Kinematics of the Upper Eyelid and the Globe During Downward Excursion With Comparative Analysis in Patients With Thyroid Eye Disease.

PURPOSE: To analyze the kinematics of the upper eyelid and the globe on downward excursion for potential use in monitoring thyroid eye disease (TED) progression in an objective manner. METHODS: Ten normal volunteers and 10 patients with TED were studied. A high-speed (240 fps) digital camera with a coaxial light source set at a constant distance from the subjects' eyes was used to record the excursion of the upper eyelid and the globe from extreme upgaze to extreme downgaze. Clinical data, including age, gender, race, thyroid function tests, Vision, Inflammation/Congestion, Strabismus/motility restriction, Appearance/exposure score (primary surgeons' preference of TED grading system), exophthalmometry, and eyelid measurements were collected for all patients with TED. Frame-by-frame analyses of the videos were performed using Python software (version 3.6) and the Open Source Computer Vision Library. Temporal resolution was obtained by measuring the number of frames from initiation of eyelid and globe movement from extreme upgaze (t 0 ) to extreme downgaze (t f ). Spatial resolution was obtained by measuring the number of pixels the eyelid margin and the globe traversed from t 0 to t f . The data were then plotted on a graph to calculate the velocity of the upper eyelid and the globe during downward excursion. RESULTS: Velocimetric calculations using high-speed photography suggests that downward excursion of the upper eyelid, and the globe occurs in 2 phases: the acceleration phase and the deceleration phase. Comparative analysis of slow-motion videography demonstrates that patients with TED were found to have attenuation in the early acceleration phase of upper eyelid excursion compared with normal subjects. In patients with TED, the difference in velocity between the eyelid and the globe occurs in the early deceleration phase. CONCLUSIONS: The upper eyelid normally synchronizes intimately with the globe during downward eye movement. Data from this study reveal that attenuation mostly in the early deceleration phase of eyelid movement relative to the globe accounts for the dynamic eyelid lag seen on clinical examination. Further analysis is needed to show if a quantified von Graefe sign can be used as an objective means of monitoring progression in TED.

High-resolution acoustic mapping of tunable gelatin-based phantoms for ultrasound tissue characterization.

Background: The choice of gelatin as the phantom material is underpinned by several key advantages it offers over other materials in the context of ultrasonic applications. Gelatin exhibits spatial and temporal uniformity, which is essential in creating reliable tissue-mimicking phantoms. Its stability ensures that the phantom's properties remain consistent over time, while its flexibility allows for customization to match the acoustic characteristics of specific tissues, in addition to its low levels of ultrasound scattering. These attributes collectively make gelatin a preferred choice for fabricating phantoms in ultrasound-related research. Methods: We developed gelatin-based phantoms with adjustable parameters and conducted high-resolution measurements of ultrasound wave attenuation when interacting with the gelatin phantoms. We utilized a motorized acoustic system designed for 3D acoustic mapping. Mechanical evaluation of phantom elasticity was performed using unconfined compression tests. We particularly examined how varying gelatin concentration influenced ultrasound maximal intensity and subsequent acoustic attenuation across the acoustic profile. To validate our findings, we conducted computational simulations to compare our data with predicted acoustic outcomes. Results: Our results demonstrated high-resolution mapping of ultrasound waves in both gelatin-based phantoms and plain fluid environments. Following an increase in the gelatin concentration, the maximum intensity dropped by 30% and 48% with the 5 MHz and 1 MHz frequencies respectively, while the attenuation coefficient increased, with 67% more attenuation at the 1 MHz frequency recorded at the highest concentration. The size of the focal areas increased systematically as a function of increasing applied voltage and duty cycle yet decreased as a function of increased ultrasonic frequency. Simulation results verified the experimental results with less than 10% deviation. Conclusion: We developed gelatin-based ultrasound phantoms as a reliable and reproducible tool for examining the acoustic and mechanical attenuations taking place as a function of increased tissue elasticity and stiffness. Our experimental measurements and simulations gave insight into the potential use of such phantoms for mimicking soft tissue properties.

Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids.

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality that uses precise acoustic energy to ablate cancerous tissues through coagulative necrosis. In this context, we investigate the efficacy of HIFU ablation in two distinct cellular configurations, namely 2D monolayers and 3D spheroids of epithelial breast cancer cell lines (MDA-MB 231 and MCF7). The primary objective is to compare the response of these two in vitro models to HIFU while measuring their ablation percentages and temperature elevation levels. HIFU was systematically applied to the cell cultures, varying ultrasound intensity and duty cycle during different sonication sessions. The results indicate that the degree of ablation is highly influenced by the duty cycle, with higher duty cycles resulting in greater ablation percentages, while sonication duration has a minimal impact. Numerical simulations validate experimental observations, highlighting a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated duty cycles. This study contributes to a comprehensive understanding of acoustic energy conversion within the biological system during HIFU treatment for 2D versus 3D ablation targets, holding potential implications for refining and personalizing breast cancer therapeutic strategies.

Modeling of Calcium-dependent Low Intensity Low Frequency Ultrasound Modulation of a Hodgkin-Huxley Neuron.

Non-invasive low intensity, low frequency ultrasound is a progressive neuromodulation approach that can reach deep brain areas with peak spatial and temporal resolution for highly-targeted diagnostic and therapeutic purposes. Coupling the ultrasound mechanical effects to the neural membrane comprises different mechanisms that are, to-date, still a topic of debate. The availability of calcium ions in the extracellular medium is of high significance when it comes to the effect of ultrasound on the neural tissue. Whereby the generated calcium influx can directly affect the voltage-gated ion channels, amplifying their action. We modeled the flexoelectric-induced effects of ultrasound to a single firing neuron, taking into consideration the effect of calcium channel embedding into the neural membrane on the neuron's firing rate, latency response, peak-to-peak voltage, and general shape of the action potential.Clinical Relevance- Upon Ultrasound sonication, the mechanical waves interact with the neural membrane and alter the kinetics of the calcium channels, thus changing the neural response.

Modeling ultrasound modulation of neural function in a single cell.

Background: Low intensity ultrasound stimulation has been shown to non-invasively modulate neural function in the central nervous system (CNS) and peripheral nervous system (PNS) with high precision. Ultrasound sonication is capable of either excitation or inhibition, depending on the ultrasound parameters used. On the other hand, the mode of interaction of ultrasonic waves with the neural tissue for effective neuromodulation remains ambiguous. New method: Here within we propose a numerical model that incorporates the mechanical effects of ultrasound stimulation on the Hodgkin-Huxley (HH) neuron by incorporating the relation between increased external pressure and the membrane induced tension, with a stress on the flexoelectric effect on the neural membrane. The external pressure causes an increase in the total tension of the membrane thus affecting the probability of the ion channels being open after the conformational changes that those channels undergo. Results: The interplay between varying the acoustic intensities and frequencies depicts different action potential suppression rates, whereby a combination of low intensity and low frequency ultrasound sonication proved to be the most effective in modulating neural function.Comparison with Existing Methods: Our method solely depends on the HH model of a single neuron and the linear flexoelectric effect of the dielectric neural membrane, when under an ultrasound-induced mechanical strain, while varying the ion-channels conductances based on different sonication frequencies and intensities. We study the effect of ultrasound parameters on the firing rate, latency, and action potential amplitude of a HH neuron for a better understanding of the neuromodulation modality of ultrasound stimulation (in the continuous and pulsed modes). Conclusions: This simulation work confirms the published experimental data that low intensity and low frequency ultrasound sonication has a higher success rate of modulating neural firing.