In Vivo 3.0-Tesla Magnetic Resonance T1ρ and T2 Relaxation Mapping in Subjects With Intervertebral Disc Degeneration and Clinical Symptoms

Intervertebral disc degeneration (IVDD) is the leading cause of pain and disability in adults in the United States (1). The rate of disc degeneration increases with age (2), and IVDD is responsible for over 90% of adult spinal surgical procedures (3). Studies have demonstrated a relationship between disc degeneration and low back pain (4–6); however, the mechanisms for its causes are still under investigation. IVDD is characterized by biochemical and morphologic changes in the nucleus pulposus and annulus fibrosus. The nucleus pulposus is a hydrated gel containing approximately 25% (dry weight) collagen and 50% (dry weight) proteoglycan (PG) (7). The annulus fibrosis is composed of 15–25 concentric lamellae (8) and is located on the periphery of the disc. It contains 67% (dry weight) collagen (7) and a low concentration of proteoglycans (9). Early signs of disc degeneration are manifested by biochemical changes (proteoglycan loss, dehydration, and collagen degradation) that eventually lead to morphologic degradation in the vertebral bodies, endplates, and facet joints. The most significant biochemical changes that occur in early IVDD include a loss of proteoglycans (2). During the course of IVDD, small degraded fragments of molecules can seep from the tissue, resulting in a loss of osmotic pressure and hydration (2), thus altering mechanical properties. While not as pronounced, changes to the collagen type and organization are also prevalent in IVDD (2). During disc degeneration, type I collagen fibers replace the type II collagen fibers in the annulus (10), thus altering the tensile properties of the tissue. In the later stages of IVDD, morphologic changes including a loss of disc height, disc herniation, annular tears, and radial bulging are evident (10). Thus, IVDD is a complex and multifaceted process whose biochemical and morphologic changes adversely affect the mechanical and functional integrity of the disc. It is difficult to compare the clinical symptoms experienced by various individuals with IVDD since pain and physical ability are subjective by nature, with varying tolerances and expectations between individuals. A number of questionnaires, including the SF-36 Health Survey (11) and Oswestry Disability Index (O.D.I.) (12), aim to quantify the severity of physical limitation and disability, thus providing a standardized and comparable measure of clinical symptoms. These questionnaires have been shown to provide reliable quantitative scoring systems in previous studies (13,14). The SF-36 and O.D.I. questionnaires have been widely used in patient studies, and their reliability and the validity have been studied extensively (13,14). Despite the high prevalence of IVDD worldwide, diagnosis in the early stages of symptomatic disease is elusive in clinical practice. The traditional methods for imaging disc degeneration, including radiography, MRI, and CT, are limited to depicting late-stage, gross morphologic changes. Ideally, a method that detects the initial biochemical changes in disc degeneration would be valuable in preventing disease progression. Such a method would improve diagnostic capabilities and enable preventive measures to be taken at the early stages of the disease. MRI has been widely used to detect IVDD because it is noninvasive, provides superior soft tissue contrast, and can be used to assess tissue hydration. To date, MRI has been mostly used for morphologic, qualitative assessment of IVDD. 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 exhibit a bright signal from the nucleus pulposus and a low signal from the annulus fibrosus. While the Pfirrmann grading system provides a semi-quantitative evaluation of disc degeneration, which is beneficial for morphologic evaluation, MRI relaxation time measurements offer a quantitative assessment of disc composition. Quantitative relaxation time measurements are beneficial in that they compute a tissue material property, which should be scanner independent (16). In addition, quantitative techniques are able to detect subtle differences in tissue composition that may not be apparent with qualitative or semiquantitative measurements. MRI T2 relaxation time is a quantitative parameter that is sensitive to changes in collagen and water content in cartilage (17) and in the intervertebral disc (18). Studies have shown that T2 decreases with disc degeneration (19–21). Perry et al. (20) measured T2 in five subjects, using an FSE sequence, and reported that the average T2 values were greater in normal discs as compared to those graded as Pfirrmann grade III or IV. Karakida et al. (22) investigated diurnal changes in the disc by measuring T2 in the morning and evening and reported that degenerative discs had lower T2 than healthy discs at both time points. These studies demonstrate that T2 may be a noninvasive biomarker for IVDD that is sensitive to changes in collagen and hydration in early disc degeneration. Recent studies have proposed that MRI T1ρ is associated with loss of macromolecules (23), which is an initiating factor in IVDD. T1ρ imaging, which probes the interaction between water molecules and their macromolecular environment, has the potential to identify early biochemical changes in the intervertebral disc. Recent in vitro studies have reported correlations between T1ρ and glycosaminoglycan content (23) and have demonstrated a relationship between T1ρ and disc mechanical properties (24), suggesting that T1ρ may be sensitive to early biochemical changes in disc degeneration. In vivo studies have demonstrated differences in mean T1ρ values between the nucleus and the annulus (25) and have shown a correlation between T1ρ and degenerative grade in an asymptomatic population at 1.5 T (26), thus demonstrating the feasibility of quantifying T1ρ in human subjects. The purpose of this study was to (1) determine the correlation between T1ρ and T2 and degenerative grade in intervertebral discs using in vivo MRI at 3 T, and to (2) determine the association between T1ρ and T2 and clinical findings as quantified by the SF-36 questionnaire and O.D.I.