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Targeted Drug Delivery Using Ultrasound Beam Focusing & LabVIEW

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Original Authors: Dave Lines, Diagnostic Sonar Ltd

Edited by Cyth Systems

Drug delivery system.
Drug delivery system.

The Challenge

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

The Solution

Using the NI PXI 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 optimization by advanced phase aberration correction.

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.

Left: Using PXI for Ultrasound Array Driving System, Right: 3D Representation of Normalized Ultrasonic Crossbeam Pattern at Array’s Focal Distance

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 localized 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.

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.

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.

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.

Original Authors:

Dave Lines, Diagnostic Sonar Ltd

Edited by Cyth Systems


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