INTRODUCTION: The rabbit lumbar spine has been used as an animal model to study intervertebral disc (IVD) degeneration and to pre-clinically evaluate regenerative therapies. Magnetic resonance imaging (MRI) and histological assessments are essential endpoints for the evaluation of IVD degeneration and regeneration in a rabbit animal model. A ‘new standardized scoring system’ to evaluate disc degeneration in the rabbit model has recently been established. However, its correlation with MRI has not been reported.

   The purpose of this study was (1) to determine the effect of monosodium iodoacetate (MIA) injections into rabbit IVDs on IVD degeneration evaluated by the ‘new standardized scoring system’ and (2) to evaluate the correlation between MRI transverse relaxation time (T2) value and a standardized histopathology score.

METHODS: 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1-L2 to L4-L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1-L2: CA only; L2-L3: MIA 0.01 mg; L3-L4: MIA 0.1 mg; L4-L5: MIA 1.0 mg). Six rabbits were sacrificed at 2,4,8, and 12 weeks post-injection and processed for MRI (T2-mapping) and histological analyses. Blinded to the experiment, an observer analyzed the histological sections and graded them using the recently established standardized histopathology scoring system of rabbit IVD degeneration that involved seven subclasses (NP shape, area, cellularity and matrix condensation, AF/NP border appearance, AF morphology, and endplate (EP) sclerosis/thickening).

RESULTS SECTION: MRI assessment: Intradiscal injection of 1.0 mg (L4-L5 discs) significantly decreased T2-value compared to that of the CA control (L1-L2) discs (P<0.01). At week eight post-injection, the mean T2 value of MIA 1.0 mg (L4-L5) injected discs was significantly lower than that of MIA 0.01 mg (L2-L3) injected discs and CA control discs (P<0.05, P<0.01, respectively).

Histological assessment: The total histological scores of MIA 0.1 mg injected discs were significantly higher than those in the CA control discs at week 12 (P<0.01). The intradiscal injection of MIA 1.0 mg significantly increased the total histological scores compared to those of the CA control discs (week 2: P<0.05, week 4 to 12: P<0.01).

Correlation between MRI T2-values and histological scores: MRI T2-values of the whole disc negatively correlated with the total histological score (r=-0.83, P<0.01) (Fig. 1). Subclass analysis showed that MRI-T2 values significantly correlated with the NP shape (r=-0.66, P<0.01), NP area (r=-0.75, P<0.01), NP matrix (r=-0.81, P<0.01), NP cellularity (r=-0.67, P<0.01), AF/NP border (r=-0.78, P<0.01), AF (r=-0.80, P<0.01), and EP (r=-0.32, P<0.01). A strong correlation between whole disc MRI T2-values and histological scores was identified with four subclasses (AF and/or NP scores), while a weak correlation was found with the EP score.

DISCUSSION: A standardized histopathology scoring system showed that the intradiscal injection of MIA significantly affected the total histological score of rabbit disc degeneration throughout the experimental period. Our results also showed that MRI T2-values were strongly correlated with total histological grading score and subclass grading score, except for the weak correlation with the EP score.