Bradley E. Treeby's research while affiliated with University College London and other places

Objective. Focused ultrasound spinal cord neuromodulation has been demonstrated in small animals. However, most of the tested neuromodulatory exposures are similar in intensity and exposure duration to the reported small animal threshold for possible spinal cord damage. All efforts must be made to minimize the risk and assure the safety of potential human studies, while maximizing potential treatment efficacy. This requires an understanding of ultrasound propagation and heat deposition within the human spine. Approach. Combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level via two approaches (a) the posterior acoustic window between vertebral posterior arches, and (b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of fifty 0.1 s pulses (pulse repetition frequency: 0.33 Hz, free-field spatial peak pulse-averaged intensity: 10 W cm⁻²) were simulated for four subjects and for ±10 mm translational and ±10∘ rotational source positioning errors. Main results. Target pressures ranged between 20%–70% of free-field spatial peak pressures with the posterior approach, and 20%–100% with the lateral approach. When the posterior source was optimally positioned, peak spine heating values were below 1 ∘C, but source mispositioning resulted in bone heating up to 4 ∘C. Heating with the lateral approach did not exceed 2 ∘C within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately two-fold between subjects. This results in a nearly ten-fold range between subjects in the target pressure achieved per degree of maximum heating. Significance. This study highlights the utility of trans-spine ultrasound simulation software and need for precise source-anatomy positioning to assure the subject-specific safety and efficacy of focused ultrasound spinal cord therapies.

Transcranial ultrasound stimulation (TUS) has emerged as a promising technique for non-invasive neuromodulation, but current systems lack the precision to target deep brain structures effectively. Here, we introduce an advanced TUS system that achieves unprecedented precision in deep brain neuromodulation. The system features a 256-element, helmet-shaped transducer array operating at 555 kHz, coupled with a stereotactic positioning system, individualised treatment planning, and real-time monitoring using functional MRI. In a series of experiments, we demonstrate the system's ability to selectively modulate the activity of the lateral geniculate nucleus (LGN) and its functionally connected regions in the visual cortex. Participants exhibited significantly increased visual cortex activity during concurrent TUS and visual stimulation, with high reproducibility across individuals. Moreover, a theta-burst TUS protocol induced robust neuromodulatory effects, with decreased visual cortex activity observed for at least 40 minutes post-stimulation. These neuromodulatory effects were specific to the targeted LGN, as confirmed by control experiments. Our findings highlight the potential of this advanced TUS system to non-invasively modulate deep brain circuits with high precision and specificity, offering new avenues for studying brain function and developing targeted therapies for neurological and psychiatric disorders. The unprecedented spatial resolution and prolonged neuromodulatory effects demonstrate the transformative potential of this technology for both research and clinical applications, paving the way for a new era of non-invasive deep brain neuromodulation.

Existing data on the acoustic properties of low-temperature biological materials is limited and widely dispersed across fields. This makes it difficult to employ this information in the development of ultrasound applications in the medical field, such as cryosurgery and rewarming of cryopreserved tissues. In this review, the low-temperature acoustic properties of biological materials, and the measurement methods used to acquire them were collected from a range of scientific fields. The measurements were reviewed from the acoustic set-up to thermal methodologies for samples preparation, temperature monitoring, and system insulation. The collected data contain the longitudinal and shear velocity, and attenuation coefficient of biological soft tissues and biologically relevant substances - water, aqueous solutions, and lipids - in the temperature range down to -50°C and in the frequency range from 108 kHz to 25 MHz. The Multiple-Reflection Method (MRM) was found to be the preferred method for low-temperature samples, with a buffer-rod inserted between the transducer and sample to avoid direct contact. Longitudinal velocity changes are observed through the phase transition zone, which is sharp in pure water, and occurs more slowly and at lower temperatures with added solutes. Lipids show longer transition zones with smaller sound velocity changes; with the longitudinal velocity changes observed during phase transition in tissues lying between these two extremes. More general conclusions on the shear velocity and attenuation coefficient at low-temperatures are restricted by the limited data. This review enhance knowledge guiding for further development of ultrasound applications in low-temperature biomedical fields, and may help to increase the precision and standardisation of low-temperature acoustic property measurements.

Focused ultrasound spinal cord neuromodulation studies have demonstrated the capacity for neuromodulation of the spinal cord in small animals. The safe and efficacious translation of these approaches to human scale requires an understanding of ultrasound propagation and heat deposition within the human spine. To address this, combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level of the cervical spine via two approaches a) the posterior acoustic window between vertebral posterior arches, or b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of 150 0.1 s pulses with a pulse repetition frequency of 0.33 Hz and free-field spatial peak pulse-averaged intensity of 10 W/cm^2 were simulated for the CT volumes of four subjects and for ±10 mm translational and ±10 degrees rotational source positioning errors. Target pressures ranged between 20% and 70% of free-field spatial peak pressures with the posterior approach, and 20% and 100% with the lateral approach. When the source was optimally positioned with the posterior approach, peak spine heating values were below 1 degC, but source mis-positioning resulted in bone heating up to 4 degC. Heating with the lateral approach did not exceed 2 degC within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately twofold between subjects. This results in a nearly tenfold range in the target pressure achieved per degree of maximum heating between subjects. This study highlights the importance of developing trans-spine ultrasound simulation software for the assurance of subject-specific safety and efficacy of focused ultrasound spinal cord therapies.

As transcranial ultrasound stimulation (TUS) advances as a precise, non-invasive neuromodulatory method, there is a need for consistent reporting standards to enable comparison and reproducibility across studies. To this end, the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) formed a subcommittee of experts across several domains to review and suggest standardised reporting parameters for low intensity TUS, resulting in the guide presented here. The scope of the guide is limited to reporting the ultrasound aspects of a study. The guide and supplementary material provide a simple checklist covering the reporting of: (1) the transducer and drive system, (2) the drive system settings, (3) the free field acoustic parameters, (4) the pulse timing parameters, (5) in situ estimates of exposure parameters in the brain, and (6) intensity parameters. Detailed explanations for each of the parameters, including discussions on assumptions, measurements, and calculations, are also provided.

Measuring acoustic properties in extreme environments, involving hazardous chemical samples or temperature above 50ºC or below 0ºC, is challenging yet crucial for understanding waveform interactions with materials, with applications in fields like non-destructive testing (NDT) and medical applications. Multiple-reflection methods (MRM), using a buffer-rod between transducer and sample, offer a solution. Yet, the impact of variables like contact force, buffer-rod size, and surface roughness on the accuracy and precision of MRM measurements remains unvalidated. To address this, we introduce a system and experiments to quantify the accuracy of measurements of acoustic attenuation coefficient. Results demonstrate the substantial impact of contact force on system accuracy and precision, reflected by a decrease in the measured attenuation coefficient at 0.5 MHz from 3.8 to 1.5dB/cm with increasing contact force. Effects of buffer-rod width were less pronounced and supported the theory that a cylindrical buffer-rod with twice the radius of the transducer is sufficient. Interestingly, surface roughness, despite being over 150 times smaller than the wavelength of the acoustic signal, influences measurement accuracy. This study illuminates the crucial role of system factors on measurement accuracy and uncertainty, which will aid optimization of measurements for diverse practical applications.

Cryopreservation of large volumes of cells and tissues, followed by successful rewarming, promises to revolutionize organ transplantation by extending organ preservation times. This technology addresses a critical issue: over 6,000 individuals in the UK are awaiting organ transplants, yet an alarming 60% of donated organs go unused due to current preservation time limitations. A significant challenge lies in providing a rapid and uniform rewarming method for cryopreserved tissues. Ultrasound, capable of converting sound power into heat as it propagates through tissue, offers a promising solution. Nonetheless, before tapping into ultrasound’s potential for rewarming experiments, a fundamental understanding of the acoustic properties of tissues, which vary with temperature and during phase change, is essential. This study employs the multiple-reflection method (MRM), with buffer-rod positioned between the transducer and sample, to measure the acoustic attenuation coefficient and sound speed in biological relevant materials and the primary components of tissues, such as water and lipids, across a temperature range of 20 to −100ºC. Concurrently, the acoustic properties of commonly used cryopreservation solutions were assessed. These data will facilitate computational simulation of acoustic power delivery and the resulting temperature distributions, enabling planning and monitoring of tissue rewarming, which is critical to its success.