Original contributionA feasibility study of in vivo T1ρ imaging of the intervertebral disc
Introduction
Low back pain is the most frequent cause of activity limitation for people under the age of 45 years in the United States [1]. Low back pain is frequently associated with degenerative disc disease (DDD), which is characterized by biochemical and morphological changes in the intervertebral disc [2], [3], [4]. The intervertebral disc is composed of three regions: (a) the nucleus pulposus; (b) the annulus fibrosus; and (c) cartilaginous end plates. The nucleus pulposus is a hydrated proteoglycan gel located in the center of the disc. It contains approximately 25% (dry weight) collagen and 50% (dry weight) proteoglycan [5]. The negatively charged proteoglycans in the nucleus are responsible for an internal swelling pressure, which provides compressive stiffness to the disc. The annulus is composed of 15–25 concentric lamellae [6] and is located on the periphery of the disc. It contains 67% (dry weight) collagen [5] and a low concentration of proteoglycans [7]. The collagen in the annulus resists the swelling pressure from the nucleus and provides tensile and shear strength. The end plates separate the disc from the bordering vertebral bone.
The process of disc degeneration is characterized by a loss of cellularity, degradation of the extracellular matrix (ECM) and, as a result, morphological changes and alterations in biomechanical properties. The most consistent chemical changes observed with aging are loss of proteoglycans and concomitant loss of water and disc pressure [8]. Secondary changes due to redistribution of tissue stress include fibrocartilage production with disorganization of the annular architecture and increases in type II collagen [9].
Together, degeneration-associated changes in the nucleus and the annulus are fundamental to the development of a number of spinal pathologies. For instance, changes in proteoglycan content within the nucleus lead to reduced imbibition of water, depressurization and flattening of the disc. The annulus may then bulge into the spinal canal and neural foramen. Disc height loss also results in narrowing of the spinal canal and unfolding of the ligamentum flavum, contributing directly to the development of spinal stenosis (which may result in constriction of spinal nerves or spinal cord). Herniation of the intervertebral disc leading to disc protrusion and extrusion can occur as a result of mechanical annular disruption and fissuring due to chronic nonphysiologic stress secondary to nuclear dehydration.
Various techniques have been proposed to assess the competence of the disc in vivo with particular emphasis on developing objective surgical indications. Radiographs are the first line of investigation in vertebral spine trauma but are of limited value in assessing suspected lumbar prolapsed intervertebral disc disease. While pain provocation using discography/CT discography [10], [11], [12] has been shown to improve the odds of a positive surgical outcome, there has been a reported high incidence of false positives [13] and there remains a significant number of severely degenerated discs that have been found to be asymptomatic [14].
Magnetic resonance imaging (MRI) has also been used as a noninvasive measure of disc degeneration visualizing early as well as more advanced changes. MRI allows the delineation of the annulus from the nucleus with high spatial resolution. Pfirrmann et al. [15] proposed a grading system for disc degeneration based on standard spin-echo sequences. With T2-weighted spin-echo imaging sequences, healthy intervertebral discs show a bright signal from the nucleus pulposus and a low signal from the annulus fibrosus. Disc degeneration is demonstrated by a change in the signal of the nucleus pulposus to give an irregular outline and a reduction in signal intensity. However, disc degeneration detected using MRI may not be associated with low back pain [16]. In the intervertebral disc, the uptake of Gd-DTPA enhancement has been observed clinically often in normal-appearing discs [17], and there is a high prevalence of disc degeneration in asymptomatic populations [18]. Stabler et al. [19] showed that a band-like contrast enhancement of the disc correlated with vascularization, often seen as a consequence of annular tears, and corresponded to pain, even in the absence of stenosis. Thus, the relationship between disc degeneration, MRI, and low back pain remains undefined.
In an effort to improve the capability of MR techniques to quantitatively assess disc degeneration, surrogate MR measures of tissue hydration, such as relaxation times (T1 and T2) and water diffusivity, are being studied. Investigators have demonstrated differences in T1 between mechanically loaded and unloaded disc specimens [20] as well as correlations between 1/T2 and both water and collagen content for disc specimens [7]. Since proteoglycan loss is an initiating factor of DDD, an in vivo imaging technique that reflects proteoglycan content would be ideal for the early detection of DDD. Quantitative T1ρ imaging probes the interaction between motionally restricted water molecules and their macromolecular environment; thus, the ECM in the intervertebral disc may potentially be investigated using these techniques. Previous studies have quantified T1ρ relaxation time in cartilage [21], [22], [23], [24], [25], [26] as well as in intervertebral disc specimens in vitro [27], [28], [29], [30] and have demonstrated a relationship between T1ρ relaxation and proteoglycan content [25], [31]. The purpose of this study was to test the feasibility of quantifying T1ρ relaxation time in phantoms and intervertebral discs of healthy volunteers using in vivo MRI at 3 T.
Section snippets
Phantom design
To examine the performance of the T1ρ pulse sequence, three phantoms with varying concentrations of agarose gel (50 ml; 1%, 2% and 4%; weight/volume) were constructed. Agarose (Sigma Aldrich, St. Louis, MO, USA) was chosen because it is known to exhibit decreasing T1ρ relaxation time with increasing agarose concentration, as well as T1ρ relaxation times similar to those of biologic tissues [32].
Human subjects
Eleven healthy volunteers (mean age=31.3 years; age range=23–60 years; gender: 5 females, 6 males)
Phantom
The median T1ρ values of the 1%, 2% and 4% agarose phantoms were 140.6, 83.8 and 56.0 ms, respectively. Fig. 4 illustrates line profiles of SNR and T1ρ in a phantom as a function of distance from the coil. The SNR decreases by approximately 50% from 6 to 10 cm from the surface of the coil. This range corresponds to the approximate position of the intervertebral disc during axial imaging. However, the T1ρ values are within 1 S.D. of the median T1ρ value of the phantom. The phantom
Discussion
In this study, a T1ρ spiral sequence was used to quantify T1ρ relaxation time in the intervertebral discs of healthy volunteers. This study demonstrates the feasibility of using spiral imaging at 3 T for in vivo T1ρ quantification of the intervertebral disc. The results indicate that the median T1ρ value of the nucleus is greater than that of the annulus, which is consistent with the results from a recent in vitro study by Regatte et al. [28]. The results also show highly significant
Acknowledgments
This research was funded by the National Institute of Health (Grant Nos. R21-AR51048 and R01-AG17762).
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