Enhanced Detection of Bubble Emissions Through the Intact Spine for Monitoring Ultrasound-Mediated Blood-Spinal Cord Barrier Opening

Fletcher, Stecia-Marie P.; Ogrodnik, Natalia; O’Reilly, Meaghan A.

doi:10.1109/tbme.2019.2936972

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…Using ramped pressure exposures, during treatments, a change in the pressure based on a detected subharmonic was never achieved. The method of Fourier analysis used in real-time was described in 26 . There was one exception, at location 2 in pig 7, where a pressure drop was triggered at 46 s due to a false positive arising from a signal disruption during baseline measurements.…”

Section: Resultsmentioning

confidence: 99%

“…Acquired waveforms were digitized using a two-channel 14-bit PCI scope card (ATS460, Alazar Technologies Inc., QC, Canada). For pigs 5-8, the frequency content of acoustic emissions, analyzed as described in 26 , were plotted in real time and a detectable change in the subharmonic was used to trigger a 50% pressure drop, as described in 8 . If a pressure change was triggered, the pressure was maintained at 50% of the trigger level for the duration of the treatment.…”

Section: Methodsmentioning

confidence: 99%

“…However, in the past decade, preliminary research in animal models has indicated that the BSCB can be modified using FUS + MBs, similarly to the BBB 22 - 27 . To date, these studies have been limited to transvertebral studies in rodents 22 - 26 , in which the thickness and density of vertebral bone is not comparable with humans, or in rabbits, which have included pre-treatment laminectomies 27 . Although a laminectomy may be appropriate in cases of injury or focal tumors, there is a need to develop non-invasive approaches through the intact bone for this treatment to be relevant to diffuse disease, such as leptomeningeal metastases 28 or neurodegenerative diseases, like multiple sclerosis 29 or amyotrophic lateral sclerosis 30 , where treatment along large portions of the neuroaxis is required.…”

Section: Introductionmentioning

confidence: 99%

“…To address this, a dual aperture, cross-beam approach through the vertebral laminae using short burst, phase keying (SBPK) exposures has been proposed 35 . SBPK FUS exposures can be modified to leverage pulse inversion (PI) 36 to enhance detection of MB emissions through the intact spine 26 . SBPK FUS exposures have been shown to successfully open the BSCB in small animals, by our group 26 .…”

Section: Introductionmentioning

confidence: 99%

“…SBPK FUS exposures can be modified to leverage pulse inversion (PI) 36 to enhance detection of MB emissions through the intact spine 26 . SBPK FUS exposures have been shown to successfully open the BSCB in small animals, by our group 26 .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening

Fletcher¹,

Choi²,

Ogrodnik³

et al. 2020

Theranostics

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Blood-spinal cord barrier opening, using focused ultrasound and microbubbles, has the potential to improve drug delivery for the treatment of spinal cord pathologies. Delivering and detecting ultrasound through the spine is a challenge for clinical translation. We have previously developed short burst, phase keying exposures, which can be used in a dual-aperture configuration to address clinical scale targeting challenges. Here we demonstrate the use of these pulses for blood-spinal cord barrier opening, in vivo in pigs. Methods: The spinal cords of Yorkshire pigs (n=8) were targeted through the vertebral laminae, in the lower thoracic to upper lumbar region using focused ultrasound (486 kHz) and microbubbles. Four animals were treated with a combination of pulsed sinusoidal exposures (1.0-4.0 MPa, non-derated) and pulsed short burst, phase keying exposures (1.0-2.0 MPa, non-derated). Four animals were treated using ramped short burst, phase keying exposures (1.8-2.1 MPa, non-derated). A 250 kHz narrowband receiver was used to detect acoustic emissions from microbubbles. Blood-spinal cord barrier opening was assessed by the extravasation of Evans blue dye. Histological analysis of the spinal cords was used to assess tissue damage and excised vertebral samples were used in benchtop experiments. Results: Ramped short burst, phase keying exposures successfully modified the blood-spinal cord barrier at 16/24 targeted locations, as assessed by the extravasation of Evans blue dye. At 4 of these locations, opening was confirmed with minimal adverse effects observed through histology. Transmission measurements through excised vertebrae indicated a mean transmission of (47.0 ± 7.0 %) to the target. Conclusions: This study presents the first evidence of focused ultrasound-induced blood-spinal cord barrier opening in a large animal model, through the intact spine. This represents an important step towards clinical translation.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening

Fletcher¹,

Choi²,

Ogrodnik³

et al. 2020

Theranostics

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Overview of Therapeutic Ultrasound Applications and Safety Considerations: 2024 Update

Bader,

Padilla,

Haworth

et al. 2024

J of Ultrasound Medicine

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A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects (doi: 10.7863/jum.2012.31.4.623). This review serves as an update to the parent article, highlighting advances in therapeutic ultrasound over the past 12 years. In addition to general mechanisms for bioeffects produced by therapeutic ultrasound, current applications, and the pre‐clinical and clinical stages are outlined. An overview is provided for image guidance methods to monitor and assess treatment progress. Finally, other topics relevant for the translation of therapeutic ultrasound are discussed, including computational modeling, tissue‐mimicking phantoms, and quality assurance protocols.

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Focused Ultrasound-Induced Blood–Spinal Cord Barrier Opening Using Short-Burst Phase-Keying Exposures in Rats: A Parameter Study

Fletcher

Choi

Ramesh

et al. 2021

Ultrasound in Medicine & Biology

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Enhanced Detection of Bubble Emissions Through the Intact Spine for Monitoring Ultrasound-Mediated Blood-Spinal Cord Barrier Opening

Cited by 14 publications

References 44 publications

A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening

A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening

Overview of Therapeutic Ultrasound Applications and Safety Considerations: 2024 Update

Focused Ultrasound-Induced Blood–Spinal Cord Barrier Opening Using Short-Burst Phase-Keying Exposures in Rats: A Parameter Study

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