title: Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.
abstract: BACKGROUND
  The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo.
  
  
  OBJECTIVE
  To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo.
  
  
  METHODS
  Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading.
  
  
  METHODS
  Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density.
  
  
  RESULTS
  Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels.
  
  
  CONCLUSIONS
  Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance.
authors.affiliation: Rensselear Polytechnic Institute, 110 8th St, Troy, NY 12180, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gullbrand
authors.affiliation: Rensselear Polytechnic Institute, 110 8th St, Troy, NY 12180, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Peterson
authors.affiliation: Rensselear Polytechnic Institute, 110 8th St, Troy, NY 12180, USA.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mastropolo
authors.affiliation: Albany Medical College, 43 New Scotland Ave, Albany, NY 12208, USA.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Roberts
authors.affiliation: Albany Medical College, 43 New Scotland Ave, Albany, NY 12208, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Lawrence
authors.affiliation: Veterinary Specialties, 1641 Main St, Pattersonville, NY 12137, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glennon
authors.affiliation: Albany Medical College, 43 New Scotland Ave, Albany, NY 12208, USA.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: DiRisio
authors.affiliation: Rensselear Polytechnic Institute, 110 8th St, Troy, NY 12180, USA. Electronic address: ledete@rpi.edu.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Ledet
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018481:Convection; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007403:Intervertebral Disc / Q000187:drug effects*; D011817:Rabbits
chemical_list: D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA
keywords: Cartilage endplates; Convection; Disc nutrition; Intervertebral disc; Low rate mechanical loading; Nucleus pulposus