Biology subjects

Salahshoor, H.

Publications and source records attributed to Salahshoor, H..

6 recordsLinked to original sources

bioRxiv2023

Effects of focused ultrasound in a "clean" mouse model of ultrasonic neuromodulation

Recent studies on ultrasonic neuromodulation (UNM) in rodents have shown that focused ultrasound (FUS) can activate peripheral auditory pathways, leading to off-target and brain-wide excitation, which obscures the direct activation of the target area by FUS. To address this issue, we developed a new mouse model, the double transgenic Pou4f3+/DTR x Thy1-GCaMP6s, which allows for inducible deafening using diphtheria toxin and minimizes off-target effects of UNM while allowing effects on neural activity to be visualized with fluorescent calcium imaging. Using this model, we found that the auditory confounds caused by FUS can be significantly reduced or eliminated within a certain pressure range. At higher pressures, FUS can result in focal fluorescence dips at the target, elicit non-auditory sensory confounds, and damage tissue, leading to spreading depolarization. Under the acoustic conditions we tested, we did not observe direct calcium responses in the mouse cortex. Our findings provide a cleaner animal model for UNM and sonogenetics research, establish a parameter range within which off-target effects are confidently avoided, and reveal the non-auditory side effects of higher-pressure stimulation.

neuroscience↗

bioRxiv2022

A model-free Data-Driven paradigm for in situ patient-specific prediction of human brain response to ultrasound stimulation

We present a class of model-free Data-Driven solvers that effectively enable the utilization of in situ and in vivo imaging data directly in full-scale calculations of the mechanical response of the human brain to sonic and ultrasonic stimulation, entirely bypassing the need for analytical modeling or regression of the data. The well-posedness of the approach and its convergence with respect to data are proven analytically. We demonstrate the approach, including its ability to make detailed spatially-resolved patient-specific predictions of wave patterns, using public-domain MRI images, MRE data and commercially available solid-mechanics software.

biophysics↗

bioRxiv2022

Geometric effects in gas vesicle buckling under ultrasound

Acoustic reporter genes based on gas vesicles (GVs) have enabled the use of ultrasound to noninvasively visualize cellular function in vivo. The specific detection of GV signals relative to background acoustic scattering in tissues is facilitated by nonlinear ultrasound imaging techniques taking advantage of the sonomechanical buckling of GVs. However, the effect of geometry on the buckling behavior of GVs under exposure to ultrasound has not been studied. To understand such geometric effects, we developed computational models of GVs of various lengths and diameters and used finite element simulations to predict their threshold buckling pressures and post-buckling deformations. We demonstrated that the GV diameter has an inverse cubic relation to the threshold buckling pressure, whereas length has no substantial effect. To complement these simulations, we experimentally probed the effect of geometry on the mechanical properties of GVs and the corresponding nonlinear ultrasound signals. The results of these experiments corroborate our computational predictions. This study provides fundamental insights into how geometry affects the sonomechanical properties of GVs, which, in turn, can inform further engineering of these nanostructures for high-contrast, nonlinear ultrasound imaging. STATEMENT OF SIGNIFICANCEGas vesicles (GVs) are an emerging class of genetically encodable and engineerable imaging agents for ultrasound whose sonomechanical buckling generates nonlinear contrast to enable sensitive and specific imaging in highly scattering biological systems. Though the effect of protein composition on GV buckling has been studied, the effect of geometry has not previously been addressed. This study reveals that geometry, especially GV diameter, significantly alters the threshold acoustic pressures required to induce GV buckling. Our computational predictions and experimental results provide fundamental understanding of the relationship between GV geometry and buckling properties and underscore the utility of GVs for nonlinear ultrasound imaging. Additionally, our results provide suggestions to further engineer GVs to enable in vivo ultrasound imaging with greater sensitivity and higher contrast.

biophysics↗

bioRxiv2022

Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET

Gas vesicles (GVs) are gas-filled protein nanostructures employed by several species of bacteria and archaea as flotation devices to enable access to optimal light and nutrients. The unique physical properties of GVs have led to their use as genetically-encodable contrast agents for ultrasound and MRI. Currently, however, the structure and assembly mechanism of GVs remain unknown. Here we employ cryo-electron tomography to reveal how the GV shell is formed by a helical filament of highly conserved GvpA subunits. This filament changes polarity at the center of the GV cylinder--a site that may act as an elongation center. High-resolution subtomogram averaging reveals a corrugated pattern of the shell arising from polymerization of GvpA into a {beta}-sheet. The accessory protein GvpC forms a helical cage around the GvpA shell, providing structural reinforcement. Together, our results help explain the remarkable mechanical properties of GVs and their ability to adopt different diameters and shapes.

molecular biology↗

bioRxiv2021

Mechanics Of Ultrasonic Neuromodulation In A Mouse Subject

Ultrasound neuromodulation (UNM), where a region in the brain is targeted by focused ultrasound (FUS), which, in turn, causes excitation or inhibition of neural activity, has recently received considerable attention as a promising tool for neuroscience. Despite its great potential, several aspects of UNM are still unknown. An important question pertains to the off-target sensory effects of UNM and their dependence on stimulation frequency. To understand these effects, we have developed a finite-element model of a mouse, including elasticity and viscoelasticity, and used it to interrogate the response of mouse models to focused ultrasound (FUS). We find that, while some degree of focusing and magnification of the signal is achieved within the brain, the induced pressure-wave pattern is complex and delocalized. In addition, we find that the brain is largely insulated, or cloaked, from shear waves by the cranium and that the shear waves are largely carried away from the skull by the vertebral column, which acts as a waveguide. We find that, as expected, this waveguide mechanism is strongly frequency dependent, which may contribute to the frequency dependence of UNM effects. Our calculations further suggest that off-target skin locations experience displacements and stresses at levels that, while greatly attenuated from the source, could nevertheless induce sensory responses in the subject.

neuroscience↗

bioRxiv2020

Transcranial Focused Ultrasound Generates Skull-Conducted Shear Waves: Computational Model and Implications for Neuromodulation

Focused ultrasound (FUS) is an established technique for non-invasive surgery and has recently attracted considerable attention as a potential method for non-invasive neuromodulation. While the pressure waves generated by FUS in this context have been extensively studied, the accompanying shear waves are often neglected due to the relatively high shear compliance of soft tissues. However, in bony structures such as the skull, acoustic pressure can also induce significant shear waves that could propagate outside the ultrasound focus. Here, we investigate wave propagation in the human cranium by means of a finite-element model that accounts for the anatomy, elasticity and viscoelasticity of the skull and brain. We show that, when a region on the frontal lobe is subjected to FUS, the skull acts as a wave guide for shear waves, resulting in their propagation to off-target structures such as the cochlea. This effect helps explain the off-target auditory responses observed during neuromodulation experiments and informs the development of mitigation and sham control strategies.

biophysics↗