Differentiation of human cartilage degeneration by functional MRI mapping-an ex vivo study. 
To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage.  Upon IRB approval and written informed consent, 59 macroscopically intact osteochondral samples were obtained from the central lateral femoral condyles of patients undergoing total knee replacement.  Spatially resolved T1, T2, T2*, and T1ρ maps were generated prior to and during displacement-controlled quasi-static indentation loading to 405 μm (Δ1/2) and 810 μm (Δ1).  Upon manual segmentation, absolute qMRI parameters and loading-induced relative changes (δ1/2, δ1) were determined for the entire cartilage sample and distinct zones and regions.  Based on their histologically determined degeneration as quantified according to Mankin (Mankin sum scores [MSS], range 0-14), samples were dichotomised into intact (int; MSS 0-4, n = 35) and early degenerative (ed, MSS 5-8, n = 24).  For T1ρ, consistent loading-induced increases were found for δ1/2 and δ1.  Throughout the entire sample, increases in T1ρ were significantly higher in early degenerative than in intact samples (Δ1/2(ed) = 23.8 [q25 = 18.1, q75 = 29.0] %; Δ1/2(int) = 12.7 [q25 = 5.9, q75 = 19.5] %; p < 0.0005), according to Wilcoxon's signed-rank test).  Zonal and regional analysis revealed these changes to be most pronounced in the sub-pistonal area.  No significant degeneration-dependent loading-induced changes were found for T1, T2, or T2*.  Aberrant load-bearing of early degenerative cartilage may be detected using T1ρ mapping as a function of loading.  Hence, the diagnostic differentiation of intact versus early degenerative cartilage may allow the reliable identification of early and potentially reversible cartilage degeneration, thereby opening new opportunities for diagnosis and treatment of cartilage pathologies. •  T1ρ mapping of the cartilage response to loading allows the reliable identification of early degenerative changes ex vivo. •  Distinct response-to-loading patterns of cartilage tissue as assessed by functional MRI techniques are associated with biomechanical and histological tissue properties. •  Non-invasive functional MR imaging techniques may facilitate the more sensitive monitoring of therapeutic outcomes and treatment strategies.