Intervertebral disc (IVD) degeneration is characterized by progressive changes in matrix orientation and composition [1]. Therefore, in-vivo measurements of IVD mechanical properties, which are a product of both structure and composition, could provide an objective classification of the degeneration process. Magnetic resonance elastography (MRE) is a non-invasive imaging technique that allows the measurement of shear properties by tracking wave propagation through soft tissues and has been used to aid diagnosis of cardiac and liver diseases associated with increased tissue stiffness [2,3]. This study aimed to (i) investigate the relationship between in-vivo shear stiffness (m) and IVD degeneration and its reproducibility and (ii) characterize how the diurnal change in IVD height (due to daily creep) influence in-vivo shear stiffnessThirty nine subjects with no prior history of chronic low back pain (Ages: 20-65) were scanned in the morning (AM) and in the evening (PM) with an average of 6.4 hours between scans. All protocols were approved by institutional review board. All images (Sag: T2, Ax: T1 & MRE) were obtained using a 3T MRI scanner (Tim Trio, Siemens). For MRE scans, vibrations were applied to the lower back via a pneumatic driver system and the in- and through- plane displacements were encoded. The first harmonics of the displacement fields were processed using a multimodel direct inversion (MMDI) algorithm to estimate the weighted stiffness of the IVD. A 4x4 median filter was applied to all stiffness maps and the nucleus pulposus (NP) region was traced on the T1 axial scan and copied on the stiffness map to report the mean shear stiffness. Frequency Response: The L34 IVD of five subjects was scanned at three different excitation frequencies (60, 80 and 100Hz). For the reproducibility and degeneration studies MRE vibrations were applied at 80Hz. Reproducibility: The L34 IVD of eight subjects was scanned three times, with the subject and driver repositioned in between scans. The average NP shear stiffness from scans 1 through 3 was compared with repeated measures ANOVA. Diurnal & Degeneration: Five scorers (three radiologists and 2 neurosurgeons) were blinded and assigned a Pfirrmann degeneration score three times to every IVD. The average of the 15 scores per IVD was rounded and assigned to each IVD. Stiffness values were not normally distributed and diurnal stiffness values were log transformed to obtain a normal distribution. A one-way ANOVA was used to determine if there were significant differences in NP shear stiffness between the different degrees of IVD degeneration and a paired t-test compared AM and PM stiffness. The effect of age was assessed via a Spearman correlation. Frequency Response: There was a linear increase in NP shear stiffness with frequency (Fig 1). 80Hz was chosen because it gave an NP shear stiffness (12.2±4.1 kPa) similar to the rheologically derived NP shear modulus (7.4±11.6 kPa)[4]. Reproducibility: There were no significant differences between the NP shear stiffness between the three repeat scans (Fig 2). Diurnal & Degeneration: There was a significant decrease in NP shear stiffness between a Pfirrmann degeneration grade 2 and grade 4 &5 (Fig. 3). There was a weak correlation between NP shear stiffness and age for levels L23 (R2=0.156, p=0.004) and L45 (R2=0.167, p=0.0002) and no correlations for L12, L34 & L5S1. No differences were observed between AM and PM shear stiffness (Table 1). Results suggest that MRE analysis can provide a repeatable measurement of NP stiffness that may serve as an objective biomarker of the degeneration process that is independent of age. The magnitude of the shear stiffness of non-degenerated NP tissue measured in this study is similar to previous in-vitro shear stiffness measurements [4]; and confirms in-vitro MRE findings that shear stiffness is reduced with degeneration [5]. Due to the non-linear creep response, ~50-60% of the daily height loss was expected between scans; however this did not induce a detectable difference in NP shear stiffness. Underestimation of the shear stiffness of the annulus fibrosus (AF) was due to insufficient wave numbers generated withi n this region because of its high shear stiffness. However, this does allow a visualization of the NP area which may provide a measure of NP inhomogeneity.MRE analysis of IVD shear stiffness allows an objective and non-invasive assessment of IVD degeneration that is independent of age.