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One possibility for the disproportionate increase in fracture risk with aging relative to the decrease in bone mass is an accumulation of changes to the bone matrix which deleteriously affect fracture resistance. In order to effectively develop new targets for osteoporosis, a preclinical model of the age-related loss in fracture resistance needs to be established beyond known age-related decreases in bone mineral density and bone volume fraction. To that end, we examined long bones of male and female BALB/c mice at 6-mo. and 20-mo. of age and assessed whether material and matrix properties of cortical bone significantly differed between the age groups. The second moment of area of the diaphysis (minimum and maximum principals for femur and radius, respectively) as measured by ex vivo micro-computed tomography (μCT) was higher at 20-mo. than at 6-mo. for both males and females, but ultimate moment as measured by three-point bending tests did not decrease with age. Cortical thickness was lower with age for males, but higher for old females. Partially accounting for differences in structure, material estimates of yield, ultimate stress, and toughness (left femur) were 12.6%, 11.1%, and 40.9% lower, respectively, with age for both sexes. The ability of the cortical bone to resist crack growth (right femur) was also 18.1% less for the old than for the young adult mice. These decreases in material properties were not due to changes in intracortical porosity as pore number decreased with age. Rather, age-related alterations in the matrix were observed for both sexes: enzymatic and non-enzymatic crosslinks by high performance liquid chromatography increased (femur), volume fraction of bound water by 1 H-nuclear magnetic resonance relaxometry decreased (femur), cortical tissue mineral density by μCT increased (femur and radius), and an Amide I sub-peak ratio I 1670 /I 1640 by Raman spectroscopy increased (tibia). Overall, there are multiple matrix changes to potentially target that could prevent the age-related decrease in fracture resistance observed in BALB/c mouse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ultrasound imaging for kidney stones suffers from poorer sensitivity, diminished specificity, and overestimation of stone size compared to computed tomography (CT). The purpose of this study was to demonstrate in vitro feasibility of novel ultrasound imaging methods comparing traditional B-mode to advanced beamforming techniques including plane wave synthetic focusing (PWSF), short-lag spatial coherence (SLSC) imaging, mid-lag spatial coherence (MLSC) imaging with incoherent compounding, and aperture domain model image reconstruction (ADMIRE). The ultrasound techniques were evaluated using a research-based ultrasound system applied to an in vitro kidney stone model at 4 and 8 cm depths. Stone diameter sizing and stone contrast were compared among the different techniques. Analysis of variance was used to analyze the differences among group means, with p < 0.05 considered significant, and a Student's t test was used to compare each method with B-mode, with p < 0.0025 considered significant. All stones were detectable with each method. MLSC performed best with stone sizing and stone contrast compared to B-mode. On average, B-mode sizing error ± SD was > 1 mm (1.2 ± 1.1 mm), while those for PWSF, ADMIRE, and MLSC were < 1 mm (- 0.3 ± 2.9 mm, 0.6 ± 0.8, 0.8 ± 0.8, respectively). Subjectively, MLSC appeared to suppress the entire background thus highlighting only the stone. The ADMIRE and SLSC techniques appeared to highlight the stone shadow relative to the background. The detection and sizing of stones in vitro are feasible with advanced beamforming methods with ultrasound. Future work will include imaging stones at greater depths and evaluating the performance of these methods in human stone formers.

Purpose: Ultrasound methods for kidney stone imaging suffer from poor sensitivity and size overestimation. The study objective was to demonstrate feasibility of non-linear ultrasound beamforming methods for stone imaging, including plane wave synthetic focusing (PWSF), short-lag spatial coherence (SLSC) imaging, mid-lag spatial coherence (MLSC) imaging with incoherent compounding, and aperture domain model image reconstruction (ADMIRE)., Materials and Methods: The ultrasound techniques were evaluated in an in vitro kidney stone model and in a pilot study of 5 human stone formers (n = 6 stones). Stone contrast, contrast-to-noise ratio (CNR), sizing, posterior shadow contrast, and shadow width sizing were compared among the different techniques and to B-mode. CT imaging within 60 days was considered the gold standard stone size. Paired t-tests using Bonferroni correction were performed to evaluate comparing each technique with B-mode., Results: Mean CT measured stone size was 6.0mm (range 2.9-12.2mm) with mean skin-to-stone distance 10.2cm (range 5.4-16.3cm). Compared to B-mode, stone contrast was best with ADMIRE (mean +12.2dB), while SLSC and MLSC showed statistically improved CNR. Sizing was best with ADMIRE (mean +1.3mm error), however this was not significantly improved over B-mode (+2.4mm). PWSF performed similarly to B-mode for stone contrast, CNR, SNR, and stone sizing. In the in vitro model, the shadow contrast was highest with ADMIRE (mean 10.5 dB vs 3.1 dB with B-mode). Shadow sizing was best with SLSC (mean error +0.9mm ± 2.9), however the difference compared to B-mode was not significant., Conclusions: The detection and sizing of stones are feasible with advanced beamforming methods with ultrasound. ADMIRE, SLSC, and MLSC hold promise for improving stone detection, shadow contrast, and sizing., Competing Interests: The authors have declared that no competing interests exist.