Design of an Irreversible Electroporation System for Clinical Use

IGEA S.r.l., Via Parmenide, 10/A, I-41012 Carpi (MO) Italy.
Technology in cancer research & treatment (Impact Factor: 1.73). 09/2007; 6(4):313-20. DOI: 10.1177/153303460700600408
Source: PubMed
Irreversible electroporation is an ablation modality in which microseconds, high-voltage electrical pulses are applied to induce cell necrosis in a target tissue. To perform irreversible electroporation it is necessary to use a medical device specifically designed for this use. The design of an irreversible electroporation system is a complex task in which the effective delivery of high energy pulses and the safety of the patient and operator are equally important. Pulses of up to 3000 V of amplitude and 50 A of current need to be generated to irreversibly electroporate a target volume of approximately 50 to 70 cm3 with as many as six separate electrodes; therefore, a traditional approach based on high voltage amplifiers becomes hard to implement. In this paper, we present the process that led to the first irreversible electroporator capable of such performances approved for clinical use. The main design choices and its architecture are outlined. Safety issues are also explained along with the solutions adopted.


Available from: Claudio Bertacchini
Technology in Cancer Research and Treatment
ISSN 1533-0346
Volume 6, Number 4, August 2007
©Adenine Press (2007)
Design of an Irreversible
Electroporation System for Clinical Use
Irreversible electroporation is an ablation modality in which microseconds, high-voltage elec-
trical pulses are applied to induce cell necrosis in a target tissue. To perform irreversible
electroporation it is necessary to use a medical device specically designed for this use.
The design of an irreversible electroporation system is a complex task in which the effec-
tive delivery of high energy pulses and the safety of the patient and operator are equally
important. Pulses of up to 3000 V of amplitude and 50 A of current need to be generated
to irreversibly electroporate a target volume of approximately 50 to 70 cm
with as many
as six separate electrodes; therefore, a traditional approach based on high voltage ampli-
ers becomes hard to implement.
In this paper, we present the process that led to the rst irreversible electroporator capable of
such performances approved for clinical use. The main design choices and its architecture
are outlined. Safety issues are also explained along with the solutions adopted.
Key words Electroporation; Irreversible Electroporation; Ablation Modality; High Voltage
Pulses; Tumor Treatment; Medical Device.
Electroporation is a technique that uses micro to milliseconds electric pulses to
create pores in the cell membrane, thus allowing molecules that, due to their
physical and/or chemical properties, would normally not be able to cross the
cell membrane, to enter the cell (1-5). Electroporation nds applications in
many elds in particular for gene insertion in cells (electrogenetherapy) (6,
7) and for the treatment of cancer (electrochemotherapy). In electrochemo-
therapy, the combination of chemotherapy and electroporation of tumors, the
effects of drugs that usually show little cytotoxicity are greatly increased (8).
The opening of pores in the cell membrane allows the chemotherapeutic agent
to enter the cell at greater, more effective concentration and exert its cytotoxic
action killing the target cell (9-11).
However, if the applied electric eld is above a certain threshold cells are un-
able to seal the pores formed, thus causing cell death due to the loss of homeo-
static mechanisms (11). This phenomenon is termed “irreversible electropora-
tion”. The threshold for irreversible electroporation strongly depends on the
type of tissue under treatment (13).
The main advantage of irreversible electroporation over electrochemotherapy
is the possibility to avoid the use of drugs, as it relies only on the effect of the
Claudio Bertacchini, M.S.*
Pier Mauro Margotti, M.S.
Enrico Bergamini, M.S.
Andrea Lodi, Ph.D.
Mattia Ronchetti, M.S.
Ruggero Cadossi, M.D.
IGEA S.r.l.
Via Parmenide, 10/A
I-41012 Carpi (MO) Italy
Corresponding Author:
Claudio Bertacchini, M.S.
Open Access Article
The authors, the publisher, and the right
holders grant the right to use, reproduce, and
disseminate the work in digital form to all users.
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314 Bertacchini et al.
Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
applied electric eld to kill the cancer cells. However, to
obtain irreversible electroporation of the target tissue, high
voltage pulses need to be generated, the electric eld is
applied by means of electrodes inserted in the tissue to be
treated. Since the amplitude and the gradient of the eld
depend on the applied voltage as well as on the distance be-
tween the electrodes, high values of the electric eld can
be also achieved by arranging the electrodes closer to each
other. However, when treating deep seeded tumors, we de-
sire to introduce the electrodes through the skin both to min-
imize the procedure’s impact and avoid open surgery; thus,
introducing a large number of closely arranged electrodes
to effectively porate the target tissue is not feasible. In this
scenario the goal is to treat a volume of approximately 50
to 70 cm
with up to six electrodes. This requires applied
voltages in the order of 3000 V to obtain irreversible elec-
troporation. The specications of the device ensure that the
electrical eld gradient in a volume 40 cm
is at least 800
V/cm, this is considered to be the threshold for irreversible
electroporation in most cells (13). The electrodes used with
the device are 15 cm long stainless steel needles, partially
insulated, with a diameter of 1 mm. The conductive, non
insulated, distal end of the electrodes can be up to 4 cm long.
The electrodes are inserted under ultrasound guidance.
The high voltages and currents (up to 50 A) used represent
the main problems to be taken into account when designing
a device for irreversible electroporation. Safety issues arise
because of the high energy involved and because of the vari-
able working conditions present in the operating theatre. In
fact, the delivered current depends on the ohmic character-
istics of the tissue under treatment and can differ from point
to point, particularly in the typical heterogeneous tissue that
constitutes tumors. Moreover, the tissue can have its electric
characteristics altered during the treatment, as a consequence
of the deep modications caused to the cells and the extra
cellular environment when high currents are applied.
Consequently in the design of an irreversible electroporator,
one has to keep under control the patient leakage current, to
design a sturdy and fast high voltage pulse generator, with an
high reactivity in case of failure and provide a user-friendly in-
terface for the operators to minimize the chance of user error.
This paper describes the solutions adopted to solve all these
challenging issues in the design and implementation of a
device for irreversible electroporation to be used in the
clinical practice.
General Safety Remarks
In addition to general safety requirements for medical de-
vices stated by regulation and standards (14, 15, 16), specic
safety issues characterize electroporation devices. The prin-
cipal hazards derive from the high energy that is accumulated
on capacitors and from the delivery of high electrical current
to the patient, which involves the risk of electrocution for
both the patient and the operator.
Energy release to the patient must be reliably controlled and
limited: unintended or incorrect release has to be avoided.
Strictly related to this issue is device ruggedness: in the
absence of adequate protective measures, a failure of some
critical component may lead to a complete, unwanted dis-
charge of the accumulated energy.
Reliable energy delivery control characterize the normal de-
vice operation and can be ensured by specic safety mea-
sures implemented in the software/rmware. This goal is
achieved by carrying out risk analysis in the earliest phases
of the device architecture design, in order to identify those
hardware parts that must support software safety features;
ensuring that critical device control is carried out by reliable
programmable systems, and implementing best software/
rmware development practices (17).
Energy delivery limitation refers to fault conditions. It is a
strategic choice: risk control may be obtained either by limit-
ing the probability of a failure, in particular for those critical
components whose failure may lead to uncontrolled energy
delivery to the patient, or by implementing an independent
system that prevents energy delivery above the maximum
normal-condition value; both solutions have pros and cons.
In any case the system must be sufciently rugged to conne
such failure to a remotely likely event.
Ruggedness is intended in particular against short circuits
and sparks that are likely to occur between electrodes due to
the unpredictability of the resistive load of biological tissues,
the presence of conductive solutions and human error.
The likelihood of an electroporation treatment to lead to
electrocution depends on several factors: the applied pulse
voltage, the length of the pulses, the number of pulses, the
pulse repetition rate and, of course, the distance between
the hearth and the electrodes (18). Generally speaking,
synchronization of treatment delivery with the refractory
period of the cardiac cycle is always advisable when there
is not enough condence that the electroporation treatment
cannot determine a current density lower than brillation
threshold of the myocardium.
General Device Structure
The electroporation device is composed of two main parts:
the user interface (UI), that calculates the treatment pa-
rameters based on data inserted by the operator, shows and
elaborates data and signals measured during the treatment,
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Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
Irreversible Electroporation System for Clinical Use 315
and a power unit (PU), which actually generates the pulses
by using the parameters provided by the interface and ac-
quires signals.
The UI is a medical grade PC suitable for use in a operating
room and it guarantees compliance with standards for medi-
cal electrical devices. A standard Operating System (OS) is
used to provide an intuitive graphical user interface, allow-
ing the operator to easily set treatment parameters and to
process measured treatment data. Once the parameters have
been set, the PU should be able to perform the treatment
independently from the non real-time OS and the unpredict-
able delays associated with it. This approach guarantees the
execution of the operations involved in the treatment deliv-
ery with an exact timing sequence and to react immediately
to the events being monitored. The described conguration
allows a ne control over the charge on the capacitors, the
pulse length, the pause between pulses, and to immediately
react to safety-related alarms.
Strict control of timing delays and signals can be better pro-
vided by an FPGA (Field Programmable Gate Array) based
platform than a microcontroller. The FPGA processes the
treatment parameters, controls if the capacitors store enough
energy to deliver a high-voltage, high-current pulse, then
handles the generation of pulses and the measurement of
the delivered treatment.
A schematic representation of an electroporator device is
shown in Figure 1. The PU is composed of high energy parts
(highlighted in gray in Figure 1) and a digital control part.
The control block mainly includes the FPGA and an interface
for communicating with the UI that directly supervises and
handles the operations of the other blocks. The high voltage
capacitors store all the energy for a sequence of pulses with
the desired voltage, as commanded by the FPGA. Once the
capacitors have charged, the FPGA waits for a signal to pro-
ceed with the treatment. The signal is provided directly by the
operator by means of a double pedal with IPX-8 degree of pro-
tection from liquids (as imposed by the standards for the use in
operating theatres). The rst pedal is used by the operator to
enable the second pedal that actually starts the treatment.
Once triggered, the FPGA is in charge of two main tasks: it
controls the output pulse block and acquires the measure of
voltage and current actually delivered to the patient through
the electrodes. The pulse length can be suitably controlled
by using two high voltage IGBT (Insulated Gate Bipolar
Transistor): one to control the pulse length and the second
dedicated to avoid the delivery of uncontrolled pulses under
failure conditions.
The electroporator device is able to use up to six electrodes
to apply an electric eld with the most appropriate shape and
intensity to homogenously cover the target tissue. A switch-
ing block is needed to route the treatment to the electrodes
in sequenced fashion. In order to implement such capabil-
ity, high voltage SPDT (Single Pole Double Throw) relays
are used. For each electrode two relays are involved: one to
select the polarity of the pulse and the second to connect the
electrode. The second relay also has the additional purpose
of performing an initial test of the device efciency conduct-
ed using an internal resistive load.
Finally, the FPGA directly controls the switching activity of
the relays of the switching block by connecting each elec-
trode in turn to the output pulse generation block.
In order to reduce design complexity, we chose to consider
the whole PU as the patient circuit, dened as any electrical
circuit containing conductive parts, which are not insulated
from the patient (16). This means that for sake of safety
not only the high voltage part is completely insulated from
ground but the whole PU. Based on the standards we found
that the insulation required is 7500 V; therefore, we provid-
ed the PU with a transformer having an internal insulation
of more than 8000 V.
Since the PC-based user interface is referred to ground and
communicates with the power unit via USB (Universal Stan-
dard Bus), it is necessary to isolate the USB connection. To
this end, we adopted an optically insulated USB cable.
User Interface
Power Unit Control
Pedal Trigger
Output pulse
generation and
High Voltage
capacitor charge
Electrode switching
Figure 1: Chart of the main blocks composing the device. The power unit
is composed of high energy parts, highlighted in gray, and a digital control
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Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
Design Issues
Based on the general structure shown, we implemented an
irreversible electroporation device capable of charging the
capacitors up to 3500 V and to sustain a current drawn by
the tissues of up to 50 A. Many issues have raised during the
design process mainly because of the high energy involved
and because of the need for safety associated with a medical
device to be used in the operating room. The following para-
graphs provide a hint on the solutions we adopted.
Pulse Generation
Ideally, the delivered pulses should be square ones. Unfor-
tunately, the generation of square pulses at 3000 V is very
expensive and difcult to achieve, as it requires the design of
a very-high-voltage amplier. We investigated two different
approaches for the generation of pulses that approximate the
ideal square shape, without requiring the use of an amplier:
the pulse transformer and the high voltage generator.
Pulse Transformer: When using a pulse transformer,
pulses at lower voltage are applied to the primary coil of
a step-up pulse transformer, which generates the required
high voltage pulses on the secondary coil. The energy re-
quired is supplied by the charge stored on capacitors. The
output energy to be delivered is stored on capacitors con-
nected in parallel to reach the desired capacity. The value
of the required maximum charged voltage on the capacitors
is dependent on the transformer ratio.
Since the pulse transformer is less efcient at low frequen-
cies than at higher frequencies, a bigger transformer is re-
quired to generate longer pulses. Another issue with the use
of a transformer is the major difference between the achieved
pulse shape and the ideal square one, especially in presence
of low-resistance loads.
Tests have been carried out using a toroidal pulse transformer
having 148 mm outer diameter; 56 mm height; 3.8 kg weight.
The outcome was that the pulse transformer did not allow
pulses longer than 30 μs and pulse repetition frequency had
to be lower than 81 Hz (1/12300 μs). Figure 2 shows the
Figure 2: Two Pulses at 3000 V, 30 μs long, 30 μs pause, with a 500 Ω load.
Figure 3: Pulse voltage (green) and current (blue) dependence from load
with a 3000 V nominal amplitude, 30 μs long pulse: (a) 500 Ω, (b) 250
Ω, (c) 60 Ω.
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Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
Irreversible Electroporation System for Clinical Use 317
effect of transformers core saturation that occurs at higher
pulse repetition frequencies.
The load effect became signicant with loads lower than 250
Ω, as shown in Figure 3: as load impedance decreases, the volt-
age pulse amplitude on the secondary coil of the transformer
becomes signicantly lower, the pulse shape is also affected.
High Voltage Generator: When using a high voltage gen-
erator the capacitors are directly connected to the load by
means of switches in order to generate the pulses. With this
approach the ideal square pulses are approximated to a time-
controlled free discharge of a capacitor (see Figure 4).
The quality of this approximation depends on the load. This
means that such kind of pulse could be well approximated to a
square pulse only if the current drawn by the load is low. This
is because the current owing on the load discharges the ca-
pacitors, thus causing the amplitude loss shown in Figure 4. A
small discharge current causes a little drop and the amplitude
at the end of the pulse is only slightly lower than the initial
capacitor voltage. On the other hand if the load has a particu-
larly low resistance it will draw high current, and the pulse
shape will have a considerable drop, although starting from
the required voltage. The capacitor should be dimensioned so
that the time constant of the voltage decay is much longer than
pulse duration also in the least favorable load conditions.
The high voltage generator approach requires a high voltage
power supply that charges the capacitor at the desired initial
pulse voltage and high voltage capacitor of sufcient capaci-
tance. The required high voltage may be obtained connecting
capacitors in series, in spite of the total capacitance, which re-
sults in a fraction of the capacitance of each single capacitor.
In order to generate the pulses a high voltage Mosfet switch
or IGBT can be used to connect the load with the capacitors
only for the required time of the pulse length.
After some evaluation about dimensions, costs and consider-
ing the specications, the high voltage generator approach
generally has shown to be the best solution.
Amplitude loss
Initial Amplitude
Pulse Length
Figure 4: Truncated slow-decay exponential. The square wave pulse is
produced by a partial discharge of a large capacitor, which requires the inter-
ruption of high currents against high voltages.
Figure 5: Voltage and Current wave forms at 3000 V (at the end of ten 100 μs, 20 μs spaced pulses) on a 68 Ω load (approx. 50 A peak current), obtained using
the high voltage generator approach. A single pulse sequence in (a). The repetition of 8 sequences in (b). The dwell between sequences is not shown.
Figure 6: Trolley containing the high
voltage power unit at the bottom and
the PC with the user interface (key-
board, touchpad, and display) on top.
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Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
Speed Issue
Another main issue is the device responsiveness. The puls-
es delivered can have a length between 20 μs and 1 ms and
require a fast control mechanism. Due to the frequency of
the pulses and the high currents involved, we found that a
safety protection using fuses is not reliable enough, since it
is hardly possible to have fuses with a reaction time of few
microseconds. For this reason we decided to implement a
dedicated fast redundant hardware solutions to protect both
the device and the patient.
Variable Load
A peculiarity of the electroporation process is that the resis-
tive load of a biological tissue varies greatly and is, therefore,
unknown at the time of treatment. Moreover, the resistance
depends on the physical properties of the electrodes used and
there is a decrease of the resistance during the treatment due to
the changes induced by the electrical eld in the target tissue.
As a consequence, it is almost impossible to make an accurate
prediction of the load without a preliminary test and it is safer
to consider the least favorable scenario. For this reason we
designed the device considering the event of sparks and short
circuits and introduced a current limitation to avoid injuries to
the patient and failure of the device. Simulations allowed to
estimate that in the worse non-short-circuit condition, the load
should not draw more than 50 A; therefore, it is assumed that if
during the treatment the drawn current exceeds this threshold, it
is probably due to a short circuit or spark occurring at the elec-
trodes. In this case the device interrupts the pulse sequence.
Size Issue
The size of the device can vary depending on the choices
made during the design phase. We chose to build a device
provided with a trolley (Figure 6), allowing us to have larger
space for the electronics. The advantages of this choice are:
the required electrical insulation is achieved more easily and
it is possible to increase the robustness to noise induced by
the high voltage parts. We decided to put the PC for the UI
into a separate part close to the LCD display and the key-
board. The PU is located at the bottom of the trolley.
Software Architecture
As shown in the device structure, a double level of control is
desirable. The software consists of two main parts that in-
teract with each other but are logically and functionally inde-
pendent: a high level part implements the software graphical
user interface and a low level control, implemented in hard-
ware and in the FPGA rmware, that is responsible for all
functions that directly control the power part of the device.
The Graphical User Interface
The Graphical User Interface (GUI) was developed thinking
of ease of use and enable also an inexperienced user to focus
on the therapy rather than on the device usage.
The main structure of the GUI is a typical wizard applica-
tion with the ‘next’ and ‘back’ buttons that allow navigation
between pages.
The inner task of the GUI is to monitor the status of the PU at
xed time intervals and display the main information regard-
ing the capacitors charge and the treatment delivery process.
The GUI is based on the following structure:
COMM_LAYER: a layer that performs the basic
communication with the power device, supervises
the USB communication, and performs basic read/
write operations;
CHECK_LAYER: checks the input data inserted by
the operator to prevent loading of inconsistent pa-
rameters on the power unit;
TRANSLATION_LAYER: elaborates all data re-
ceived from the power unit in a format such that
the user can quickly analyze the information on the
treatment delivered.
the background at all times during the treatment delivery and
ensure a strict timing synchronization of the different tasks
and between the GUI and PU control rmware. This fea-
ture is implemented by means of a handshake protocol that
enables the operator to have full monitoring of the ongoing
operations. In this way a treatment can be aborted by the op-
erator at any time via software and both the PU and the GUI
return in a safe state, waiting for new inputs. On the other
hand, if an error occurs during an operation, the GUI immedi-
ately noties it to the user who can decide how to proceed.
In order to improve safety in the use of this device, tests are
performed at start-up before the GUI actually starts operat-
ing. These tests check the main functionality of the device
such as a live communication between UI and PU, the cor-
rect rmware version on the power unit, complete check
of the RAM chips of the PU control hardware, a complete
charge and discharge cycle of the capacitors, a test on inter-
nal test loads, et cetera.
Power Unit Control
A FPGA has been chosen to control the whole PU. By using
a dedicated board we allow the PC-based UI to represent the
FPGA as a series of addresses where the treatment param-
eters are stored. The FPGA rmware has the structure shown
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Technology in Cancer Research & Treatment, Volume 6, Number 4, August 2007
Irreversible Electroporation System for Clinical Use 319
in Figure 7 and it is divided into several parts, each one with
a well dened task. The main parts are: the interface block
used to communicate with the PC; the charge control part to
handle the charge of the capacitors; the generation part to
control the pulse generation; the measurement part to allow
the measure of voltage and current during the treatment, and
the switching part to control the relay congurations.
The system controls the pulses by means of two high volt-
age IGBTs. These two components have different purpos-
es: the rst is directly driven by the FPGA to determine the
desired pulse length, and the second IGBT is used to limit
the maximum length of each pulse to 1ms, for safety rea-
sons in the event of failure. Since the specications allow
a maximum current of 50 A, we used the IGBTs to control
the current as well. We improved a standard driver with
a circuit capable of readily reacting to an over-current, by
causing the pulse to stop within 10 to 20 μs.
Since both the capacitor voltage and the current and volt-
age of the pulses are not required to be measured at a high
rate, the use of analogue-to-digital converters with a serial
interface has been preferred. In this way, a compact SPI (Se-
rial Peripheral Interface) communication system can be used
between the measure blocks and the FPGA.
The charging of the capacitors is operated by a high voltage
generator with a maximum voltage over 3500 V. The charge
control block enables the generator when a charge phase is
required and disables it both during the pulse delivery and
during any discharge process. Furthermore, the charge con-
trol block checks if the generator is working properly: when
the expected voltage cannot be reached the FPGA sends an
alarm message to the UI and puts the system into a safe con-
dition by immediately closing a relay that discharges the ca-
pacitors on an internal load. For safety reasons the system
has always the internal load connected and only when the
treatment is in progress it re-connects the output section.
To improve the efciency of the pulse and generation control
we chose to use two different clock domains: one reserved
only for the communication section that uses a 30 MHz
clock from the microprocessor used to implement the USB
communication; the second clock domain, that controls the
charge, the pulse generation, and measurement sections uses
a separate 20 MHz clock. With this solution we ensure that
even if the microprocessor fails, the system will complete the
treatment correctly and afterwards will reach a safe state.
In consideration of a possible application of the treatment
close to the heart we improved the safety of the device by
introducing the capability to synchronize pulse delivery with
an external ECG device so that the treatment is delivered
only during the refractory period.
Regulation and Standards
Compliance with regulation and standards guarantees that
the device meets electrical safety requirements.
Since the irreversible electroporation system is a medical de-
vice, we followed European standards EN60601-1 (14) and
EN60601-2 (15), and the harmonized UL standard UL60601
(16) during the whole design process. Due to the high volt-
ages involved in the use of the device, we decided to also fol-
low other standards, like the one for debrillators (19), and
the one for high frequency surgical equipment (20).
The development of an irreversible electroporation system
approved for the use in the clinical practice, allows a novel
approach to tissue ablation. Tumor ablation based on ir-
reversible electroporation relies solely on the application
of an intense enough electric eld to the target tissue to
cause cell death. The device has been developed to allow
the use of up to six independent electrodes. The electrodes
are not restricted to a xed geometry, rather they can be in-
dependently positioned based on the tumor size, shape, and
position, to ensure that the target is entirely enclosed within
the applied electric eld, thus ensuring complete tissue ab-
lation. The result of the development process is a reliable,
safe, and high performing medical device for irreversible
electroporation based tissue ablation.
Figure 7: FPGA rmware architecture.
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Received: April 13, 2007; Revised: June 22, 2007;
Accepted: June 26, 2007
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    • "Initially, the occurrence of IRE during reversible electroporation procedures was considered an unwanted side effect . However, the ability of IRE to induced selective cell death turned IRE into a tumour ablation modality, leading to the development of the commercially available Nanoknife™ (AngioDynamics, Queensbury, New York) [12]. Histopathological outcomes after IRE show a sharp demarcation between ablated and non-ablated tissue, whereas thermal ablation techniques show a transitional zone of partially damaged tissue due to insufficient temperatures for definitive ablation [14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life. Methods/Design: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires. Discussion: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE. Trial registration: database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.
    Full-text · Article · Dec 2016 · BMC Cancer
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    • "As it can be observed inFigure 6A similar trend of current was also acquired by calculation of an absolute value of electric current density. It should be noted that the highest obtained value of electric current in this study was around 5.5 A while in clinical cases of in vivo IRE the current can reach up to 50 A [26] due to electrode depth of insertion. Application of CDI during in vivo IRE would therefore enable measurement of current density distributions with even better SNR than one presented in this study. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Electroporation is gaining its importance in everyday clinical practice of cancer treatment. For its success it is extremely important that coverage of the target tissue, i.e. treated tumor, with electric field is within the specified range. Therefore, an efficient tool for the electric field monitoring in the tumor during delivery of electroporation pulses is needed. The electric field can be reconstructed by the magnetic resonance electric impedance tomography method from current density distribution data. In this study, the use of current density imaging with MRI for monitoring current density distribution during delivery of irreversible electroporation pulses was demonstrated. Methods Using a modified single-shot RARE sequence, where four 3000 V and 100 μs long pulses were included at the start, current distribution between a pair of electrodes inserted in a liver tissue sample was imaged. Two repetitions of the sequence with phases of refocusing radiofrequency pulses 90° apart were needed to acquire one current density image. For each sample in total 45 current density images were acquired to follow a standard protocol for irreversible electroporation where 90 electric pulses are delivered at 1 Hz. Results Acquired current density images showed that the current density in the middle of the sample increased from first to last electric pulses by 60%, i.e. from 8 kA/m2 to 13 kA/m2 and that direction of the current path did not change with repeated electric pulses significantly. Conclusions The presented single-shot RARE-based current density imaging sequence was used successfully to image current distribution during delivery of short high-voltage electric pulses. The method has a potential to enable monitoring of tumor coverage by electric field during irreversible electroporation tissue ablation.
    Full-text · Article · Aug 2015 · BioMedical Engineering OnLine
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    • "It relies on nonthermal tissue ablation resulting from irreversible electroporation [89]. Manufactured by Angiodynamics USA, it uses a pulse generator capable of delivering 10 to 100 pulses up to 3,000 V at 50 A through pairs of long needle electrodes [64]. Based on free discharge of capacitors, it is simple and efficient and does not require a HV amplifier. "
    [Show abstract] [Hide abstract] ABSTRACT: As described in Part 1, a cell membrane can be made permeable to various molecules by carrying out a procedure called electroporation [1]. This procedure is being successfully used in biology, biotechnology, and medicine [2], [3]. It requires electroporators and electrodes. An electroporator generates short HV pulses of specific shape, amplitude, duration, number, and repetition frequency [4], and the pulses are applied to the target cells or load through the electrodes [5]. The energy delivered to the load is governed by the number of pulses and the pulse voltage, current, and duration. In biomedical applications that energy can be several joules; in biotechnology, where electroporation is used for treatment of agricultural products and water, it can be several kilojoules.
    Full-text · Article · May 2014 · IEEE Electrical Insulation Magazine
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