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Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique capable of manipulating both cortical and subcortical ...

University of Calgary

We present a new formulation for a breast tissue-mimicking phantom for combined microwave and ultrasound imaging to assist breast cancer detection. Formulations based on coconut oil, canola oil, agar and glass beads were used to mimic skin and fat tissues. First, 36 recipes were fabricated, and properties were measured to determine the relationship and possible interaction between ingredients with the ultrasound and microwave properties. Based on these results, the formulae were developed to mimic different tissues found in breast, including skin, fat, fibroglandular, and tumour tissues. All phantoms contained a base of agar and glass beads at different proportions depending on the tissue mimicked. Tumour and fibroglandular tissues were best mimicked by adding polyvinylpyrrolidone (PVP), while using coconut oil for skin and canola oil for fat produced the best results. Five final phantoms with different internal structures were fabricated and imaged using B-mode ultrasound and a microwave transmission system. Microwave permittivity maps were obtained from the microwave system and compared to ultrasound images. The structure and composition of the phantoms were all confirmed through this microwave and ultrasound imaging.

Breast tissue mimicking phantoms for combined ultrasound and microwave imaging.

. Focused ultrasound (FUS) neuromodulation non-invasively alters brain activity, likely via acoustic radiation force with dynamics of the pulse repetition frequency (PRF). PRF impacts neuromodulation as well as indirect auditory activation, a confound linked to skull vibrations. This study aimed to minimize these vibrations, by adjusting and randomizing PRF, and determine their impact on FUS-induced motor activity. We hypothesized that: the skull would vibrate most at a specific PRF; randomizing PRF would reduce skull vibrations without affecting motor responses; and FUS would yield motor activity while actuator-induced skull vibrations would not.. Three objectives were studied in parallel using C57Bl/6 mice (= number of mice used per objective). First, skull vibration amplitude, measured as a percentage of maximum amplitude per treatment, was recorded via contact microphone over a range of PRFs to assess the PRF-dependency of skull vibrations (= 19). Vibrations were then compared between random and fixed PRFs (= 15). Lastly, motor responses were compared between fixed 1.5 kHz PRF FUS, random PRF FUS, air-puff stimulation, sham stimulation, and vibration induction via piezoelectric actuator (= 30).The study found amplitude peaked at 1.51 kHz (88.1 ± 11.5%), significantly higher than at 0.54 kHz (75.5 ± 15.1%;= 0.0149). Random PRF reduced amplitude by 4.2% (= 0.0181). Motor response rates to actuator-induced skull vibrations at the PRF (5.73 ± 6.96%) and its third harmonic (22.9 ± 22.7%) were not significantly different than sham (14.1 ± 11.6%), but lower than FUS (70.2 ± 16.3%;< 0.0001).. Based on these results, PRF near 0.5 kHz may best avoid skull vibrations, while random PRF could be utilized to slightly reduce vibration amplitude. The results also suggested that skull vibrations likely do not significantly impact motor responses to FUS neuromodulation.

Investigating the impact of skull vibrations on motor responses to focused ultrasound neuromodulation in small rodents and methods to mitigate them.

Biaxial driving is a new driving technique that allows the steering of the ultrasound field generated by a single-element piezoceramic transducer. Because of their natural axisymmetric geometry, ultrasound generation with ring transducers can take advantage of the biaxial driving to change the focus of the beam generated by this type of transducer using only two driving signals. In this study, we applied the biaxial driving technique into a single-element PZT ring transducer operating at 500 kHz to produce a change in size and position of the focal spot while using the 1st (482 kHz), 3rd (1.362 MHz) and 5th (2.62 MHz) harmonic excitation. The transducer had a thickness of 2.85 mm, an inner diameter of 9.75 mm and a ring width of 2.0 mm, and two pairs of electrodes as required for biaxial driving. Simulation and experimental results showed that both the focal area and the distance at which the focal area centre was located changed as a function of the phase and power difference between the two driving signals. Experimental results showed that the focal area could be reduced from 31.6 mm (conventional driving) to 3.4 mm (89 % reduction) when using the first harmonic excitation. For the third harmonic, the focal area could be reduced from 4.0 mm (conventional driving) to 3.3 mm (17.5 % reduction). For the fifth harmonic, the focal area could be reduced from 1.7 mm (conventional driving) to 1 mm (41.7 % reduction). Results also demonstrated the centre of the focus could be displaced between 3.0 mm and 9.3 mm from the surface of the transducer when using the first harmonic, between 7.3 mm and 8.4 mm at the third harmonic, and between 4.9 mm and 8.2 mm at the fifth harmonic. The reduction in the focus area, as well as the possibility to displace the focus dynamically will be advantageous for preclinical applications of focused ultrasound, especially on drug delivery and neuromodulation studies in small rodents.

Higher harmonics dynamic focalization in single-element ring transducers using biaxial driving.

Biaxial driving can more efficiently convert electrical power to forward acoustic power in piezoelectric materials, and the interaction between the orthogonal electric fields can produce a combination of extensional and shear deformations as a function of the phase difference between them to allow dynamic steering of the beam with a single-element. In this study, we demonstrate for the first time the application of a single-element biaxially driven ring transducerfor blood-brain barrier opening in mice, and compare it to that achieved with a conventional single-element highly focused (F# = 0.7) spherical transducer operating at a similar frequency. Transcranial focused ultrasound (0.45 MPa, 10 ms pulse length, 1 Hz repetition frequency, 30 s duration) was applied bilaterally to mice with a 40l/kg bolus of Definitymicrobubbles, employing either a single-element biaxial ring (1.482 MHz, 10 mm inner diameter, 13.75 mm outer diameter) or spherical (1.5 MHz, 35 mm diameter, F# = 0.7; RK50, FUS Instruments) transducer on each side. Follow-up MRI scans (T1 pre- and post- 0.2 mmol/kg Gd injection, T2) were acquired to assess blood-brain barrier opening volume and potential damage. Compared to blood-brain barrier opening achieved with a conventional single-element spherical focused transducer, the opening volume achieved with a single-element biaxial ring transducer was 35% smaller (= 0.002) with a device of a ring diameter of 40% the aperture size. Axial refocusing was further demonstrated with the single-element biaxial ring transducer, yielding a 1.63 mm deeper, five-fold larger opening volume (= 0.048) relative to its small-focus mode. The biaxial ring transducer achieved a more localized opening compared to the spherical focused transducer under the same parameters, and further enabled dynamic axial refocusing with a single-element transducer with a smaller fabrication footprint.

Siyun Li

Department of Radiology,
Cumming School of Medicine,
Department of Radiology, Cumming School of Medicine

University of Calgary

Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

Siyun Li

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Radiology,Cumming School of Medicine,Department of Radiology, Cumming School of Medicine

University of Calgary

Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

Department of Radiology,
Cumming School of Medicine,
Department of Radiology, Cumming School of Medicine