Researching Future Targeted Drug Delivery Techniques with Ultrasound Beam Focusing Using FlexRIO and LabVIEW

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"The combination of LabVIEW and FlexRIO delivered all of the power and flexibility of a custom-made multichannel ultrasound system, but within a fraction of the time and at a significantly reduced cost."

- Dave Lines, Diagnostic Sonar Ltd

The Challenge:
Driving and optimising a bespoke multielement ultrasound phased array with continuous wave signals for therapeutic applications such as targeted drug delivery (TDD).

The Solution:
Using the powerful FlexRIO platform to build a modular, ultrasonic beam-focusing system to deliver continuous wave (CW) pulse-width modulated signals to a custom multichannel transmitter. The resulting system provided individual ultrasound array element control, tightly focusing and steering the ultrasound beam for optimisation by advanced phase aberration correction.

Author(s):
Dave Lines - Diagnostic Sonar Ltd
Zhen Qiu - Institute for Medical Science and Technology, University of Dundee
Rod Habeshaw - University of Dundee
Muhammad Sadiq - University of Dundee
Sandy Cochran - University of Dundee

The Team

The Institute for Medical Science and Technology (IMSaT), University of Dundee, is an interdisciplinary institute for future medical technologies that brings engineers, physicists, and life scientists together with clinicians and health service providers. Among its many research themes, medical ultrasound technology is important for both diagnostic and therapeutic applications.

Diagnostic Sonar Ltd. (DSL), founded in 1975, developed the first real-time medical ultrasound scanner manufactured in the UK. Over the following four decades, the company expanded into other areas, including non-destructive testing (NDT), magnetic resonance imaging test samples (phantom) for verifying medical scanners and, more recently, ultrasound array controllers based on NI PXI hardware.

Ultrasonic Targeted Drug Delivery

Unlike conventional drug administration, where medicines are absorbed across entire biological membranes, targeted drug delivery (TDD) seeks to increase the concentration of the medication in specific areas for prolonged and highly localised drug interactions with diseased tissue. This targeted approach to drug administration offers many advantages, including reduced side effects, decreased fluctuation in circulating drug levels, and a more predictable, uniform effect of the drug at the treatment site.

In TDD, ultrasound-induced temperature increases and cavitation can either increase the permeability of biological membranes, or trigger the drug carriers, such as liposomes, which are sensitive to elevated temperature and pressure, to release the drug only in the tissue volume targeted by the focused ultrasound. Therefore, focusing ultrasonic energy into small, well-defined volumes is crucial to targeted drug delivery, where high focusing-gain and low side-lobe response are required.

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Figure 1. Focused Ultrasound Energy is Enough to Rotate Grouped Objects

 

Technicians can electronically focus and steer an ultrasound beam within a patient’s body by applying appropriate phase and amplitude control over the excitation signal to each individual transmitter array element. In practice, defocusing is unavoidable, caused by either residual aberration from the device itself or signal distortion as the ultrasonic signals propagate through a patient. The ability to correct phase aberration is thus a necessity in the ultrasound driving system.

Many multichannel ultrasound array-driving systems have been designed for either medical imaging or NDT, where repeated pulses with high voltage but short pulse length are generated. Conversely, therapeutic ultrasound applications require driving signals in CW or long burst modes, with higher power and longer sonication periods.

Traditionally, driving such multielement array transducers in a laboratory environment has required a huge range of discrete function generators, physical output switches, and power amplifiers, which can be expensive and cumbersome. To accelerate our important ultrasonic TDD research, which represents the future of medication delivery, we required a flexible, cost-effective and portable experimental multichannel driving system.

System Description

For this project, DSL designed and built the FI Toolbox, the system that drives ultrasonic arrays. It is based on a 32-channel transmitting card (DSL32T); a 32-channel receiving card (DSL32R); and a single 32-channel NI 5752 digitizer, interfacing with two PXI-mounted FlexRIO PXIe-7966 field programmable gate array (FPGA) devices, controlled with LabVIEW and LabVIEW FPGA from a host computer. The system generates 70% pulse-width modulated square (PWM) waves to deliver signals to each channel. With three-level wave shaping, the square waves can be used to define an approximate sine wave, which significantly reduces the third harmonic content in the signal, resulting in more accurate ultrasound beam shaping.

Many of the technologies in our TDD system were originally devised for NDT applications, where ultrasonic signals are used to verify material or component properties without causing damage. However, to ensure that our system met the strict TDD requirements for CW operation, it was modified with an active cooling system. The phase of the signals used to drive the ultrasonic elements is controlled and adjusted in 11.25 o increments for each channel, over the range of 0 o ≤ θ < 360 o. In its CW configuration, the DSL transmitter can offer a maximum ±30 V input signal to 32 channels without exceeding the power dissipation of the various components.

 

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Figure 2. Ultrasound Array Driving System       

 

Phase Aberration Correction Experiment

IMSaT at the School of Medicine, University of Dundee, under a programme managed by the Scottish Universities Physics Alliance, built a bespoke ultrasound array, working at approximately 1 MHz. The array has a faceted spherical shape inspired by a geodesic dome and consists of 24 triangular piezoelectric-polymer composite plates that are further diced into 96 elements. For the present work, the array elements were grouped in sets of three into 32 channels in a 2D segmented annular configuration, to match the FI Toolbox instrumentation channel count.

Using a hydrophone-based correction mechanism, the phase delay to each channel was modified to overcome the residual aberration caused by minor geometric positioning errors, thereby creating a clear, tight focus for the ultrasonic beams, shown in Figure 4. By correcting for phase aberration, we managed to boost peak voltage at the focal point by 4X.

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Figure 3. Normalized Crossbeam Pattern at Array’s Focal Distance Before Phase Aberration Correction

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Figure 4. Normalized Crossbeam Pattern at Array’s Focal Distance After Phase Aberration Correction

 

Once we had corrected for aberrations and boosted beam intensity, we were able to undertake our sonic screwdriver experiment, where we explored moving the ultrasonic focal point to follow a circular path with a 2.5 mm radius in its geometrical focal plane. With 10 degrees as the increment, the focus moved 36 steps to complete a circle. The aberration-corrected radiation force generated by the focused ultrasound beams was enough to rotate relatively large floating objects.

 

 

With  the aid of the DSL system, the secondary lobes were measured to be lower than -12 dB, well below the widely accepted level of -10 dB for focused ultrasound therapeutic applications. 

For our application, the FlexRIO hardware provides a compact, modular system to drive electronics for ultrasound arrays. The combination of LabVIEW and FlexRIO delivered all of the power and flexibility of a custom-made multichannel ultrasound system, but within a fraction of the time and at a significantly reduced cost. Additionally, thanks to the flexibility of LabVIEW, our team of scientific and clinical researchers easily customized the system down to the hardware.

Preliminary results have shown a prototyping path for connecting custom ultrasound arrays to a commercial driving system based on NI and DSL technologies. We have accurately focused the ultrasound beam, clearly defining the treatment area in clinical practice. The continuous wave excitation resulting from our modification to both software and hardware has also increased the output power, evident in our manipulation of small objects with the ultrasound beam.

The Future of Our Research

The current DSL FI Toolbox system configuration is suitable for mid-power therapeutic applications, where overall power is limited by the maximum heat dissipation of the transmission board. By stacking multiple transmitters in parallel, we can multiply power delivered to the array accordingly. 

In our future plans, adding two more DSL32T and NI 7966 FlexRIO devices to the system will allow us to drive all 96 elements of the array individually, significantly boosting output power levels. This means the same technology can be used to research focused ultrasound surgery, where highly focused ultrasonic energy can treat diseased tissue with thermal ablation or mechanical cavitation. One of the major benefits of the NI software-defined approach to instrumentation is that repurposing laboratory equipment for future experiments is simple and cost-effective.

Acknowledgement

The work was sponsored by the Scottish Universities Physics Alliance (SUPA).

 

Author Information:
Dave Lines
Diagnostic Sonar Ltd

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