Axial T1ρ MRI as a diagnostic imaging modality to quantify proteoglycan concentration in degenerative disc disease

Abstract

Purpose The aim of the study was to investigate if axial T1ρ MR images had similar accuracy as established sagittal T1ρ MRI for the assessment of proteoglycan concentration and content in intervertebral degenerated discs (IDDs). Methods T1ρ and T2-weighted MR images of 12 intervertebral discs (IVDs) from 3 harvested human lumbar spines (levels L1–L2 to L5–S1) were grouped across their degenerative grade (Pfirrmann scores) and analyzed using a 3T MRI scanner in the axial and sagittal views. Post-processing of axial T1ρ-weighted images was performed using a Wiener filter. Median axial T1ρ values for traced regions of interest (ROIs) on color maps were compared against ROIs in the corresponding location in the sagittal plane of each disc. Assessment of sulfated glycosaminoglycans (GAGs) content was also performed. Results Comparison of post Wiener filtered mid-axial T1ρ values in the NP with corresponding mid-sagittal values revealed no statistical difference (P > 0.05). Higher axial T1ρ and biochemically measured GAGs content corresponded to a lower Pfirrmann grading of the IVDs. A strong association between the T1ρ values and the GAG contents was observed (r = 0.85, P = 0.0002). Conclusions The axial T1ρ methodology was validated against sagittal T1ρ providing an augmented spatial representation of IVD and can facilitate localization of focal degeneration within IVDs. T1ρ values provided a better granularity assessment of degenerative disc disease as it correlated with proteoglycan concentration. Thus, Wiener filtering is an effective tool for removing noise from T1ρ-weighted axial MR images.

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

“…Direct, in vivo evaluation of disc mechanical properties is possible using emerging technologies such as magnetic resonance elastography . Where direct evaluation is impossible, assessments of extracellular matrix composition and organization through biochemical and histological assays, or imaging (eg, MRI or contrast‐enhanced CT), represent important surrogates for mechanical function …”

“…For effective clinical translation it will be important to stratify patient cohorts, for example using sophisticated magnetic resonance imaging techniques [33][34][35][36][37] and quantification of circulating biomarkers 38 to select suitable candidates for treatment. The opportunity for cellbased therapy may be most appropriate at the early stage of the degenerative cascade, prior to the onset of advanced disc degeneration coupled with endplate calcification and extensive annular degeneration.…”

“…142,143 Where direct evaluation is impossible, assessments of extracellular matrix composition and organization through biochemical and histological assays, or imaging (eg, MRI or contrast-enhanced CT), represent important surrogates for mechanical function. [33][34][35][36][37] 7 | MAXIMIZING COMMERCIAL POTENTIAL Given the vast socio-economic costs associated with low back pain and the high costs of current treatment approaches, it would appear, superficially, to be straight forward to establish the commercial case for a new disc therapy, particularly one for which clinical safety and efficacy can be established. However, bringing a biological disc therapy to market is a long, complex and expensive process, and one that to date has been met with little success.…”

Critical aspects and challenges for intervertebral disc repair and regeneration—Harnessing advances in tissue engineering

“…Quantitative MRI using the relaxation times T1 and T2, the magnetization transfer ratio, and the apparent diffusion coefficient facilitates noninvasive assessment and diagnosis of changes including disc matrix composition (water, proteoglycan, and collagen), integrity (percent collagen denaturation), and biomechanics which have been shown to correlate strongly with disc tissue degeneration . Axial T1ρ MRI has been utilized to quantify proteoglycan concentrations which can be related to Pfirrmann grading, while chemical exchange saturation transfer (CEST) MRI has been employed for in vivo IVD pH level‐dependent imaging without the need for exogenous contrast agents . T2 mapping has been observed to be particularly sensitive to early and intermediate stage biochemical and mechanical degenerative changes compared with T1ρ in an ex vivo chymopapain digestion lapine model, while both parameters appear to be sensitive to advanced degenerative changes .…”

Influence of Age, BMI, Gender and Lumbar Level on T1ρ Magnetic Resonance Imaging of Lumbar Discs in Healthy Asymptomatic Adults

“…Early studies showed a significant correlation between the T1ρ relaxation time and the loss of proteoglycan molecules in cartilage [8]. In the spine, T1ρ relaxation times showed relevant correlations with the amount of proteoglycans in the extracellular matrix of the lumbar disc, with longer relaxation times indicating greater amounts of proteoglycans [7,9,10]. In addition, T1ρ relaxation times correlated significantly with the water content in the intervertebral lumbar disc [7].…”