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.