In Vitro and In Vivo High-Intensity Focused Ultrasound Thrombolysis

Wright, Clinton S.; Hynynen, Kullervo; Goertz, David E.

doi:10.1097/rli.0b013e31823cc75c

Cited by 104 publications

(109 citation statements)

References 51 publications

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“…In FUS-induced BBB opening, 20,[32][33][34][35][36][37] sonothrombolysis, [38][39][40][41][42] and histotripsy 43,44 studies, correlations between the cavitation activity measured using a single-element passive cavitation detector (PCD) and treatment outcome have been reported. Moreover, microbubble emissions have been used to select treatment pressures 36 and modulate them in real-time between subsequent therapy pulses 35 during FUS-induced BBB opening.…”

Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. C 2015 American Association of Physicists in Medicine.

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Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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“…23,35,67 Inertial acoustic cavitation is the primary mechanism by which MRg-HIFU thrombolysis achieves clot disintegration. 6,11,33,45,57,71,73 Acoustic waves impart momentum to the fluid immediately surrounding the clot, creating microbubbles. 45,73 These microbubbles rapidly collapse along the clot surface, emitting shock waves and liquid jet speeds of more than 1 km/sec, which promote thrombolysis.…”

Section: Technology and Techniquesmentioning

confidence: 99%

“…1,2,9,68 In contrast, MRg-HIFU thrombolysis is an emerging stand-alone therapy for rapid transcranial clot disintegration in patients with ELVO and ICH and, according to in vitro and in vivo models, can potentially achieve recanalization and liquefaction rates of 63%-93% and > 95%, respectively. 10,25,30,45,50,51,73,75 Herein, we review the technological development, preclinical results, and future applications of MRg-HIFU thrombolysis.…”

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confidence: 99%

Magnetic resonance–guided, high-intensity focused ultrasound sonolysis: potential applications for stroke

Ilyas

Chen

Ding

et al. 2018

Neurosurgical Focus

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Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)—as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails—and intracerebral hemorrhage (ICH)—as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.

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“…The first clot was sonicated at 3 points along the clot surface and the second at 3 points along the beam axis for 5 mins at 500W with 0.5% duty cycle. [3] Postsonication, T 1 and T 2 images were taken of the clot samples. The second part of the porcine clot lysis testing involved creating an in-vivo clot in a 5 kg piglet.…”

Section: Porcine Clot Testingmentioning

confidence: 99%

Porcine pilot study of MRI-guided HIFU treatment for neonatal intraventricular hemorrhage (IVH)

Looi¹,

Waspe²,

Mougenot³

et al. 2012

AIP Conference Proceedings

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Abstract. Intraventricular hemorrhage (IVH) occurs in 15% of premature babies and 50% of IVH cases progress to posthemorrhagic ventricular dilation due to large blood clots forming in the ventricles. Existing treatments such as tissue plasminogen activator (tPA) and surgical intervention have severe side effects in paediatric patients that include excessive bleeding and complications. This study investigates the feasibility of MR-HIFU for sonothrombolysis of blood clots from IVH using natural acoustic windows, known as fontanelles, in the skulls of newborns. The study involved 2 elements: a phantom study to examine beam limitations and acoustic properties, and an in-vivo porcine study. A phantom skull was created from sample patient data and was used to analyze reachability of the Philips Sonavelle system. Acoustic measurements of the phantom (attenuation of 5-14 dB and speed of sound of 1722-2965 m/s) indicated the phantom effectively mimics neonatal skull bone. For the ex-vivo studies, a porcine clot was created and sonicated for 5 mins at 500W with a 0.5% duty cycle. For the in-vivo experiment, a vertex craniotomy was performed and porcine blood was injected into the lateral ventricle under ultrasound guidance. Sonication using the prior parameters induced cavitation and post-sonication T 1 and T 2 images verified clot lysis. Further H&E analysis showed no presence of blood in the ventricles. These positive results show that MR-HIFU has potential as a noninvasive tool for sonothrombolysis of neonatal IVH clots.

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In Vitro and In Vivo High-Intensity Focused Ultrasound Thrombolysis

Cited by 104 publications

References 51 publications

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Magnetic resonance–guided, high-intensity focused ultrasound sonolysis: potential applications for stroke

Porcine pilot study of MRI-guided HIFU treatment for neonatal intraventricular hemorrhage (IVH)

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