Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

Spinal cord injury(SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound(MRg FUS) as a non...

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Published inNeural regeneration research Vol. 12; no. 12; pp. 2045 - 2049
Main Authors Payne, Allison, Hawryluk, Gregory, Anzai, Yoshimi, Odéen, Henrik, Ostlie, Megan, Reichert, Ethan, Stump, Amanda, Minoshima, Satoshi, Cross, Donna
Format Journal Article
LanguageEnglish
Published India Wolters Kluwer India Pvt. Ltd 01.12.2017
Medknow Publications and Media Pvt. Ltd
Medknow Publications & Media Pvt. Ltd
Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, USA%Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA
Medknow Publications & Media Pvt Ltd
Wolters Kluwer Medknow Publications
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Summary:Spinal cord injury(SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound(MRg FUS) as a non-invasive approach to increase permeability in the blood-spinal cord barrier(BSCB). We hypothesize that localized, controlled sonoporation of the BSCB by MRg FUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRg FUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRg FUS blood spinal cord barrier opening. Then, in normal rats, MRg FUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles.
Bibliography:Spinal cord injury(SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound(MRg FUS) as a non-invasive approach to increase permeability in the blood-spinal cord barrier(BSCB). We hypothesize that localized, controlled sonoporation of the BSCB by MRg FUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRg FUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRg FUS blood spinal cord barrier opening. Then, in normal rats, MRg FUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles.
focused ultrasound; spinal cord; magnetic resonance imaging; contrast-enhanced; blood-spinalcord barrier
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Author contributions: All authors contributed to manuscript preparation and editing. DJC contributed to overall study design, imaging, spinal cord injury, evaluation of histology. AHP and HO were in charge of MRgFUS, imaging, image analysis. GWH contributed to expertise in spinal cord and spinal cord injury, evaluation of histology. YA and SM was responsible for imaging and image analysis. MAO, ECR and AJS contributed to imaging, neurological function, histology, data analysis.
ISSN:1673-5374
1876-7958
DOI:10.4103/1673-5374.221162