摘要
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.
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.
基金
supported by the University of Utah Radiology
Neuroscience Initiative Pilot grant
the Department of Neurosurgery pilot fund
