title: A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles.
abstract: BACKGROUND
  The most commonly used animal models of spinal cord injury (SCI) involve surgical exposure of the dorsal spinal cord followed by transection, contusion or compression. This high level of invasiveness often requires significant post-operative care and can limit post-operative imaging, as the surgical incision site can interfere with coil placement for magnetic resonance imaging (MRI) during the acute phase of SCI. While these models are considered to be similar to human SCI, they do not occur in a closed vertebral system as do the majority of human injuries.
  
  
  METHODS
  Here we describe a novel, non-surgical model of SCI in the rat using MR-guided focused ultrasound (FUS) in combination with intravenous injection of microbubbles, applied to the cervical spinal cord.
  
  
  RESULTS
  The injury was well-tolerated and resulted in cervical spinal cord damage in 60% of the animals. The area of Gd-enhancement immediately post-FUS and area of signal abnormality at 24h were correlated with the degree of injury. The extent of injury was easily visualized with T2-weighted MRI and was confirmed using histology.
  
  
  CONCLUSIONS
  Pathology was similar to that seen in other rat models of direct spinal cord contusion and compression. Unlike these methods, FUS is non-surgical and has lower mortality than seen in other models of cervical SCI.
  
  
  CONCLUSIONS
  We developed a novel model of SCI which was non-surgical, well-tolerated, localized, and replicated the pathology seen in other models of SCI.
authors: Department of Medical Biophysics, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada. Electronic address: wendy.oakden@utoronto.ca.
authors: Wendy
authors: W
authors: Oakden
authors: Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street W, Hamilton, ON L8S 4L8, Canada. Electronic address: kwiecien@mcmaster.ca.
authors: Jacek M
authors: JM
authors: Kwiecien
authors: Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: moreilly@sri.utoronto.ca.
authors: Meaghan A
authors: MA
authors: O'Reilly
authors: Department of Medical Biophysics, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada. Electronic address: elake@sri.utoronto.ca.
authors: Evelyn M R
authors: EM
authors: Lake
authors: TECHNA Institute, University Health Network, 124-100 College Street, Toronto, ON M5G 1P5, Canada; Department of Surgery, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada. Electronic address: margarete.akens@rmp.uhn.ca.
authors: Margarete K
authors: MK
authors: Akens
authors: Brain Sciences Research Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada. Electronic address: isabelle.aubert@sri.utoronto.ca.
authors: Isabelle
authors: I
authors: Aubert
authors: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Division of Orthopaedics, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: cari.whyne@sunnybrook.ca.
authors: Cari
authors: C
authors: Whyne
authors: Department of Surgery, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada; Division of Orthopaedics, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: joel.finkelstein@sunnybrook.ca.
authors: Joel
authors: J
authors: Finkelstein
authors: Department of Medical Biophysics, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada; Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: khynynen@sri.utoronto.ca.
authors: Kullervo
authors: K
authors: Hynynen
authors: Department of Medical Biophysics, University of Toronto, 172 St George Street, Toronto, ON M5R 0A3, Canada; Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada. Electronic address: stanisz@sri.utoronto.ca.
authors: Greg J
authors: GJ
authors: Stanisz
mesh_terms: D000208:Acute Disease; D000818:Animals; D066193:Cervical Cord / Q000293:injuries* / Q000473:pathology; D002908:Chronic Disease; D003287:Contrast Media; D004195:Disease Models, Animal; D005682:Gadolinium; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D045423:Microbubbles; D009043:Motor Activity; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D005682:Gadolinium
keywords: Focused ultrasound; Histopathology; Magnetic resonance imaging; Microbubbles; Spinal cord; Spinal cord injury