Ultrasonic medicine

Mechanics in ultrasonic medicine


Ultrasound is a widely used medical imaging and therapeutic modality that enables deep and non-invasive observation and perturbation of internal anatomy and physiology. Mechanics plays an important role in all practices of ultrasonic medicine, including (i) diagnostic techniques (e.g., acoustic imaging such as elastography), and (ii) therapeutic procedures (e.g. ultrasonic therapy such as neuromodulation). A common challenge in all these types of medical procedures pertains to developing computational models that can accurately predict the outcomes of interventions. Our lab aims for high-fidelity in-silico models to understand and predict the behavior of biological systems subject to ultrasonic waves across scales. Below are two projects that showcase our lab's efforts on this research thrust:

Mechanics of Gas Vesicles as Acoustoelastic Biomolecule

Gas Vesicles (GVs) are a unique class of genetically encoded protein nanocompartments that are typically 200-800 nm in size, assembled as air-filled hollow nanostructures enclosed by a ~2 nm-thick protein shell which only allows for permeation of gas molecules from the surrounding environment. GVs are an emerging class of genetically encodable contrast agents for ultrasonic applications whose mechanical response enables sensitive and specific imaging in highly scattering biological systems. A thorough understanding of mechanics of GVs is key to a wide spectrum of their application in both imaging and therapeutic modalities. With recourse to computational modeling, we aim to shed light on their mechanical response subject to ultrasound. For example, in order to exploit this buckling mechanism for US imaging, we have developed an experimentally-verified predictive computational model of GVs subjected to US pressure, and have quantified the effect of geometric features on the GV buckling.

Sonomechanical buckling of GVs
Left: Diameter and length sensitivity of Gas Vesicle (GV) buckling under ultrasound. We demonstrated that the GV diameter has an inverse cubic relation to the threshold buckling pressure, whereas length has no substantial effect. Right: Experimental validation of the GV geometry-buckling relationship with recourse to cryo-EM and nonlinear ultrasound imaging.

We have further investigated a protein-made helical cage around the GV shell, that is naturally found in wild-type GVs, and the effect thereof on their mechanical buckling. Our in-silico findings are corroborated with experimental observations. These computational models provide fundamental understanding of GV mechanics and enable pathways to further engineer GVs to enhance in vivo ultrasound biomolecular imaging with greater sensitivity and higher contrast.

Ultrasonic Neuromodulation

Ultrasound neuromodulation (UNM) has recently received significant attention as a promising tool for neuroscience, where a region in the brain is targeted by focused ultrasound (FUS), which, in turn, causes excitation or inhibition of neural activity. Despite its great potential in neuroscience, several aspects of UNM are still unknown. An important question pertains to the off-target effects of UNM and their dependency on stimulation parameters. For example, experiments have shown that while the visual cortex is targeted by FUS, the subject elicits auditory responses.


Computational ultrasonic neuromodulation in the human head
Computational mechanics of ultrasonic neuromodulation in human head.

To understand these effects, we have developed state of the art finite element models of a human head and a mouse for modeling ultrasound (US) neuromodulation, where we account for the intricate geometry and the viscoelastic mechanical behaviors of individual tissues. We demonstrate that, upon subjecting a region on the scalp above the skull to focused ultrasound (FUS) pressure, the bone acts as a waveguide for ultrasound-induced shear waves, carrying them away from the FUS target. As we demonstrate in our human study, this phenomenon help explain the off-target auditory responses observed during neuromodulation experiments. We further investigate the off-target UNM effects in a mouse subject by characterizing the resultant displacements, pressure and shear stresses at different locations on the mouse skin as a function of FUS frequency. Tissue motion at these locations can potentially cause sensory effects. Our results could help explain the off-target responses observed during UNM experiments and inform the development of mitigation and sham control strategies.