Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics

Abstract

In vivo μCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

Intermittent Parathyroid Hormone After Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats

“…A 3D, in vivo dynamic bone histomorphometry technique was developed to track bone resorption and formation activities. (30,32) A trabecular bone subvolume (1.575 Â 1.575 Â 1.05 mm 3 ) of each week in phase 2 (weeks 12 to 16) was subtracted from the registered subvolume of the previous week (weeks 11 to 15) by comparing two subsequent, registered scans. The bone voxels that exist in the second scan but do not exist in the first scan were defined as new bone formation (green; Fig.…”

“…A number of studies suggested a positive effect of combined or tandem bisphosphonate and PTH therapies, attesting to PTH's anabolic effect in the absence of resorption . In our previous studies, we developed a set of in vivo imaging techniques that can assess bone formation and resorption activities simultaneously and longitudinally . By applying these techniques to 3‐month‐old, intact female rats we demonstrated an additive effect by combined PTH and alendronate (ALN, a bisphosphonate) treatments on bone microarchitecture and stiffness over either monotherapy .…”

“…(21)(22)(23)(24)(25)(26)(27)(28) In our previous studies, we developed a set of in vivo imaging techniques that can assess bone formation and resorption activities simultaneously and longitudinally. (29)(30)(31)(32) By applying these techniques to 3-month-old, intact female rats we demonstrated an additive effect by combined PTH and alendronate (ALN, a bisphosphonate) treatments on bone microarchitecture and stiffness over either monotherapy. (29,30) Therefore, we hypothesized that PTH is able to act through both resorption-dependent and resorptionindependent pathways to promote new bone formation after prolonged bisphosphonate treatment.…”

Structural Adaptations in the Rat Tibia Bone Induced by Pregnancy and Lactation Confer Protective Effects Against Future Estrogen Deficiency

“…In vivo μCT images of the proximal tibia made at weeks 0 and 4 post-OVX were used to assess the effects of reproductive history on the post-OVX deterioration of individual trabecular elements. For each rat, sequential μCT images were registered to precisely align the trabecular features, as described in (20,25,26) , and a 1.5×1.5×1 mm trabecular subvolume located 1 mm distal to the growth plate was extracted from μCT images at 0 and 4 weeks post-OVX. The post-OVX changes of each individual trabecula, such as percent bone loss due to trabecular thinning, rod disconnection, or plate perforation, were quantified through an individual trabecular dynamics (ITD) analysis, as described in (27) .…”

A new method to monitor bone geometry changes at different spatial scales in the longitudinal in vivo μCT studies of mice bones

“…The measurement is based on the 3D rigid image registration of the time-lapsed in vivo μ CT scans. The bone formation and resorption are detected according to the appearance and disappearance of the voxels at consecutive scans [5, 13, 14]. The use of in vivo μ CT measurements enables longitudinal studies where each mouse is the control of itself; this can reduce the number of animals required to achieve properly powered conclusion of 60%, if compared to cross-sectional studies [15, 16].…”