Effect of short-term unloading on T2 relaxation time in the lumbar intervertebral disc--in vivo magnetic resonance imaging study at 3.0 tesla.

BACKGROUND CONTEXT: Diurnal changes in T2 values, indicative for changes in water content, have been reported in the lumbar intervertebral discs. However, data concerning short-term T2 changes are missing.
PURPOSE: The purpose of this study was to investigate the short-term effects of unloading on T2 values in lumbar intervertebral discs in vivo. STUDY
DESIGN: Experimental study with repeated measurements of lumbar discs T2 relaxation time during a period of 38 minutes of supine posture. PATIENT SAMPLE: Forty-one patients with acute or chronic low back pain (visual analog scale ≥3). OUTCOME MEASURES: T2 relaxation time in the intervertebral disc, lumbar lordosis angle, and intervertebral disc height.
METHODS: Forty-one patients (mean age, 41.6 years) were investigated in the supine position using a 3-tesla magnetic resonance system. Sagittal T2 mapping was performed immediately after unloading and after a mean delay of 38 minutes. No patient movement was allowed between the measurements. One region of interest (ROI) was manually placed in both the anterior and the posterior annulus fibrosus (AF) and three ROIs in the nucleus pulposus (NP).
RESULTS: There was a statistically significant decrease in the anterior NP (-2.7 ms; p<.05) and an increase in T2 values in the posterior AF (+3.5 ms; p<.001). Discs with initially low T2 values in the NP showed minor increase in the posterior AF (+1.6 ms; p<.05), whereas a major increase in the posterior AF was found in discs with initially high T2 values in the NP (+6.8 ms; p=.001). Patients examined in the morning showed no differences, but those investigated in the afternoon showed a decrease in the anterior NP (-5.3 ms; p<.05) and an increase in the posterior AF (+7.8 ms; p=.002). No significant differences were observed in other regions. Correlation analysis showed moderate correlations between the time of investigation and T2 changes in the posterior AF (r=0.46; p=.002).
CONCLUSIONS: A shift of water from the anterior to the posterior disc regions seems to occur after unloading the lumbar spine in the supine position. The clinical relevance of these changes needs to be investigated.

Introduction

Early observations of body height decreasing during the day have been attributed to the variable diurnal water content of the intervertebral disc compartments [1]. The interaction of compression during the day and the so-called swelling pressure of the disc generates a diurnal cycle of the squeezing out and reabsorption of water [2,3]. Eklund and Corlett [4] have shown that different types of loading lead to different degrees of height decrease. They have also shown that a rapid regain in height is achieved by lying down.

Magnetic resonance imaging (MRI) makes it possible to observe changes, in vivo, of disc water content, which is represented by changes of the transverse relaxation time T2 [5]. With the introduction of clinical high-field magnetic resonance (MR) scanners and the introduction of modern coil technology, particularly multielement coils, quantitative imaging sequences with high image resolution and high signal-to-noise ratio within clinically reasonable scan times have been developed [6,7]. Quantification of T2 relaxation times reflects matrix organization, collagen orientation, and hydration of cartilaginous tissues [8,9]. Short-term T2 value changes after unloading can be the result of changes in water content and changes in collagen fiber orientation [10-12].

However, only limited data are available to describe diurnal T2 changes in different compartments of the disc at a higher magnetic field strength [13,14]. To the best of our knowledge, no report has described the short-term changes in T2 relaxation times after unloading in the lumbar intervertebral disc at high field strength. The observation of short-term T2 changes could be of clinical value in terms of helping to distinguish between discs with different hydration states and maybe can help to identify painful discs. Furthermore, increased T2 fluctuation (water content changes) in the annulus fibrosus (AF) could indicate ultrastructural weakness that may precede disc herniation.

The purpose of our study was to investigate changes in T2 relaxation time in different compartments of the discs after unloading the lumbar spine in the supine position.

Materials and methods

Patient population

The study was approved by the ethics committee of the local medical university, and both oral and written informed consents were obtained from all patients. The study design used repeated measurements of lumbar disc T2 relaxation times during a period of 38 minutes of supine posture. We analyzed 205 lumbar intervertebral discs of 41 patients with a mean age of 41.6 years (standard deviation [SD], 10.5; range, 18–64). Inclusion criteria were the presence of low back pain (visual analog scale ≥3) with single or recurrent episodes in the previous 6 months and active participation in working life. Exclusion criteria were a body mass index greater than 30, radicular pain, neurologic deficits of the lower limb, previous spine surgery, contraindications for MRI, intervertebral disc herniation diagnosis in the last 2 years, or known scoliosis with more than a 10° Cobb angle.

Magnetic resonance imaging

All MR examinations were performed on a 3.0-tesla MR unit (Magnetom Tim Trio; Siemens Medical Solutions, Erlangen, Germany) with a gradient strength of 40 mT/m, using a dedicated eight-channel spine coil (3T Spine Matrix Coil; Siemens Medical Solutions, Erlangen, Germany).

Two serial T2 relaxation time measurements, with a target time delay of 30 to 45 minutes (mean, 38.4; SD, 9.1), were performed to assess changes in T2 relaxation time values after unloading the lumbar spine in the supine position. A time of 30 to 45 minutes was estimated to be a sufficient delay to observe T2 changes. This is based on the data of Eklund and Corlett [4] who reported a significant recovery of body height after 30 minutes of unloading. Between both T2 mapping sequences, morphologic and experimental sequences were performed. The patient was not allowed to move during this time.

The standard MR protocol of the spine included sagittal T1-weighted fast spin echo and sagittal, axial, and coronal T2-weighted fast spin echo sequences for morphologic MRI (for detailed parameters see Table 1). Those morphologic sequences represent a current standard for clinical spine MRI.

Table 1

Magnetic resonance parameters

Sequence	T1w-FSE sagittal	T2w-FSE sagittal	T2w-FSE transversal	T2w-FSE coronal	T2 map sagittal
Repetition time (ms)	900	4,400	5,080	4,500	1,200
Echo time (ms)	8.3	105	94	105	13.8–82.8
Field of view (mm)	300×300	280×280	210×210	280×280	220×220
Matrix	320×320	320×320	384×288	320×320	256×256
Voxel size (mm)	0.9×0.9×3	0.9×0.9×3	0.7×0.5×3	0.9×0.9×3	0.9×0.9×5
Slice thickness (mm)	3	3	3	3	5
Interslice gap (mm)	0.3	0.3	0.3	0.3	1
Number of slices	15	15	8×5	15	10
Echo trains/slice	111	20	18	20	—
Turbo factor	3	32	26	32	—
Examination time (min)	03:23	01:34	06:16	01:36	07:45

T1w-FSE, T1-weighted fast spin echo sequence; T2w-FSE, T2-weighted fast spin echo sequence.

Magnetic resonance parameters for morphologic imaging and T2 mapping sequences.

For T2 relaxation time measurements, a multiecho spin echo sequence with a repetition time of 1,200 ms, echo times 13.8, 27.6, 41.4, 55.2, 69.0, and 82.8 ms, a pixel matrix of 256×256, and a voxel size of 0.9×0.9×5 mm, was performed in the sagittal plane. This is the most common type of sequence for human in vivo spine T2 mapping and was used in a similar fashion also by other investigators [7,15,16]. T2 relaxation times were obtained from on-line reconstructed T2 maps using a pixelwise, monoexponential, nonnegative least-squares fit analysis (MapIt; Siemens Medical Solutions, Erlangen, Germany; Fig. 1).

Fig. 1

T2-weighted sagittal fast spin echo image is compared with a color-coded T2 map of intervertebral discs with regions of interest (ROIs). Each ROI measured 20% of the midline disc diameter in the sagittal plane. Region of interest 1 is interpreted as the anterior annulus fibrosus (AF), ROI 5 as the posterior AF, and ROIs 2 to 4 as the nucleus pulposus. The ROI numbering is illustrated in the L4/L5 disc.

All patients had a standard foam lower leg support (15 cm maximum height, decreasing caudally), which resulted in slight bending of the hip and knee joints. The five intervertebral discs (L1–S1) of the lumbar spine were analyzed. No obvious transitional vertebrae were detected.

Patients were investigated either in the morning (8 am to 12 pm; N=24) or afternoon (1–6 pm; N=17) to evaluate possible diurnal differences in short-term T2 changes. The total examination time per patient was 54 minutes and 28 seconds.

Image analysis

All image evaluations were performed by two radiologists in consensus, one with more than 6 years of experience and a special interest in musculoskeletal radiology and one with more than 15 years experience in musculoskeletal radiology. Five equally sized rectangular regions of interest (ROIs) on two adjacent central slices on sagittal T2 maps were measured manually. Each ROI measured 20% of the midline disc diameter in the sagittal plane. The most anterior and most posterior ROIs (ROI 1 and ROI 5) were interpreted as AF tissue, and the space in between (ROI 2, ROI 3, and ROI 4) was interpreted as nucleus pulposus (NP) tissue. The mean number of pixels for each ROI was 61.5 (SD, 9.7), which was calculated from 100 representative ROIs.

The lumbar lordosis angle (LLA) was evaluated on the corresponding central slices of the lowest echo images on the first and second T2 mapping sequence. The Cobb method was used for the LLA, which was defined as the angle between the superior end plates of L1 and S1. The LLA difference was calculated as the difference between the first and the second LLA measurements and thus represents changes between early and late unloading. Similarly, the disc space height was measured on both midsagittal echo images of the T2 mapping sequence anteriorly, posteriorly (both at the minimum distance of the bony rims), and in the center of the disc (point of maximum height). The parameter “relative posterior disc height increase” was calculated as the height increase posterior minus the height increase anterior in millimeters.

Intervertebral disc degeneration was assessed using the Pfirrmann grading system [17]. Of 205 discs, three discs were not eligible for ROI evaluation because of reduced disc space.

Statistical analysis

Statistical and graphical analyses were performed with SPSS 15.0 (SPSS, Inc., Chicago, IL, USA).

Paired two-tailed t tests were performed to observe changes between serial T2 measurements for the global and subgroup analyses (morning vs. afternoon and high vs. low basal NP T2) and the two measurements of LLA. To compare discs with high and low NP T2 values and patients with high and low LLA, the data set was split into tertiles (thirds) and the highest and lowest thirds were analyzed. Each value represents the mean of two slices per disc for the global analysis and the comparison of discs with different basal NP T2 values. To avoid multiplicity, the individual patient mean was calculated to compare differences between LLA tertiles and patients investigated at different times of the day. Pearson correlation analysis was performed to assess the associations between T2 change and LLA, LLA differences, disc height differences, and the time of investigation for those regions with significant changes. Similarly, the LLA changes were correlated to the relative posterior disc height increase on a patient-to-patient basis. Independent two-tailed t tests were performed to detect age differences between the subgroups. The mean of all five regions was calculated to observe global T2 changes within each single disc.

A p value lower than .05 was considered statistically significant.

Results

When analyzing T2 relaxation time changes between both sequential measurements in all patients and discs, the following results were found: there was a T2 value decrease in the anterior NP (ROI 2, −2.7 ms [−3.3% of absolute T2]; 95% confidence interval [95% CI], −5.2, −0.2; p<.05) and a T2 increase in the posterior AF (ROI 5, +3.5 ms [+5.9%]; 95% CI, +1.9, +5.2; p<.001), as shown in Fig. 2 and Table 2.

Fig. 2

Change in T2 values in milliseconds in different compartments of the disc from early to late unloading in the supine position. Each bar represents the mean of T2 changes in one 20% ROI from the anterior (blue) to the posterior AF (yellow). Error bars represent 95% confidence intervals. ROI, region of interest; AF, annulus fibrosus; NP, nucleus pulposus.

Table 2

Mean T2 values, lumbar lordosis angles, and disc space height

Measurement	Mean T2 (ms)	SD	95% CI		p Value
ROI 1 (anterior AF)
1st	40.3	11.5	38.7	41.9	.552
2nd	39.9	10.0	38.5	41.2
ROI 2 (anterior NP)
1st	81.9	35.8	76.9	86.9	.036∗
2nd	79.2	34.1	74.4	83.9
ROI 3 (central NP)
1st	104.9	45.5	98.6	111.3	.575
2nd	104.1	46.2	97.7	110.6
ROI 4 (posterior NP)
1st	107.7	48.0	101.0	114.4	.875
2nd	107.9	49.3	101.0	114.8
ROI 5 (posterior AF)
1st	59.4	21.2	56.4	62.3	<.001∗
2nd	62.9	24.1	59.5	66.2

SD, standard deviation; 95% CI, 95% confidence interval; ROI, region of interest; AF, annulus fibrosus; NP, nucleus pulposus; LLA, lumbar lordosis angle.

Comparison of T2 values, LLA, and disc space height between first and second measurements (ie, early vs. late unloading) in different disc compartments. p Values from the paired t tests are shown.

∗Marks statistically significant results.

Discs with low NP T2 values (lowest third) showed only a small T2 increase in the posterior AF (ROI 5, +1.6 ms [+3.5%]; 95% CI, +0.1, +2.1; p<.05), but there was a marked T2 increase in the posterior AF of discs with high NP T2 (ROI 5, +6.8 ms [+9.5%]; 95% CI, +2.8, +10.8; p=.001). The posterior AF T2 increase was significantly greater in high NP T2 discs (p=.01). Although there appeared to be a trend for decreased T2 values in the anterior NP (ROI 2), no significant differences were observed in other regions of the discs stratified as the “low” and “high” NP T2 groups (Fig. 3).

Fig. 3

T2 value changes in discs with low and high NP T2 values (lowest and highest third). Error bars represent 95% confidence intervals. ROI, region of interest; AF, annulus fibrosus; NP, nucleus pulposus.

Patients examined in the morning (N=24) showed no T2 differences between both T2 measurements in any of the regions. Those investigated in the afternoon (N=17) showed a T2 decrease in the anterior NP (ROI 2, −5.3 ms [−6.3%]; 95% CI, −10.6, −0.2; p<.05) and a T2 increase in the posterior AF (ROI 5, +7.8 ms [+13.2%]; 95% CI, +3.2, +12.3; p=.002) (Fig. 4).

Fig. 4

T2 value changes in patients investigated in the morning (8 am to 12 pm) and afternoon (1–6 pm). Error bars represent 95% confidence intervals. ROI, region of interest; AF, annulus fibrosus, NP, nucleus pulposus.

Patients stratified in groups of low and high LLAs (the highest and lowest third, respectively) demonstrated no significant T2 changes in any of the regions (Fig. 5). The mean LLA for the low- and high-LLA groups were 33.0° (95% CI, 30.5°, 35.5°; range, 25.9–40.1°) and 56.0° (95% CI, 52.9°, 59.1°; range 48.8–68.0°), respectively.

Fig. 5

T2 value changes in patients with high and low LLAs (lowest and highest third). Error bars represent 95% confidence intervals. ROI, region of interest; LLA, lumbar lordosis angle; AF, annulus fibrosus; NP, nucleus pulposus.

There was a significant decrease in mean LLA between the first and second measurements (−0.9° [−2.0%]; 95% CI, −1.7, −0.2; p=.01) as seen in Table 2. In concordance with that, the disc space height significantly increased posteriorly (+0.13 mm [+2.0%]; 95% CI, +0.22, +0.05; p=.002) and centrally (+0.12 mm [+1.1%]; 95% CI, +0.19, +0.06; p<.001) but not anteriorly (+0.6 mm; p=.28). The absolute disc height values can be seen in Table 2.

Correlation analysis showed no correlation between LLA and T2 changes in the anterior NP and the posterior AF (r=0.14 and r=−0.07), as well as no correlation between LLA difference and T2 changes (r=−0.19 for anterior NP and r=0.10 for posterior AF). There was a moderate positive correlation between the time of investigation and T2 changes in the posterior AF (r=0.46; p=.002; Fig. 6) but no correlation for the anterior NP (r=−0.18). The relative posterior disc height increase (posterior disc height increase minus anterior disc height increase) was not correlated with T2 changes in any region (all r<0.10) or the LLA difference (difference between first and second measurements; r=0.02; p=.90).

Fig. 6

Scatter/dot plot of the time of investigation and T2 value changes in the posterior annulus fibrosus. Pearson correlation analysis shows a moderate association.

The total T2 change in all ROIs (sum of changes of ROI 1 to ROI 5) was ±0.0 ms (95% CI, −1.4, +1.3) in the global per disc analysis. Similarly, none of the subgroups showed a significant global change between early and late unloading T2 measurements: low NP T2 (−0.1 ms; 95% CI, −1.3, +1.1); high NP T2 (−1.1 ms; 95% CI, −4.5, +2.4); low LLA (+0.6 ms; 95% CI, −2.7, +3.9); high LLA (+0.2 ms; 95% CI, −4.1, +4.5); morning (+0.1 ms; 95% CI, −2.8, +3.0); and afternoon (+0.2 ms; 95% CI, −2.5, +2.9) (Table 3).

Table 3

Total disc T2 value change

	N (discs)	Mean T2 change (ms)	SD	95% CI
All discs	202	±0.0	9.6	−1.4	+1.3
Low NP T2	67	+0.3	4.7	−0.9	+1.4
High NP T2	67	−1.0	13.3	−4.2	+2.2

SD, standard deviation; 95% CI, 95% confidence interval; NP, nucleus pulposus; LLA, lumbar lordosis angle.

Mean total disc T2 change (mean of all ROIs) in milliseconds.

Disc grading based on the Pfirrmann system revealed 113 (55%) Grade II, 70 (34%) Grade III, and 22 (11%) Grade IV discs. No discs were assigned to Grade I or V. The mean age was comparable in all subgroups (morning/afternoon: 43/40 years; low/high LLA: 38/41 years), except the NP T2 subgroups (low/high NP T2: 46/35 years [p<.001]).

Discussion

Our study represents the first in vivo quantitative T2 evaluation at 3.0 tesla, designed to investigate short-term T2 changes after unloading the lumbar intervertebral discs.

T2 relaxation time reflects collagen content and orientation as well as hydration of cartilaginous tissues [8,9]. Short-term T2 changes in the intervertebral disc can be interpreted as a variation in water content and a change in collagen fiber orientation; however, the change in water content seems to be dominant [10-12]. Thus, our results can be interpreted as demonstrating a fluid shift from the anterior to the posterior portions of the intervertebral disc during 38 minutes of unloading the spine in the supine position. This result can partly be explained by the biomechanical forces acting on the lumbar lordosis in the supine position. These biomechanical forces seem to underlie a variation between individuals, possibly influenced by the shape and lordosis of the lumbar spine [18,19] and the relative length and tension state of the iliopsoas and other muscles [20,21].

However, we could not show a direct correlation between LLA and T2 value changes. Clinical patient characteristics such as muscle shortening (iliopsoas), muscle weakness, or posture characteristics were not in the scope of this study.

The lumbar lordosis seems to be slightly straightened in the supine position compared with the standing position [22]. Slight hip flexion could increase this straightening and lead to a relative compression of the anterior disc portions in the supine position [23]. Our results may suggest that the average “compression state” of the intervertebral discs immediately before imaging was more similar to the state in the standing position (more lordosis) than that in the sitting position (less lordosis).

With the measurement of LLA in the morphologic images of the first and second T2 mapping sequence, we tried to assess gradual changes in LLA during the time in the magnet. Although there seems to be a slight decrease in LLA by about 1°, there was no correlation between the LLA differences and the observed T2 changes in the anterior NP and the posterior AF. In concordance to the LLA change between the T2 measurements, the disc height also changed, with an increase in disc space height posteriorly and centrally. However, there was no correlation between the relative disc height increase and the LLA difference. This could be the result of the reportedly low accuracy and reproducibility in those measurements, particularly when only small differences can be expected [24,25]. However, when averaging those numbers over a patient cohort, these changes become statistically detectable.

Compared with discs with low NP T2 values, the increase in the posterior AF is more prominent in discs with high NP T2 values. This could be explained by the higher water content in these discs [10,12]. Interestingly, our results suggest that also discs with lower NP T2 values experience water increases in the posterior AF after unloading in the supine position. Although not statistically significant, there appears to be a trend toward decreased T2 values in the anterior NP in both groups (Fig. 3). The comparison of discs investigated at different times of day showed relatively constant T2 values in the morning group, with no significant differences in any of the regions. In contrast, we observed pronounced changes in discs investigated in the afternoon. One possible interpretation for this is a higher intradiscal pressure of the NP in the morning hours, which does not allow major intradiscal fluid shifts. One could imagine the disc as a fully expanded air mattress, which is not easy to bring out of shape. However, a lower intradiscal pressure in the afternoon could ease fluid transfer within the intervertebral disc (“only partly filled air mattress”). Wilke et al. [26] demonstrated that, after 7 hours in the lying position, the intradiscal pressure increased to 240% of its value before bed rest. Interestingly, discs with high T2 (high water content and high intradiscal pressure) show the greatest T2 changes. The lower water content and decreased capability of overnight water reimbibition in degenerative discs could be an explanation for this. It might be that the majority of the morning versus afternoon difference is because of T2 changes in high T2 discs. However, we could not provide evidence for this in our study, because the limited sample size does not allow a subgroup of subgroup analysis.

Eklund and Corlett [4] used body height measurements in healthy volunteers to investigate short-term changes in disc water content indirectly. Although they described a rapid regain in body height after lying down, a significant increase in total disc water content, measured indirectly by T2 relaxation time, was not observed in our patients. The mean of T2 value changes within all ROIs of all discs was near zero in both the pooled analysis and the subgroups. Our results suggest a fluid shift within the disc rather than a global change in disc water content for this short period of time. Although Ludescher et al. [14] did not investigate short-term, but rather, diurnal T2 changes, they also found indirect evidence of fluid shifts within different disc compartments. If the lack of total disc short-term T2 increases is the result of examining only patients, or the result of a relatively short delay between measurements, it must be elucidated in future studies.

The results of our study warrant future studies in this field. In particular, longitudinal studies comparing short-term T2 changes with clinical parameters, such as pain and function, would be of interest. The observed T2 changes in the posterior AF (ROI 5) and its relationship to future development of disc herniation could be of clinical relevance. One could imagine that increased T2 fluctuation (water content changes) in the AF could indicate ultrastructural weakness, which may precede disc herniation.

One has to keep in mind, however, that the observed mean changes in our study are the net effects of the global sample and subsamples, whereas single patient and disc showed marked interindividual variation in results.

The general limitations of our investigation involve the lack of clinical patient data and healthy control subjects. Moreover, no histologic workup was performed in our study because no surgical procedures were performed in our patients. Because of the descriptive nature of our investigation, multiple statistical testing was performed.

In conclusion, our method of segmental quantitative T2 evaluation seems to be able to detect short-term changes in water content in different compartments of the lumbar intervertebral disc. To the best of our knowledge, this is the first report of this kind in vivo. The observed changes in water content seem to be pronounced in the afternoon and appear to be related to the time of investigation, particularly in the posterior AF. Although we observed more distinct changes in discs with higher water content compared with those with lower water content, the clinical impact of short-term T2 value changes must be determined in future studies. Longitudinal studies comparing short-term T2 changes with clinical parameters and future development of disc herniation are warranted.