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Original Research |
1 Department of Clinical Research, Unit for MR Spectroscopy and Methodology,
University of Bern, CH-3010 Bern, Switzerland.
2 Department of Diagnostic, Interventional and Paediatric Radiology,
Inselspital, University of Bern, Bern, Switzerland.
3 Present address: Department of Radiology, Teikyo University Chiba Medical
Center, 3426-3 Anesaki, Ichihara, Chiba 299-0111, Japan.
4 Department of Orthopaedic Surgery, Inselspital, University of Bern, Bern,
Switzerland.
5 Tissue Engineering and Osteoarticular Research Unit, Institute of Pathology,
University of Bern, Bern, Switzerland.
6 Department of Biophysics, Molecular Imaging Center, National Institute of
Radiological Sciences, Chiba, Japan.
Received February 27, 2007;
accepted after revision May 31, 2007.
Address correspondence to A. Watanabe
(atsuyan1{at}pa2.so-net.ne.jp).
Abstract
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MATERIALS AND METHODS. Twenty-nine healthy volunteers (19 men, 10 women; age range, 20–44 years; mean age, 31.8 years) were studied, and axial T2 mapping was performed for the L3–L4, L4–L5, and L5–S1 intervertebral disks. Grading was performed using three classification systems for degenerative disks: our system using axial T2 mapping and two other conventional classification systems that focused on the signal intensity of the nucleus pulposus or the structural morphology in sagittal T2-weighted MR images. We analyzed the relationship between T2, which is known to correlate with change in composition of intervertebral disks, and degenerative grade determined using the three classification systems.
RESULTS. With axial T2 mapping, differences in T2 between grades I and II were smaller and those between grades II and III, and between grades III and IV, were larger than those with the other grading systems. The ratio of intervertebral disks classified as grade I was higher with the conventional classification systems than that with axial T2 mapping. In contrast, the ratio of intervertebral disks classified as grade II or III was higher with axial T2 mapping than that with the conventional classification systems.
CONCLUSION. Axial T2 mapping provides a more T2-based classification. The new system may be able to detect early degenerative changes before the conventional classification systems can.
Keywords: classification • degeneration • intervertebral disks • MRI • T2 mapping
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However, signal intensity cannot be measured in absolute terms because of the many arbitrary factors in signal detection and amplification. This may lead to interobserver bias, especially when observers classify relatively small changes in signal intensity as representative of early degeneration. MRI in the sagittal plane may make it possible to assess different levels of intervertebral disks and adjacent structures such as endplates, vertebral bodies, and bone spurs at one time; however, the sagittal plane limits the area of intervertebral disks in the field of view more than the axial plane does. The limited area of disks in the field of view may also limit detection of the deterioration in molecular composition or structural integrity observed in early degeneration. It has been suggested that early degenerative disks may exist before there is loss of signal intensity seen on T2-weighted MR images [3, 7]. Because degenerative intervertebral disks have been suggested as a potential cause of lower back pain [8, 9], development of a classification system that can detect degeneration at an earlier stage may help in understanding the relationship between degenerative disks and lower back pain.
Transverse relaxation time (T2) mapping has the potential to quantitatively evaluate deterioration of the molecular composition and structural integrity of intervertebral disks [10]. T2 is sensitive to water content and the arrangement of the collagen network structure and is also influenced by the dipolar interaction because of the anisotropic motion of water molecules in the collagen matrix [2, 5, 11–13]. A high T2 for the nucleus pulposus has been shown in healthy intervertebral disks; T2 decreases with the decrease of water content associated with disk degeneration [2, 5, 11]. In contrast, T2 for the annulus fibrosus is low in healthy intervertebral disks, and it increases with increased water content and loss of collagen anisotropy [5, 11]. As degeneration progresses, uniformity of T2 in both the nucleus pulposus and the annulus fibrosus will decrease and, finally, the distinction of signal intensity between the nucleus pulposus and the annulus fibrosus will be lost [14, 15]. Because changes in composition are observed early in intervertebral disk degeneration and progress as it advances [16], T2 mapping can be an ideal quantitative marker of degeneration in both the nucleus pulposus and the annulus fibrosus.
The aim of this study was to establish an MRI classification system for degenerative disks using axial T2 mapping, with a special focus on evaluating early degenerative intervertebral disks better than the conventional classification system, which uses sagittal T2-weighted MR images.
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MRI
MRI was performed at a fixed time in the afternoon for all volunteers to
minimize the possible influence of diurnal variation on T2 in intervertebral
disks. MRI was performed using a 3-T system (Trio, Siemens Medical Solutions)
with a dedicated spine coil. Sagittal T1- and T2-weighted imaging of the whole
lumbar spine was performed before T2 mapping to look for possible pathologic
changes such as degenerative intervertebral disks, herniated intervertebral
disks, spondylolysis, spinal canal stenosis, scoliosis, and facet
osteoarthritis and to select an axial slice passing through the center of the
disks.
T1-weighted scanning parameters were TR/TE of 609/13, 200 x 200 mm field of view, 3.0-mm section thickness, 0-mm interslice gap, 384 x 384 matrix, 1 excitation, and an echo-train length of 7. Total scanning time for this sequence was 3 minutes 24 seconds for 15 slices. T2-weighted imaging scanning parameters were 4,240/115, 200 x 200 mm field of view, 3.0-mm section thickness, 0-mm interslice gap, 384 x 384 matrix, 1 excitation, and echo-train length of 13. Total scanning time for this sequence was 4 minutes 14 seconds for 15 slices. T2 measurement with single-slice acquisition was performed at the selected slice by a set of morphologic images. A multi-spin-echo sequence was used for T2 measurement because it allows for T2 values in a suitable acquisition time. Multi-spin-echo scanning parameters were performed with TR/first-echo TE, last-echo TE, 1,500/10.3, 144.2; other parameters were 200 x 200 mm field of view, 3.0-mm slice thickness, 384 x 384 matrix, and 1 excitation. Total scanning time for this sequence was 9 minutes 41 seconds per disk.
Creating Color-Coded T2-Calculated Maps
T2-calculated maps were generated using MATLAB software (Mathworks) with a
monoexponential curve fit. For T2 measurement, the first echo per
multi-spin-echo sequence was excluded to minimize error from stimulated echoes
[18]. Using MATLAB, a
color-coded T2-calculated map of the intervertebral disks was segmented
manually by one author and was overlaid on the multi-spin-echo image with a TE
of 20.6 milliseconds. In the color scale, T2 was set from 20 to 80
milliseconds to distinguish nucleus pulposus and annulus fibrosus and to
visualize T2 change in nucleus pulposus and annulus fibrosus effectively on
the basis of previous experience. In the scale, blue represented areas of long
T2 and red represented areas of short T2.
Classification and Grading of Degenerative Intervertebral Disks
A classification system for degenerative intervertebral disks using axial
T2 mapping was developed with reference to conventional classification systems
developed by other authors [3,
4,
19]. In developing the new
system, particular emphasis was placed on change of T2 and inhomogeneity of T2
in the nucleus pulposus and annulus fibrosus, and the distinction between the
nucleus pulposus and annulus fibrosus. The classification system has a 4-grade
scale that is summarized in Table
1. Four representative color-coded T2 maps are shown in Figure
1A,
1B,
1C,
1D. Severely degenerated
intervertebral disks with collapsed disk spaces were excluded from assessment
because the new classification system was designed to classify relatively
early degenerative disks and we wanted to avoid possible volume averaging by
the endplate in the slice.
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Grading with Different Classification Systems
To investigate the ability of our classification system to classify
degenerative intervertebral disks, grading was performed using three
classification systems for degenerative disks: our system using axial T2
mapping, a conventional classification system focused on the signal intensity
of the nucleus pulposus on sagittal T2-weighted imaging MR images
[1–3,
6], and the classification
system reported by Pfirrmann et al.
[4], which focuses on signal
intensity and structural morphology of the nucleus pulposus on sagittal
T2-weighted imaging MR images. For comparison, the classification systems were
termed "axial T2 mapping," "conventional sagittal
T2-weighted imaging," and "Pfirrmann's sagittal T2-weighted
imaging," respectively.
In conventional sagittal T2-weighted imaging, intervertebral disks were classified as grade I if the signal intensity of the nucleus pulposus was normal, grade II if there was an intermediate loss of signal intensity in the nucleus pulposus, grade III if there was a marked loss of signal intensity in the nucleus pulposus, and grade IV if there was no signal. Pfirrmann's sagittal T2-weighted imaging is summarized in Table 2. Originally, this classification system had a 5-grade scale, and the difference between grades IV and V was the presence of a collapsed disk space in grade V. Because our classification system excluded severely degenerated disks with collapsed disk space from assessment, grade V was excluded from Pfirrmann's original classification system in this study.
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To establish degenerative grade, an axial T2 map was used for axial T2 mapping and T2-weighted sagittal images were used for the other systems. Three experienced observers independently graded the degenerative disks using the three classification systems twice with about 1 month between interpretations.
Data and Statistical Analysis
To assure the reliability of axial T2 mapping, intra- and interobserver
agreements were assessed using percentage of agreement and kappa statistics,
and findings were compared with the other systems. Results from the first
classification were used to evaluate interobserver agreement. Level of
agreement was assessed by kappa values following criteria reported by Landis
and Koch [20]: A negative
kappa value was interpreted as poor agreement, 0.00–0.20 as slight
agreement, 0.21–0.40 as fair agreement, 0.41–0.60 as moderate
agreement, 0.61–0.80 as substantial agreement, and greater than 0.81 as
almost perfect agreement. Statistical software (SPSS version 13; SPSS Inc.)
was used to calculate kappa values. A consensus classification with all
classification systems was performed by the three observers to obtain a
reference grade.
Relationships between degenerative grades using axial T2 mapping and subject age, disk level, presence or absence of disk herniation, and type of herniation were evaluated. The result of consensus classification was used for evaluation. The relationship between degenerative grades with axial T2 mapping and subject age was evaluated.
Consensus evaluation for disk herniation and type of herniation (if present) was performed by two observers. Disk herniation was classified into three types: protrusion, extrusion, and sequestration, using sagittal T1- and T2-weighted images [21, 22].
The T2 of the nucleus pulposus and annulus fibrosus in intervertebral disks was measured, and the relationship between T2 value and age was analyzed by regression analysis. In addition, we evaluated the relationship between T2 value and degenerative grade determined using the three classification systems. For T2 measurement, the region of interest (ROI) was drawn over the whole area of the nucleus pulposus and annulus fibrosus. For intervertebral disks whose distinction between nucleus pulposus and annulus fibrosus was unclear or lost, the ROI was drawn over the inner one third of the disk for the nucleus pulposus and the outer one third of the disk for the annulus fibrosus. To standardize the procedure, all measurements were performed by a single investigator. One-way analysis of variance was used for statistical analysis. Statistical significance was defined as p < 0.05. Statistical software (SPSS version 13) was used for analyses.
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Intraobserver and Interobserver Agreement and Consensus Classification
Intraobserver and interobserver agreements with the three classification
systems are summarized in Table
3. In both intraobserver and interobserver agreements, kappa
values for axial T2 mapping were interpreted as substantial to almost perfect
agreement, and the levels of agreement were almost the same as those of the
other classification systems.
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The consensus classification of systems is summarized in Table 4. The ratio of intervertebral disks classified as grade I was highest with conventional sagittal T2-weighted imaging, followed by the ratios in Pfirrmann's sagittal T2-weighted imaging and axial T2 mapping. In contrast, the ratio of intervertebral disks classified as grade II or III was highest with axial T2 mapping, followed by Pfirrmann's sagittal T2-weighted imaging and conventional sagittal T2-weighted imaging. No apparent difference was seen in the ratio of intervertebral disks classified as grade IV among systems.
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In a cadaveric study, histologic intervertebral disk alteration was found to begin at an early age [16, 23], with approximately 20% of teens having intervertebral disks with mild signs of degeneration; degeneration increased with age [17]. In our study, more than 20% of intervertebral disks in volunteers in their 20s had degeneration according to axial T2 mapping. This incidence rate is comparable with those of previous reports using histologic assessment, and the correlation between histologic and axial T2 mapping results may support the hypothesis that axial T2 mapping detects early degeneration better than the other classification systems.
The ability to detect early degeneration of intervertebral disks may contribute to better understanding of the progression of degeneration seen with age and other risk factors for degenerative disk disease. The ability to detect degeneration in the annulus fibrosus may contribute to investigation of the pathogenesis of lower back pain; primary sensory nerve endings have been found only in the outer annulus fibrosus, and the degeneration is likely to be responsible for disk-related pain. Use of axial T2 mapping may also contribute to evaluation of the effect of conservative and operative treatments for intervertebral disks, especially for new treatments such as nucleus pulposus replacement, gene therapy, and stem cell transplantation therapy [24–26].
Good to excellent intra- and interobserver agreements, comparable with those of the other classification systems, were observed in this study. Thus, axial T2 mapping has the potential to replace or supplement conventional classification systems in grading early degenerative intervertebral disks.
Our study has several limitations. First, because only healthy asymptomatic volunteers were included, the relationship between degenerative grade evaluated by axial T2 mapping and clinical symptoms such as lower back pain is still unclear. Further studies in patients with clinical symptoms, especially with disk-related pain, are needed to investigate correlations between degenerative grade as evaluated by our classification system and the presence and severity of clinical symptoms.
Second, neither biochemical nor histologic assessment of intervertebral disks was performed in this study, and therefore the relationship between degenerative grade evaluated by our classification system and the actual degenerative status of intervertebral disks is still unclear. However, our grading system is based on the T2 of intervertebral disks, which appears to correlate with biochemical alteration of degenerative disks reported in previous studies using extracted animal and cadaveric intervertebral disks. Thus, we conclude that our classification system correlates with the biochemical alteration of intervertebral disks to some degree. Further study using extracted disk samples is needed to validate the relationship between degenerative grade evaluated by axial T2 mapping and the actual degenerative status of an individual intervertebral disk.
Third, signal intensity of intervertebral disks as evaluated with T2-weighted imaging shows a diurnal variation due to change in the disk water content [27–29]; this is especially true in the nucleus pulposus. Because the T2 of the nucleus pulposus is thought to primarily reflect water concentration, diurnal variation may influence grading with our classification system. To minimize the influence of diurnal variation on T2 in intervertebral disks, we performed MRI at a fixed time in the afternoon for all volunteers; and physical laborers, who are thought to have substantially more load on the spine, were excluded from this study. However, because we did not perform additional studies to reveal diurnal change in T2, the influence of diurnal variation on grading of degenerative intervertebral disks remains unclear. Further study is needed to evaluate the influence of diurnal variation of T2 as obtained with our system.
Fourth, because the annulus fibrosus has highly organized collagen fibers with a lamellar structure, the annulus fibrosus can show regional variation in T2 due to orientation-dependent dipolar interaction. When collagen fibers are oriented 54.7° relative to the orientation of the static magnetic field (B0), the magic angle, regional T2 will be the longest [30]. Hardy [31] reported that regional variation in T2 due to orientation-dependent dipolar interaction could be observed in the annulus fibrosus when imaging in the axial plane is performed using an MR imager with a vertically directed magnetic field, but not with a horizontally directed magnetic field. Because the MR imager used for this study had a horizontally directed magnetic field, regional variation of T2 in the annulus fibrosus was not expected; in actuality, we did not observe apparent variation of T2 thought to be due to orientation-dependent dipolar interaction. However, special attention should be given to understanding regional variation in T2 when examining T2 in patients with malalignment of the spine.
Fifth, in this study, T2 measurements with high spatial resolution were performed separately for three disks, which required relatively long acquisition times. Clinically, the relatively long acquisition time for T2 measurement may make it difficult for the routine use of axial T2 mapping for detection of early degenerative intervertebral disks. However, reductions in spatial resolution or in the number of disks to be examined can reduce the total acquisition time. The most suitable spatial resolution for T2 measurement and number of disks to be examined should be selected for a specific study with axial T2 mapping in a clinically limited scanning time. Further study is needed to validate the clinical usefulness and relevance of axial T2 mapping.
In conclusion, our results show the potential of axial T2 mapping as a classification system for the detection of early degeneration in intervertebral disks. Axial T2 mapping can provide a useful noninvasive evaluation of matrix status in disks and can be a useful indicator of disk function.
Acknowledgments
We thank Jeanette Pfeiffer and the staff of the MRI division (Inselspital,
University of Bern) for their valuable technical assistance.
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