Experimental analysis and validation of ultrasonic torsional waves

Resumen

The structural microarchitecture of soft tissue is getting attention among the biomechanical engineering community and rising interest in clinical diagnosis in a broad spectrum of specialities. The new scientific concept of torsional waves (TW) ultrasound will enable the in vivo and noninvasive quantification of a new class of biomarkers. These biomarkers, direct measures of tissue mechanical properties, are intimately related to the structural microarchitecture of soft tissue and ideal for diagnostic applications. This concept will be validated by the novel technology proposed herein by generating and sensing torsional waves in soft tissue. The breakthrough that this new generation of physical-mechanical biomarkers implies will have a long-term impact. The elastic functionality of tissues is intimately linked to a variety of pathologies. Its quantitative measurement in vivo constitutes a disruptively new diagnostic principle proposed only recently. Well beyond birth and labour disorders (prematurity, induction failures, placenta, etc.), it has enormous potential of being extended to diagnose a growing range of highly prevalent pathologies, including solid tumours (e.g. prostate, cervix, breast, melanoma), connective tissue disorders (ligament injuries, ageing disorders), and liver fibrosis, to name a few. Quantifying the elastic functionality of the cervix is currently not a standard diagnostic tool since no elasticity quantifying technologies exist now or are still under early research. One of the most important potential torsional wave device applications will reduce infant mortality and childhood morbidity. By quantifying biomechanical properties of the cervix in at-risk women, sufficiently early detection of preterm birth may be identified so that suitable interventions can be implemented to delay delivery. The noninvasive in vivo quantification of the biomechanical properties of the cervix will be the clinical focus of this project. This will be accomplished by combining the underlying theory, the technological advances necessary for a proof-of-concept torsional wave diagnostic probe and model-based inverse algorithms to reconstruct the cervical stroma microarchitecture to predict its elastic evolution predict its structural ability to dilate. Finally, and most importantly, this project broadens the scope of applications, paving the way to any situation related to modifications of the collagen mechanics, like mechanobiological cell signalling, controlling tumour growth, inflammatory and healing processes, etc., and opening a new and broad field of research with impacting applications. The research group to which I belong has developed the torsion wave elastography technique and has patented an isotropic sensor validated in vivo by measuring under different conditions (pressure and angle of incidence) in pregnant women non-pregnant volunteers. At the same time, the validation was done against a rheometer with ex vivo tissue samples. My contribution to the work focuses on exploring new designs and validating the sensor against the gold standard: shear wave elastography using a Verasonics US research system(Vantage 256, Verasonics Inc., Redmond, WA, USA) and using mechanical testing. The validation was concentrated at the beginning employing tissue-mimicking phantoms, animal tissue, liver, and breast. Only when I entirely programmed the scripts for shear wave elasticity imaging and integrated the post process algorithms, I focused on scans of ex vivo samples of the human uterine cervix. This is due to the difficulty of obtaining these samples. This dissertation includes four main objectives (1) Quantification of tissue viscoelasticity using isotropic TWE probe; First validation against SWEI was done for ex vivo animal liver and tissue-mimicking hydrogel phantoms and only after, for ex vivo human uterine cervical tissue. Four rheological fitting models were used. As far as we know, these results are the first that are presented using this technique. (2) An additional step is to explore how the TW sensor behaves when measuring tissues with different layers, epithelial and connective. Being the first layer much thinner than the second. Therefore, and to check the type of waves propagating in shell-like elements, a new sensor was designed to measure corneas and have a concave shape. So, I explored tissue viscoelasticity in bounded media; Cornea designing and fabricating a modified isotropic TWE probe. (3) Assessment of shear stiffness of anisotropic soft tissue employing a new design of the TWE probe sectorized with three channels, capable of measuring in a single batch in three different directions. (4) Attempts to the nonlinear viscoelastic characterization of the cervical tissue. We proposed a nonlinear model and compared it with the models present in the literature.