Volumetric Mapping of Bound and Pore Water As Well As Collagen Protons in Cortical Bone Using 3D Ultrashort Echo Time Cones MR Imaging Techniques

Cortical bone assessment using magnetic resonance imaging (MRI) has recently received great attention in an effort to avoid the potential harm associated with ionizing radiation-based techniques. Ultrashort echo time MRI (UTE-MRI) techniques can acquire signal from major hydrogen proton pools in cortical bone, including bound and pore water, as well as from the collagen matrix. This study aimed to develop and evaluate the feasibility of a technique for mapping bound water, pore water, and collagen proton densities in human cortical bone ex vivo and in vivo using three-dimensional UTE Cones (3D-UTE-Cones) MRI. Eight human tibial cortical bone specimens (63 ± 19 years old) were scanned using 3D-UTE-Cones sequences on a clinical 3 T MRI scanner and a micro-computed tomography (μCT) scanner. Total, bound, and pore water proton densities (TWPD, BWPD, and PWPD, respectively) were measured using UTE and inversion recovery UTE (IR-UTE) imaging techniques. Macromolecular proton density (MMPD), a collagen representation, was measured using TWPD and macromolecular fraction (MMF) obtained from two-pool UTE magnetization transfer (UTE-MT) modeling. The correlations between proton densities and μCT-based measures were investigated. The 3D-UTE-Cones techniques were further applied on ten young healthy (34 ± 3 years old) and five old (78 ± 6 years old) female volunteers to evaluate the techniques' feasibility for translational clinical applications. In the ex vivo study, PWPD showed the highest correlations with bone porosity and bone mineral density (BMD) (R = 0.79 and - 0.70, p < 0.01). MMPD demonstrated moderate to strong correlations with bone porosity and BMD (R = -0.67 and 0.65, p < 0.01). MMPD showed strong correlation with age in specimens from female donors (R = -0.91, p = 0.03, n = 5). The presented comprehensive 3D-UTE-Cones imaging protocol allows quantitative mapping of protons in major pools of cortical bone ex vivo and in vivo. PWPD and MMPD can serve as potential novel biomarkers to assess bone matrix and microstructure, as well as bone age- or injury-related variations.