalities may enhance treatment efficacy for brain tumors.
- This study highlights the potential of electroporation combined with MRI for GBM treatment and assessment.
