Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.
Transcranial magnetic resonance-guided focused ultrasound continues to gain traction as a noninvasive treatment option for a variety of pathologies. Focusing ultrasound through the skull can be accomplished by adding a phase correction to each element of a hemispherical transducer array. The phase corrections are determined with acoustic simulations that rely on speed of sound estimates derived from CT scans. While several studies have investigated the relationship between acoustic velocity and CT Hounsfield units (HUs), these studies have largely ignored the impact of X-ray energy, reconstruction method, and reconstruction kernel on the measured HU, and therefore the estimated velocity, and none have measured the relationship directly. In this paper, 91 ex vivo human skull fragments from two skulls are imaged by 80 CT scans with a variety of energies and reconstruction methods. The average HU from each fragment is found for each scan and correlated with the speed of sound measured using a through transmission technique in that fragment. As measured by the -squared value, the results show that CT is able to account for 23%-53% of the variation in velocity in the human skull. Both the X-ray energy and the reconstruction technique significantly alter the -squared value and the linear relationship between HU and speed of sound in bone. Accounting for these variations will lead to more accurate phase corrections and more efficient transmission of acoustic energy through the skull.
Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.
The InSightec Exablate system is the standard of care used for transcranial focused ultrasound ablation treatments in the United States. The system calculates phase corrections that account for aberrations caused by the human skull. This work investigates whether skull aberration correction can be improved by comparing the standard of care InSightec ray tracing method with the hybrid angular spectrum (HAS) method and the gold standard hydrophone method. Three degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). Phase corrections were calculated using four different methods (straight ray tracing, InSightec ray tracing, HAS, and hydrophone) and were used to drive the transducer. 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. For three skulls, the InSightec ray tracing method achieved 52 ± 21% normalized target intensity (normalized to hydrophone), 76 ± 17% normalized peak intensity, and 0.72 ± 0.47 mm positioning error. The HAS method achieved 74 ± 9% normalized target intensity, 81 ± 9% normalized peak intensity, and 0.35 ± 0.09 mm positioning error. The InSightec-to-HAS improvement in focal spot targeting provides promise in improving treatment outcomes. These improvements to skull aberration correction are also highly relevant for the applications of focused ultrasound neuromodulation and blood brain barrier opening, which are currently being translated for human use.
The collapse of substantial numbers of large multinational banking corporations in recent years has prompted regulatory authorities to raise both disclosure and transparency requirements on banks. Banking customers have also called for additional protection against unconscionable 57 practices, and for greater transparency and product information. The literature reveals that transparency positively influences customer behaviour. However, the mediating effect of service charge transparency on the relationship between corporate social responsibility and customer behaviour is a neglected topic. The findings in this research revealed that corporate social responsibility has a positive and significant influence on service charge transparency, customer repurchase intention and word-of-mouth intention. The results also confirmed that service charge transparency has a positive and significant influence on customer repurchase intention and word-of-mouth. Furthermore, they revealed that service charge transparency plays a mediating role in the respective relationships between corporate social responsibility and the two dimensions of consumer behaviour, customer repurchase intention and word-of-mouth intention.
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