The targeting accuracy of a preclinical MRI‐guided focused ultrasound system

Ellens, Nicholas; Kobelevskiy, Ilya; Chau, Anthony; Waspe, Adam C.; Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

doi:10.1118/1.4903950

Cited by 22 publications

(13 citation statements)

References 25 publications

(25 reference statements)

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“…Due to the practical purposes, a small animal model would be most suitable for such a survival study. Dedicated preclinical focused ultrasound systems for small animals are available which can be used on 3T or 7T MRI systems, depending on local availability [ 36 – 38 ]. Treatment cells used in small animal studies should be reduced in size to a few mm since the sciatic nerves in rodents is on the order of 1 mm.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

et al. 2015

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PurposeUltrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system.MethodsVolumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining.ResultsAll targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation.ConclusionOur preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.

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Section: Discussionmentioning

confidence: 99%

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

et al. 2015

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“…For the treatments, the animals were positioned supine above an MRI-compatible three-axis positioning system, operationally similar to that described by Ellens et al 23 , that would mechanically position the ultrasound focus by moving a single-element, fixed focus transducer. The experimental setup is illustrated in Fig.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging

O’Reilly¹,

Jones²,

Barrett³

et al. 2017

Theranostics

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Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits.Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines. Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols. Animals received either a single treatment or four weekly treatments. Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects. The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment.Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere). There was a single adverse event in the chronic treatment group that resolved within 24 hrs. Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals. Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4 vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0). No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98) although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere.Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain. The treatment volumes and frequencies used are clinically relevant and indicate safety for clinical translation. Further study is warranted to determine if FUS has positive effects on naturally occurring amyloid pathology.

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“…The animals were placed supine on a sled above a 3‐axis positioning system, which was used to mechanically steer the transducer focus. The sled was designed to move between the positioning system, holding the US transducer, and the bore of a 7‐T MRI system (BioSpec 70/30 USR; Bruker, Billerica, MA) for treatment guidance.…”

Section: Methodsmentioning

confidence: 99%

Blood‐Brain Barrier Closure Time After Controlled Ultrasound‐Induced Opening Is Independent of Opening Volume

O’Reilly

Hough

Hynynen

2017

J of Ultrasound Medicine

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Objectives Microbubble-mediated focused ultrasound (US) opening of the blood-brain barrier (BBB) has shown promising results for the treatment of brain tumors and conditions such as Alzheimer disease. Practical clinical implementation of focused US treatments would aim to treat a substantial portion of the brain; thus, the safety of opening large volumes must be investigated. This study investigated whether the opened volume affects the time for the BBB to be restored after treatment. Methods Sprague Dawley rats (n = 5) received bilateral focused US treatments. One hemisphere received a single sonication, and the contralateral hemisphere was targeted with 4 overlapping foci. Contrast-enhanced T1-weighted magnetic resonance imaging was used to assess the integrity of the BBB at 0, 6, and 24 hours after focused US. Results At time 0, there was no significant difference in the mean enhancement between the single- and multi-point sonications (mean ± SD, 29.7% ± 18.4% versus 29.7% ± 24.1%; P = .9975). The mean cross-sectional area of the BBB opening resulting from the multi-point sonication was approximately 3.5-fold larger than that of the single-point case (14.2 ± 4.7 versus 4.1 ± 3.3 mm2; P < .0001). The opened volumes in 9 of 10 hemispheres were closed by 6 hours after focused US. The remaining treatment location had substantially reduced enhancement at 6 hours and was closed by 24 hours. Histologic analysis revealed small morphologic changes associated with this location. T2-weighted images at 6 and 24 hours showed no signs of edema. T2*-weighted images obtained at 6 hours also showed no signs hemorrhage in any animal. Conclusions The time for the BBB to close after focused US was independent of the opening volume on the time scale investigated. No differences in treatment effects were observable by magnetic resonance imaging follow-up between larger- and smaller-volume sonications, suggesting that larger-volume BBB opening can be performed safely.

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The targeting accuracy of a preclinical MRI‐guided focused ultrasound system

Abstract: The FUS system, as described, is capable of precise and accurate sonications. The largest source of error--misregistration of the coordinate systems of the scanner and ultrasound system--was addressed which reduced the error to 0.36 ± 0.14 mm, sufficient for many preclinical applications.

Cited by 22 publications

References 25 publications

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging

Blood‐Brain Barrier Closure Time After Controlled Ultrasound‐Induced Opening Is Independent of Opening Volume

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