Age-related degeneration of lumbar intervertebral discs in rabbits revealed by deuterium oxide-assisted MRI

Abstract

Intervertebral disc (IVD) degeneration is associated with a loss of disc water content and change in biochemical composition of the disc. Rabbit is a frequently used model to evaluate the efficacy of therapeutics for disc degeneration. This study addresses whether rabbits undergo age-related disc degeneration, assessed using deuterium oxide-assisted magnetic resonance imaging (MRI) of the lumbar IVDs. The lumbar spines of adolescent, adult, and aged rabbits (6-36 months) were subjected to T2-weighted/short-tau inversion recovery (STIR) MRI scan along with water-deuterium oxide (H(2)O:D(2)O) dilutions. The total and maximum H(2)O:D(2)O index (HDi) of the lumbar IVDs were determined and compared between disc levels at different ages. Adolescent rabbit lumbar discs had similar total HDi, suggesting the hydration and biochemical composition was similar among the lumbar levels. With the use of H(2)O:D(2)O reference, the discs were shown to undergo continual decrease in signal with aging which non-calibrated measurement method could not reveal. The HDi decrease rate was higher at the caudal than cranial levels. This study provided in vivo evidence of age-related progressive disc degenerative change in rabbit lumbar discs, suggesting aged rabbits can be considered as a natural disc degeneration model in disc regeneration studies. However, it is important to select proper disc levels as intra-subject controls due to different rates of degenerative changes between caudal and cranial levels.