INSPIRE Therapy

Integrated nanosecond pulse irreversible electroporation (INSPIRE) is an exciting new cancer therapy which destroys tumors using bursts of electric pulses.

Bursts of high voltage (1000 - 6000 V) pulses are delivered directly into the tumor for 100 seconds, destroying the tumor cells while leaving blood vessels, nerves, and other critical structures intact.

Our laboratory specializes in the development of the high voltage electronics required to to treat tumors clinically. Starting with the size and location of common patient tumors, we derive the device specifications required to destroy these tumors in a single treatment. Then custom electronics and electrodes are designed, built, and tested in our laboratory. Investigations are underway for the treatment of liver, breast, kidney, pancreatic, and brain tumors between 1 - 6 cm.

These systems are capable of generating a variety of output waveforms including traditional monopolar IRE pulses and INSPIRE bursts with constitutive pulses between 250 nanoseconds and 100 microseconds.

They are completely software controlled and include advanced safety systems including automated arc detection which can shut off the system in as little as 3.4 microseconds after an arc occurs.

We use complex computational models to examine how different pulses affect treatment outcomes. Promising techniques are then tested in vitro, as shown above, before being implemented in vivo. We have found that there are multiple strategies which enhance the lethality of INSPIRE treatments and enable us to treat larger tumors. Modulating the waveform symmetry is a promising technique, in addition to increasing the voltage, duration, and energy of treatment bursts, for improving treatment outcomes.

INSPIRE is a non-thermal tissue ablation therapy. However, some tissue heating can occur so treatment planning is used to ensure that the temperature does not cause thermal damage.

Sub-lethal pulses can also be used to disrupt the blood brain barrier. This technique may be beneficial for the treatment of brain cancer or to increase the efficacy of neurological therapies which have difficulty crossing the blood brain barrier.

Live (green - Calcein AM) and dead (red - Propidium Iodide) prostate cancer cells in a 3D tumor mimic after INSPIRE treatment. This rapid therapy allows us to destroy cancer cells within a well defined volume.

Sub-lethal electroporation can be used to transport large molecules into cells. As a proof of concept, Phallodin, which is unable to passively enter the cell, is transported under a sub-lethal electric field, allowing it to bind to actin filaments (green).

Publications:

	Optimization of a Single Insertion Electrode Array for the Creation of Clinically Relevant Ablations Using High-Frequency Irreversible Electroporation Computers in Biology and Medicine - 2018 [Download] [Supplemental Material]
	Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High Frequency Bursts of Alternating Polarity Pulses Journal of Vascular and Interventional Radiology (JVIR) - 2018
	Treatment of Cancer In Vitro Using Radiation and High-Frequency Bursts of Submicrosecond Electrical Pulses IEEE Transactions on Biomedical Engineering - 2017 [Download ] [Supplemental Material]

	A Comprehensive Characterization of Parameters Affecting High-Frequency Irreversible Electroporation Lesions Annals of Biomedical Engineering - 2017 [Download] [Supplemental Material]

	Irreversible electroporation for the ablation of pancreatic malignancies - A patient-specific methodology Journal of Surgical Oncology - 2017 [Download]

	Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies Nature Scientific Reports - 2017 [Supplemental Materials]

	Production of Spherical Ablations using Non-Thermal Irreversible Electroporation Journal of Vascular and Interventional Radiology (JVIR) - 2016

	Targeted Cellular Ablation Based on the Morphology of Malignant Cells Nature Scientific Reports - 2015

	Bursts of Microsecond Pulses Inhibit Tumor Growth Nature Scientific Reports - 2015

	In-Vitro Bipolar Nano-and Microsecond Electro Pulse Bursts for Irreversible Electroporation Therapies Bioelectrochemistry - 2014

	Focal blood-brain-barrier disruption with high-frequency pulsed electric fields Technology - 2014

	High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction Biomedical Engineering Online - 2011

	Theoretical considerations of tissue electroporation with high-frequency bipolar pulses IEEE Transactions on Biomedical Engineering - 2011

	Towards the creation of decellularized organ constructs using irreversible electroporation and active mechanical perfusion Biomedical Engineering Online - 2010
	An experimental investigation of temperature changes during electroporation Proceedings of the International Union of Radio Science

Patents:

	Methods for enhancing and modulating reversible and irreversible electroporation lesions by manipulating pulse waveforms US 15/616737 [Download]
	Selective Modulation of Intracellular Effects of Cells Using Pulsed Electric Fields US 15/310114 [Download]
	System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies US 14/558,631 [Download]
	Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment PCT/US2015/065792 [Download]
	High-frequency electroporation for cancer therapy PCT/US2011/066239 - US 13/332,133 [Download]
	Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds US 13/989,175 - PCT/US2011/062067 [Download]

Michael B. Sano, Ph.D.

mikesano at unc.edu