Toward the use of MRI measurements of bound and pore water in fracture risk assessment.

The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (Cbw) are lower and concentrations of pore water (Cpw) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of Cbw and Cpw were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores). In Study 1, Cbw was significantly lower (p = 0.0018) and Cpw was higher (p = 0.0022) in the Fx than in the Non-Fx group. In forward stepwise, logistic regression models using Bayesian Information Criterion for selecting the best set of predictors (from imaging parameters, age, BMI, and DXA scanner type), the area-under-the-receiver operator characteristics-curve (AUC with 95 % confidence intervals) was 0.73 (0.56, 0.86) for hip aBMD (best predictors without MRI) and 0.86 (0.70, 0.95) for the combination of Cbw and Cpw (best predictors overall). In Study 2, Cbw was significantly lower (p = 0.0005) in women with OP (23.8 ± 4.3 1H mol/L) than in women without OP (29.9 ± 6.4 1H mol/L); Cpw was significantly higher by estimate of 2.9 1H mol/L (p = 0.0298) with clinical OP, but only when accounting for the type of UTE-MRI scan with 3D providing higher values than 2D (p < 0.0001). Lastly, Cbw, but not Cpw, was sensitive to bone forming osteoporosis medications over 12-months. UTE-MRI-derived measurements of bound and pore water concentrations are potential, aBMD-independent predictors of fracture risk.

Fast bound and pore water mapping of cortical bone with arbitrary slice oriented two-dimensional ultra-short echo time.

PURPOSE: Extend fast, two-dimensional (2D) methods of bound and pore water mapping in bone to arbitrary slice orientation. METHODS: To correct for slice profile artifacts caused by gradient errors of half pulse 2D ultra-short echo time (UTE), we developed a library of predistorted gradient waveforms that can be used to interpolate optimized gradient waveforms for 2D UTE slice selection. We also developed a method to estimate and correct for a bulk phase difference between the two half pulse excitations used for 2D UTE signal excitation. Bound water images were acquired in three healthy subjects with adiabatic inversion recovery prepared 2D UTE, while pore water images were acquired after short-T2 signals were suppressed with double adiabatic inversion recovery preparation. The repeatability of bound and pore water imaging with 2D UTE was tested by repeating acquisitions after repositioning. RESULTS: The library-based interpolation of optimized slice select gradient waveforms combined with the method to estimate bulk phase between two excitations provided compact slice profiles for half pulse excited 2D UTE. Quantitative bound and pore water values were highly repeatable-the pooled SD of bound water across all three subjects was 0.38 mol 1 $$ {}^1 $$ H/L, while pooled SD of pore water was 0.30 mol 1 $$ {}^1 $$ H/L. CONCLUSION: Fast, quantitative, 2D UTE-based bound and pore water images can be acquired at arbitrary oblique orientations after correcting for errors in the slice select gradient waveform and bulk phase shift between the two half acquisitions.

T1 relaxation of bound and pore water in cortical bone.

MRI measures of bound and/or pore water concentration in cortical bone offer potential diagnostics of bone fracture risk. The transverse relaxation characteristics of both bound and pore water are relatively well understood and have been used to design clinical MRI pulse sequences to image each water pool quantitatively. However, these methods are also sensitive to longitudinal relaxation characteristics, which have been less well studied. Here, spectroscopic relaxometry measurements of 31 human cortical bone specimens provided a more detailed picture of T 1 of both bound and pore water. The results included mean, standard deviation, and range of T 1 spectra from both bound and pore water, as well as novel presentations of the 2D T 1 - T 2 distribution of pore water. Importantly, for each sample the pore water T 1 spectrum was found to span more than one order of magnitude and varied substantially across the 31 sample studies. Because many existing methods assume pore water T 1 to be mono-exponential and constant across individuals, the results were used to compute the potential effect neglecting this intra- and intersample T 1 variation on accurate MRI measurement of both bound and pore water concentrations. The greatest effect was found for adiabatic inversion recovery (AIR) based measurements of bound water concentration, which showed an average of 8.8% and as much as 37% error when using a common mono-exponential assumption of pore water T 1 . Despite these errors, the simulated AIR measurements were still moderately well correlated with the bound water concentrations derived from the spectroscopic data.

Finite element analysis of bone mechanical properties using MRI-derived bound and pore water concentration maps.

Ultrashort echo time (UTE) MRI techniques can be used to image the concentration of water in bones. Particularly, quantitative MRI imaging of collagen-bound water concentration (Cbw) and pore water concentration (Cpw) in cortical bone have been shown as potential biomarkers for bone fracture risk. To investigate the effect of Cbw and Cpw on the evaluation of bone mechanical properties, MRI-based finite element models of cadaver radii were generated with tissue material properties derived from 3 D maps of Cbw and Cpw measurements. Three-point bending tests were simulated by means of the finite element method to predict bending properties of the bone and the results were compared with those from direct mechanical testing. The study results demonstrate that these MRI-derived measures of Cbw and Cpw improve the prediction of bone mechanical properties in cadaver radii and have the potential to be useful in assessing patient-specific bone fragility risk.

HR-pQCT parameters of the distal radius correlate with the bending strength of the radial diaphysis.

High resolution, peripheral quantitative computed tomography (HR-pQCT) scanners can now characterize an individual's trabecular architecture, cortical structure, and volumetric bone mineral density at a nominal resolution of 61 µm. While predictions of failure load of the distal radius and tibial diaphysis in compression by finite element analysis (FEA) of HR-pQCT scans have been validated against mechanical tests of cadaveric bones in compression, namely for images with nominal resolutions of 82 µm and 165 µm, the HR-pQCT parameters that best predict bending strength of cortical bone remain unknown. Therefore, we scanned cadaveric forearms from 31 elderly donors (Female: 72.8 ± 8.8 years and Male: 72.1 ± 6.3 years), and then loaded the radial diaphysis to failure in three-point bending after denuding each bone (38 in total). The cortical parameters had stronger correlations with ultimate moment than the trabecular parameters such that cortical area and estimated failure load of the distal radius had the highest Spearman correlation coefficients (r = 0.89 and r = 0.81, respectively, p < 0.0001). Despite being a known determinant of bone strength, cortical porosity of the distal radius did not correlate with ultimate moment (p = 0.8537). In multivariate linear regressions with section modulus (SM) of the radial diaphysis as one of two predictors of bending strength, cortical area and cortical thickness were each significant contributors to the prediction of ultimate moment. Their contribution was one-half and one-third, respectively, of the contribution from SM. None of the HR-pQCT parameters were strongly correlated with post-yield displacement, an indicator of bone brittleness. In support of HR-pQCT imaging of the distal radius to identify individuals with osteoporosis, the present study found that parameters of the cortex and failure load predictions by linear FEA are strongly related to the bending strength of cortical bone.

On the Challenges Associated with Obtaining Reproducible Measurements Using SWEI in the Median Nerve.

This work discusses challenges we have encountered in acquiring reproducible measurements of shear wave speed (SWS) in the median nerve and suggests methods for improving reproducibility. First, procedural acquisition challenges are described, including nerve echogenicity, transducer pressure and transmit focal depth. Second, we present an iterative, radon sum-based algorithm that was developed specifically for measuring the SWS in median nerves. SWSs were measured using single track location shear wave elasticity imaging (SWEI) in the median nerves of six healthy volunteers and six patients diagnosed with carpal tunnel syndrome. Unsuccessful measurements were associated with several challenges including reverberation artifacts, low signal-to-noise ratio and temporal window limitations for tracking the velocity wave. To address these challenges, an iterative convergence algorithm was implemented to identify an appropriate temporal processing window that removed the reverberation artifacts while preserving shear wave signals. Algorithmically, it was important to consider the lateral regression kernel size and position and the temporal window. Procedurally, both nerve echogenicity and transducer compression were determined to impact the measured SWS. Shear waves were successfully measured in the median nerve proximal to the carpal tunnel, but SWEI measurements were significantly compromised within the carpal tunnel itself. The velocity-based SWSs were statistically significantly higher than the displacement SWSs (p < 0.0001), demonstrating for the first time dispersion in the median nerve in vivo using SWEI.