Ultrasound-based functionalized biopsy markers for lesion tracking through neoadjuvant systemic therapy

Cario, Jenna

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https://hdl.handle.net/2142/129460 Copy

Description

Title

Ultrasound-based functionalized biopsy markers for lesion tracking through neoadjuvant systemic therapy

Author(s)

Cario, Jenna

Issue Date

2025-04-28

Director of Research (if dissertation) or Advisor (if thesis)

Oelze, Michael L

Doctoral Committee Chair(s)

Oelze, Michael L

Committee Member(s)

• Kumar, Rakesh
• Banerjee, Arijit
• Lee, Christine U

Department of Study

Electrical & Computer Eng

Discipline

Electrical & Computer Engr

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• ultrasound
• radiological clips
• breast biopsy markers
• neoadjuvant systemic therapy
• electronic clip

Abstract

As part of the standard care for breast cancer patients undergoing neoadjuvant systemic therapies (NST), a small biopsy marker, or clip, is inserted into or near the area being targeted for treatment. This strategy allows treated areas to be located more consistently after NST, despite any resulting morphological changes, than if no markers were used. However, challenges remain with the use of ultrasound to image these markers. Medical imaging applications, such as those used in a clinic or during surgery, demand consistency and reliability in a variety of environments and adverse conditions. Versatility and robustness of design are tantamount, which applies to both the markers themselves and the signals they return. Ultrasound is a highly attractive option in environments where real-time visualization of the body habitus is needed, such as during clip placement guidance and preoperative localization. It is a clinical mainstay and among the most common imaging modalities. It does not use ionizing radiation as X-ray or computed tomography (CT) scans do, and systems are portable and low-cost to acquire and maintain. Patients can be imaged at bedside, and there are no material compatibility concerns as exist with magnetic substances and magnetic resonance imaging (MRI) machines. Ultrasound probes consist of small piezoelectric elements that store electrical voltage as tension in their crystal lattice structures, and release this tension as high-frequency mechanical vibrations. Conversely, mechanical vibrations incident on the elements induce an electrical voltage. In this way, an acoustic pulse can be sent out from these elements, bounce off of structures in range of the pulse, and be received as echoes whose intensity directly correlates to a voltage magnitude. One of the most common configurations for clinical ultrasound probes is an array of uniform piezoelectric elements arranged in a single line, where the dimensions of the elements themselves will influence image width and lateral resolution. Ultrasound images tend to be leveraged in a qualitative manner, and radiofrequency (RF) data on the returned acoustic echoes in the imaged area must be beamformed to reconstruct an image that can be evaluated by a human observer. A beamformed ultrasound image is a compression of underlying numerical data, which can contain visually imperceptible patterns. In quantitative ultrasound (QUS), RF data is processed with numerical and statistical learning methods in order to ascertain information about the imaged environment that is not visible in an ultrasound image. QUS data can reveal structures associated with disease or malignancy even in the absence of visual indicators. We are currently evaluating QUS as a technique to identify early the response of breast cancer to NST. To use QUS, calibration is needed with a reference material in order to compensate for effects inherent to a given imaging system and settings. Doing so isolates the aspects of the numerical data that are inherent to the imaged medium from those inherent to the imaging system, and provides a method of standardizing measurements across multiple setups, systems, and institutions. One point of focus in this thesis is the evaluation of a spherical titanium bead that can act both as an in situ calibration target and a biopsy clip or marker. Using a reference which is adjacent to and at the same depth as an area of interest means the calibration and target experience very similar overlying conditions. This further isolates properties of interest, such as scattering, from other tissue effects such as attenuation. In a simple imaging environment with a spherical calibration target, the interplay of subtle positional shifts against physical probe limitations such as array element spacing can complicate the efficient recovery of a consistent signal, which is a requirement for accurate QUS measurements. Even without considering the restrictions that must be imposed in order to obtain accurate QUS estimates, ultrasound probe orientation and position relative to a small target such as a biopsy marker play an outsized role in successful visualization. Commercial off-the-shelf marker designs come in many non-spherical shapes designed to fit within a biopsy needle barrel for ease of deployment and patient comfort. These asymmetries create even greater variability in conspicuity relative to imaging orientation, which can complicate successful localization. Exploring how positioning affects these commercially-available clips is another feature point in this thesis, and significant differences in conspicuity with respect to viewing angle arise. This leads to a consideration of how electronics engineering may be used in order to improve ultrasonic clip conspicuity over what is achievable with passive marker design. By making the markers into active electronic devices, which transmit a specialized acoustic signal back to the imaging probe, we can decouple the clip response from the magnitude of the pulse used to image and potentially also from the orientation of the probe relative to the clip. So long as the imaging pulse is strong enough to activate the marker, the clip can send out a signal that encodes information such as an identification number or sensor readout. The signal will have its own inherent visibility in an ultrasound image, increasing the likelihood of successful localization. Any test platform designed to prototype such a device should capture as many of the design requirements for the final hardware, communication channel, and received signal processing as possible. Power, timing, and size considerations, as well as processing capability of the imaging system and the desire to obtain real-time results, introduce engineering tradeoffs in all parts of the system. These design challenges are explored primarily through experiment where possible, and steps to propagate the design through later stages into clinical translation are provided. This thesis outlines multiple strategies for increasing the functionality of radiological clips by leveraging already-common imaging equipment. It ultimately presents an electronic system, a signal design, and the corresponding processing that can meet or be readily adapted to enable communication with an ultrasound imaging system from an implanted device. With the design principles proposed herein, a standalone electronic clip design can progress toward a scale prototype.

Graduation Semester

2025-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129460

Copyright and License Information

Copyright 2025 Jenna Cario

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