Ultrashort Echo Time Magnetization Transfer MRI for Cortical Bone Collagen Assessment and Its Association With Mineralization in Type 1 Diabetes

BACKGROUND: Type 1 diabetes mellitus (T1DM) increases fracture risk beyond bone mineral density (BMD), implicating matrix quality. Whether ultrashort echo time magnetization transfer (UTE-MT) MRI can track collagen alterations in T1DM and their associations with mineralization is unknown. PURPOSE: To evaluate UTE-MT-derived magnetization transfer ratio (MTR) for monitoring in vivo cortical collagen alterations in T1DM and to investigate its associations with mineralization and multiscale bone properties. STUDY TYPE: Longitudinal animal model. ANIMAL MODEL: 18 male New Zealand white rabbits (Age: 5-6 months) randomized to diabetic (n = 12) and control (n = 6) groups. FIELD STRENGTH/SEQUENCE: 3 T/3D gradient-echo UTE-MT sequence. ASSESSMENT: UTE-MT MRI was performed at baseline (week 0) and weeks 12, 16, and 20 post-alloxan induction. Cortical MTR was calculated from paired MT-on/off images and quantified over cortical regions of interest. Reference measurements at the terminal time point (week 20) included micro-CT (cortical porosity [CtPo]), histomorphometry (mineral apposition rate [MAR], bone formation rate [BFR/BS]), fourier transform infrared spectroscopy (FT-IR) (collagen cross-linking), liquid chromatography-tandem mass spectrometry (LC-MS/MS) (hydroxyproline [Hyp]), histology (collagen maturation), and mechanical testing. STATISTICAL TESTS: The t-tests/Mann-Whitney U for endpoint cross-sectional comparisons, linear mixed-effects model for longitudinal MTR, Pearson correlations (r) for associations; p < 0.05 was considered significant. RESULTS: Cortical MTR declined in T1DM rabbits, becoming significantly lower than controls at week 12 and lowest at week 20. At termination, T1DM group demonstrated significantly higher CtPo (1.345 ± 0.270% vs. 0.591 ± 0.233%), elevated NE-xLR, reduced MAR, BFR/BS, Hyp, ECR, and collagen maturation (1.705 ± 0.548 vs. 5.474 ± 1.455). Mechanical properties (elastic modulus [E], yield strength [YS], toughness) were significantly lower in the T1DM group, with reductions of 44.1%, 35.2%, and 63.2% relative to controls, respectively. MTR at week 20 correlated positively with Hyp, ECR, collagen maturation, mineralization, and mechanical parameters (r = 0.562 to 0.900), and negatively with NE-xLR via partial correlation (r = -0.616) and CtPo (r = -0.826). DATA CONCLUSIONS: UTE-MT-derived MTR enables in vivo tracking of cortical collagen dynamics in T1DM. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.