Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging

Abstract

Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration.

Figure 1.

Using CT and conventional MRI, 6 different parameters were scored in sheep: (1) loss of disc thickness (height); (2) new bone formation at the margins of the vertebral body (osteophytes); (3) calcifications in the annulus or nucleus; (4) penetration of the nucleus within and beyond the annulus; (5) reduction of T2 signal (indicating loss of water from the disc or loss of integrity of the extracellular matrix); and (6) Modic changes (Modic type 1, vascular development in the vertebral body, without trabecular damage or marrow changes; Modic type 2, changes in the bone marrow, with fatty replacement of the red, cellular marrow; and Modic type 3, visible fractures of the trabecular bone). A score from 0 to 3 is assigned to each of the 6 parameters according to defined characteristics. For example, a score of 2 is given for the parameter ‘osteophytes’ when pointed articular margins are identified. The 6 scores are summed to generate a combined imaging score (CIS), which is interpreted as no, moderate, intermediate, and severe intervertebral disc disease when it is less than 1, 2 to 4, 5 to 7, and greater than 7, respectively.

Figure 2.

Scores at T2 mapping. With T2 mapping, T2 relaxation times are transformed into a color map. Regions of interest were placed around the nucleus pulposus. As degeneration advances, color repartition in the annulus fibrosus (AF) and nucleus pulposus (NP) changes and, at the last stage, the distinction between the AF and NP is lost. Blue (high score) indicated areas of short T2 time and red (low score) depicted regions of long T2 time. Scores ranged from 1 to 4: 1, healthy intervertebral disc (IVD) with high and homogeneous T2 signal and a clear distinction between NP and AF; 2, mildly decreased and inhomogeneous T2 signal and less regular borders; 3, the T2 signal of the IVD is moderately reduced and inhomogeneous, and the distinction between the NP and the AF is not clear; and 4, the T2 signal of the IVD is severely decreased and inhomogeneous, and the distinction between the NP and the AF is lost.

Figure 3.

Changes in combined imaging score (CIS), T2 mapping score, and T2 time as a function of age (in years) according to intervertebral disc level. Blue, linear regression line; shaded area, 95% confidence interval for the mean. Slopes are larger for L6S1, illustrating more rapid degeneration at that level.

Figure 4.

Intradiscal calcifications were present at the ventral border of the annulus fibrosus (AF) when they were identified at the L6S1 level (white arrow, top). At other levels, they were always seen at the transitional zone between the AF and nucleus pulposus (NP; white arrows, bottom).

Figure 5.

Transitional vertebrae were found in 3 sheep. Transitional vertebrae are an anatomic variation of the last lumbar vertebra (L6) in which an enlarged transverse process (dotted white arrow) can form a joint or fusion with the sacrum (S1). In those 3 animals, the lumbosacral disc (white arrow) had a lower CIS score and higher T2 time than the L5L6 disc (white arrow). With T2 mapping, T2 relaxation times are transformed into a color map. Blue (high score) indicates areas of short T2 time, and red (low score) depicts regions of long T2 time.