Longitudinal In Vivo Assessment of Tibia Bone Porosity in T1DM Rabbits Using Ultrashort Echo Time MRI.

Abstract

BACKGROUND: Type 1 diabetes mellitus (T1DM) raises fracture risk. Longitudinal changes in cortical porosity during diabetes progression are unclear. PURPOSE: To assess, using ultra short echo time (UTE)-MRI for tibia cortical porosity and geometry changes in T1DM rabbit model, using micro-CT (&#x3bc;CT) and bone remodeling biomarkers as reference. STUDY TYPE: Longitudinal, animal model. ANIMAL MODEL: Twenty-eight male Japanese white rabbits (age: 8-10&#x2009;weeks, weight: 2.14&#x2009;&#xb1;&#x2009;0.24&#x2009;kg) randomized to diabetic (n&#x2009;=&#x2009;16) and control (n&#x2009;=&#x2009;12) subgroups. FIELD STRENGTH/SEQUENCE: 3&#x2009;T; 3D dual-echo UTE and 3D inversion recovery (IR)-UTE sequences. ASSESSMENT: UTE-MRI were performed at baseline and multiple timepoints. Porosity index (PI), suppression ratio (SR), and cortical thickness were assessed accordingly via the signal intensity (SI) at echo time (TE) at 2.2 and 0.032&#x2009;ms, SI of UTE to IR-UTE of TE at 0.032&#x2009;ms, and based on geometric modeling. &#x3bc;CT-derived porosity, pore diameter, and cortical thickness were conducted at week 24. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) analyzed bone remodeling markers. STATISTICAL TESTS: Group comparisons were made using t tests/Mann-Whitney U tests and repeated measures ANOVA. Spearman correlation coefficients (r) assessed the strength of the associations between PI and bone markers. A p value <&#x2009;0.05 was considered significant. RESULTS: 24-week T1DM rabbits had significantly UTE-MRI-measured higher cortical porosity (0.42&#x2009;&#xb1;&#x2009;0.05 vs. 0.32&#x2009;&#xb1;&#x2009;0.04) and lower cortical thickness (0.92&#x2009;&#xb1;&#x2009;0.11 vs. 1.40&#x2009;&#xb1;&#x2009;0.18) than the control group, consistent with &#x3bc;CT measurements. PI was significantly positively correlated with &#x3bc;CT-measured porosity and pore diameter (r&#x2009;=&#x2009;0.91, 0.69, respectively), while SR showed no correlation (r&#x2009;=&#x2009;-0.33, p&#x2009;=&#x2009;0.11; r&#x2009;=&#x2009;-0.25, p&#x2009;=&#x2009;0.25). PI increased significantly in T1DM rabbits from week 12 compared to the controls (0.35&#x2009;&#xb1;&#x2009;0.05 vs. 0.31&#x2009;&#xb1;&#x2009;0.04). The lower osteoblast and osteoclast-related cell numbers and expression were negatively correlated with PI in diabetic rabbits (r&#x2009;=&#x2009;-0.871 to -0.625). DATA CONCLUSION: UTE-MRI has the potential to longitudinally monitor and identify early reversible cortical porosity and geometric changes. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.