The objective of the study was to evaluate tibial cartilage thickness (TCT), T1ρ and T2 values within both loaded and baseline configurations in a cadaveric knee model using a 3D bone based tibial coordinate system. Ten intact cadaveric knees were mounted into an magnetic resonance imaging (MRI) compatible loading device. Morphologic and quantitative MRI (qMRI) images were acquired with the knee in a baseline configuration and after application of 50% body weight. The morphologic images were evaluated for cartilage degeneration using a modified Noyes scoring system. A 3D bone-based tibial coordinate system was utilized to evaluate regional changes of tibial T1ρ, T2, and cartilage thickness values among regions covered and uncovered by the meniscus. Inter-regional differences in medial and lateral MRI outcomes were found between loaded and baseline configurations. Cartilage regions covered by the meniscus demonstrated disparate qMRI and TCT results as compared to cartilage regions not covered by the meniscus. The regions covered by meniscus experienced a ~3.5%, ~0.5%, and ~5.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT, respectively, in both compartments while regions not covered by the meniscus experienced larger reductions of ~10%, ~2%, and ~10.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT (p < 0.05, lateral compartment only), respectively, in both compartments. T1ρ and T2 decreases following application of 50% body weight load were substantially larger in the tibial regions with modified Noyes grade 3 (n = 2) compared to either healthy regions (n = 85, p < 0.0.003) or regions with modified Noyes grade 2 (n = 13, p < 0.004). Interregional differences in MRI outcomes reflect variations in structure and function, and largely followed a pattern in cartilage regions that were covered or not covered by the meniscus. Results of the current study suggest that ΔT1ρ and ΔT2 values may be sensitive to superficial fissuring, more than baseline or loaded T1ρ or T2 values, or TCT alone, however future studies with additional specimens, with greater variability in OA grade distribution, may further emphasize the current findings.