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

Abstract

Longitudinal studies of bone adaptation in mice using in vivo micro-computed tomography ( μ CT) have been commonly used for pre-clinical evaluation of physical and pharmacological interventions. The main advantage of this approach is to use each mouse as its own control, reducing considerably the sample size required by statistical power analysis. To date, multi-scale estimation of bone adaptations become essential since the bone activity that takes place at different scales may be associated with different bone mechanisms. Measures of bone adaptations at different time scales have been attempted in a previous study. This paper extends quantification of bone activity at different spatial scales with a proposition of a novel framework. The method involves applying level-set method (LSM) to track the geometric changes from the longitudinal in vivo μ CT scans of mice tibia. Bone low- and high-spatial frequency patterns are then estimated using multi-resolution analysis. The accuracy of the framework is quantified by applying it to two times separated scanned images with synthetically manipulated global and/or local activity. The Root Mean Square Deviation (RMSD) was approximately 1.5 voxels or 0.7 voxels for the global low-spatial frequency or local high-spatial frequency changes, respectively. The framework is further applied to the study of bone changes in longitudinal datasets of wild-type mice tibiae over time and space. The results demonstrate the ability for the spatio-temporal quantification and visualisation of bone activity at different spatial scales in longitudinal studies thus providing further insight into bone adaptation mechanisms.

Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude

“…This technique provided promising results for the majority of the tibial cross-sections analysed; however, it is inadequate for bony protrusions such as the tibial ridge. Furthermore, while new tissue forms normal to the bone surface (Graham et al, 2012;Pereira et al, 2015;Zhang et al, 2019), the use of a minimum distance technique does not accurately capture Ct.Th when the direction of adaptation (i.e., normal to the surface) is highly offset from the radial direction. Similarly, radial coordinates create issues when determining periosteal and endosteal edges, where in some cases up to four cortical intersection points can be identified for a given radial direction (Bab et al, 2007).…”

Establishment of a guided, in vivo, multi-channel, abdominal, tissue imaging approach

“…This longitudinal study design enables a reduction in animal experiments, as not as many animals have to be sacrificed than for endpoint based analysis methods as, for instance, for histologic analyses. Imaging methods applied in animal research include micro-computed tomography 1 , magnetic resonance imaging 2 , positron emission tomography 3 , ultrasound 4 , and optical imaging. Optical imaging has two significant advantages: Firstly, in combination with fluorescence, variety of different fluorophores such as dyes, antibodies, or fusion proteins are available 5,6 .…”