Piezoelectric needle sensor reveals mechanical heterogeneity in human thyroid tissue lesions.

Palpable thyroid lesions are common, and although mostly benign, lethal malignant nodules do occur and may be difficult to differentiate. Here, we introduce the use of a piezoelectric system called Smart-touch fine needle (or STFN) mounted directly onto conventional biopsy needles, to evaluate abnormal tissues, through quantitative real-time measurements of variations in tissue stiffness as the needle penetrates tissue. Using well-characterized biomaterials of known stiffness and explanted animal tissue models, we first established experimental protocols for STFN measures on biological tissues, as well as optimized device design for high signal-to-noise ratio. Freshly excised patient thyroids with varying fibrotic and malignant potential revealed discrete variations in STFN based tissue stiffness/stiffness heterogeneity and correlated well with final histopathology. Our piezoelectric needle sensor reveals mechanical heterogeneity in thyroid tissue lesions and provides a foundation for the design of hand-held tools for the rapid, mechano-profiling of malignant lesions in vivo while performing fine needle aspiration (FNA)

New Mechatronic Systems for the Diagnosis and Treatment of Cancer

Both two dimensional (2D) and three dimensional (3D) imaging modalities are useful tools for viewing the internal anatomy. Three dimensional imaging techniques are required for accurate targeting of needles. This improves the efficiency and control over the intervention as the high temporal resolution of medical images can be used to validate the location of needle and target in real time. Relying on imaging alone, however, means the intervention is still operator dependent because of the difficulty of controlling the location of the needle within the image. The objective of this thesis is to improve the accuracy and repeatability of needle-based interventions over conventional techniques: both manual and automated techniques. This includes increasing the accuracy and repeatability of these procedures in order to minimize the invasiveness of the procedure. In this thesis, I propose that by combining the remote center of motion concept using spherical linkage components into a passive or semi-automated device, the physician will have a useful tracking and guidance system at their disposal in a package, which is less threatening than a robot to both the patient and physician. This design concept offers both the manipulative transparency of a freehand system, and tremor reduction through scaling currently offered in automated systems. In addressing each objective of this thesis, a number of novel mechanical designs incorporating an remote center of motion architecture with varying degrees of freedom have been presented. Each of these designs can be deployed in a variety of imaging modalities and clinical applications, ranging from preclinical to human interventions, with an accuracy of control in the millimeter to sub-millimeter range

Biomechanical modelling of probe to tissue interaction during ultrasound scanning

Purpose: Biomechanical simulation of anatomical deformations caused by ultrasound probe pressure is of outstanding importance for several applications, from the testing of robotic acquisition systems to multi-modal image fusion and development of ultrasound training platforms. Different approaches can be exploited for modelling the probe-tissue interaction, each achieving different trade-offs among accuracy, computation time and stability. Methods: We assess the performances of different strategies based on the finite element method for modelling the interaction between the rigid probe and soft tissues. Probe\u2013tissue contact is modelled using (i) penalty forces, (ii) constraint forces, and (iii) by prescribing the displacement of the mesh surface nodes. These methods are tested in the challenging context of ultrasound scanning of the breast, an organ undergoing large nonlinear deformations during the procedure. Results: The obtained results are evaluated against those of a non-physically based method. While all methods achieve similar accuracy, performance in terms of stability and speed shows high variability, especially for those methods modelling the contacts explicitly. Overall, prescribing surface displacements is the approach with best performances, but it requires prior knowledge of the contact area and probe trajectory. Conclusions: In this work, we present different strategies for modelling probe\u2013tissue interaction, each able to achieve different compromises among accuracy, speed and stability. The choice of the preferred approach highly depends on the requirements of the specific clinical application. Since the presented methodologies can be applied to describe general tool\u2013tissue interactions, this work can be seen as a reference for researchers seeking the most appropriate strategy to model anatomical deformation induced by the interaction with medical tools

Novel Ultrasound Elastography Imaging System for Breast Cancer Assessment

Abstract Most conventional methods of breast cancer screening such as X-ray, Ultrasound (US) and MRI have some issues ranging from weaknesses associated with tumour detection or classification to high cost or excessive time of image acquisition and reconstruction. Elastography is a non- invasive technique to visualize suspicious areas in soft tissues such as the breast, prostate and myocardium using tissue stiffness as image contrast mechanism. In this study, a breast Elastography system based on US imaging is proposed. This technique is fast, expected to be cost effective and more sensitive and specific compared to conventional US imaging. Unlike current Elastography techniques that image relative elastic modulus, this technique is capable of imaging absolute Young\u27s modulus (YM). In this technique, tissue displacements and surface forces used to mechanically stimulate the tissue are acquired and used as input to reconstruct the tissue YM distribution. For displacements acquisition, two techniques were used in this research: 1) a modified optical flow technique, which estimates the displacement of each node from US pre- and post-compression images and 2) Radio Frequency (RF) signal cross-correlation technique. In the former, displacements are calculated in 2 dimensions whereas in the latter, displacements are calculated in the US axial direction only. For improving the quality of elastography images, surface force data was used to calculate the stress distribution throughout the organ of interest by using an analytical model and a statistical numerical model. For force data acquisition, a system was developed in which load cells are used to measure forces on the surface of the breast. These forces are input into the stress distribution models to estimate the tissue stress distribution. By combining the stress field with the strain field calculated from the acquired displacements using Hooke\u27s law, the YM can be reconstructed efficiently. To validate the proposed technique, numerical and tissue mimicking phantom studies were conducted. For the numerical phantom study, a 3D breast-shape phantom was created with synthetic US pre- and post-compression images where the results showed the feasibility of reconstructing the absolute value of YM of tumour and background. In the tissue mimicking study, a block shape gelatine- agar phantom was constructed with a cylindrical inclusion. Results obtained from this study also indicated reasonably accurate reconstruction of the YM. The quality of the obtained elasticity images shows that image quality is improved by incorporating the adapted stress calculation techniques. Furthermore, the proposed elastography system is reasonably fast and can be potentially used in real-time clinical applications

Development and Validation of Mechatronic Systems for Image-Guided Needle Interventions and Point-of-Care Breast Cancer Screening with Ultrasound (2D and 3D) and Positron Emission Mammography

The successful intervention of breast cancer relies on effective early detection and definitive diagnosis. While conventional screening mammography has substantially reduced breast cancer-related mortalities, substantial challenges persist in women with dense breasts. Additionally, complex interrelated risk factors and healthcare disparities contribute to breast cancer-related inequities, which restrict accessibility, impose cost constraints, and reduce inclusivity to high-quality healthcare. These limitations predominantly stem from the inadequate sensitivity and clinical utility of currently available approaches in increased-risk populations, including those with dense breasts, underserved and vulnerable populations. This PhD dissertation aims to describe the development and validation of alternative, cost-effective, robust, and high-resolution systems for point-of-care (POC) breast cancer screening and image-guided needle interventions. Specifically, 2D and 3D ultrasound (US) and positron emission mammography (PEM) were employed to improve detection, independent of breast density, in conjunction with mechatronic and automated approaches for accurate image acquisition and precise interventional workflow. First, a mechatronic guidance system for US-guided biopsy under high-resolution PEM localization was developed to improve spatial sampling of early-stage breast cancers. Validation and phantom studies showed accurate needle positioning and 3D spatial sampling under simulated PEM localization. Subsequently, a whole-breast spatially-tracked 3DUS system for point-of-care screening was developed, optimized, and validated within a clinically-relevant workspace and healthy volunteer studies. To improve robust image acquisition and adaptability to diverse patient populations, an alternative, cost-effective, portable, and patient-dedicated 3D automated breast (AB) US system for point-of-care screening was developed. Validation showed accurate geometric reconstruction, feasible clinical workflow, and proof-of-concept utility across healthy volunteers and acquisition conditions. Lastly, an orthogonal acquisition and 3D complementary breast (CB) US generation approach were described and experimentally validated to improve spatial resolution uniformity by recovering poor out-of-plane resolution. These systems developed and described throughout this dissertation show promise as alternative, cost-effective, robust, and high-resolution approaches for improving early detection and definitive diagnosis. Consequently, these contributions may advance breast cancer-related equities and improve outcomes in increased-risk populations and limited-resource settings

Mechanoresponsive drug delivery materials

Stimuli-responsive drug delivery materials release their payloads in response to physiological or external cues and are widely reported for stimuli such as pH, temperature, ionic strength, electrical potential, or applied magnetic field. While a handful of reports exist on materials responsive to mechanical stimuli, this area receives considerably less attention. This dissertation therefore explores three-dimensional networks and polymer-metal composites as mechanoresponsive biomaterials by using mechanical force to either trigger the release of entrapped agents or change the conformation of implants. At the nanoscale, shear is demonstrated as a mechanical stimulus for the release of a monoclonal antibody from nanofibrous, low molecular weight hydrogels formed from bio-inspired small molecule gelators. Using their self-healing, shear-thinning properties, mechanoresponsive neutralization of tumor necrosis factor alpha (TNFα) in a cell culture bioassay is achieved, suggesting utility for treating rheumatoid arthritis. Reaching the microscale, mechanical considerations are incorporated within the design of cisplatin-loaded meshes for sustained local drug delivery, which are fabricated through electrospinning a blend of polycaprolactone and poly(caprolactone-co-glycerol monostearate). These meshes are compliant, amenable to stapling/suturing, and they exhibit bulk superhydrophobicity (i.e., extraordinary resistance to wetting), which sustains release of cisplatin >90 days in vitro and significantly delays tumor recurrence in an in vivo murine lung cancer resection model. This polymer chemistry/processing strategy is then generalized by applying it to the poly(lactide-co-glycolide) family of biomedical polymers. As a macroscopic approach, a tunable, tension-responsive multilayered drug delivery device is developed, which consists of a water-absorbent core flanked by two superhydrophobic microparticle coatings. Applied strain initiates coating fracture to cause core hydration and subsequent drug release, with rates dependent on strain magnitude. Finally, macroscopic, shape-changing polymer-composite materials are developed to improve the current functionality of breast biopsy markers. This shape change provides a means to prevent marker migration from its intended site—a current clinical problem. In summary, mechanoresponsive systems are described, ranging from the nano- to macroscopic scale, for applications in drug delivery and biomedical devices. These studies add to the nascent field of mechanoresponsive biomedical materials and the arsenal of drug delivery techniques required to combat cancer and other medical ailments.2017-10-27T00:00:00

Anniversary Paper: Evolution of ultrasound physics and the role of medical physicists and the AAPM and its journal in that evolution

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134810/1/mp2048.pd