Elsevier

Medical Engineering & Physics

Volume 35, Issue 11, November 2013, Pages 1645-1650
Medical Engineering & Physics

Micro-CT evaluation of bone defects: Applications to osteolytic bone metastases, bone cysts, and fracture

https://doi.org/10.1016/j.medengphy.2013.05.016Get rights and content

Abstract

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Spmax) by 72.8%. Regression modeling revealed SpSD (β = 0.974, p < 0.0001) to be a significant predictor of the defect volume (R2 = 0.949) and Spmax (β = 0.712, p < 0.0001) and SpSD (β = 0.271, p = 0.022) to be significant predictors of the defect diameter (R2 = 0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone.

Introduction

Defects or flaws in a material reduce its strength by magnifying local stresses [1]. In the case of bone, defects may include bone metastases, cysts, and drill holes for stabilizing or studying fracture repair. These defects can occur in the cortex, the dense material that surrounds bone, or in the interior trabecular bone network. Cellular solids, such as trabecular bone, wood, and engineered foams, are particularly sensitive to structural defects [2]. The loss of structural members has been shown to be more detrimental to strength than an equivalent reduction in apparent density through uniform thinning of its members [2], [3], and failure of trabecular bone samples has been found to localize in regions of low bone volume fraction and connectivity density [4]. The evaluation of defects is, therefore, an important aspect of evaluating a material's strength, in particular in the case of bone where these defects are associated with pain and fragility [5].

Micro-computed tomography (micro-CT) is a non-destructive three-dimensional (3D) imaging modality and the gold standard for evaluating bone microarchitecture; however, its application to bone metastasis research, including evaluation of bone destruction and treatment, has been challenging. Common human cancers, including lung, breast, and prostate, have the potential to spread to bone, and often the skeleton becomes the most heavily burdened site of tumors in the advanced stages of these diseases [5]. Bone metastases can be induced in immune-compromised mice by intra-cardiac injection with tumor cells [6], the more common method, or by direct injection into the bone [7], [8], [9]. Regardless of the method used, when the tumor burden is severe, and in particular when the tumor has interrupted the cortex, it becomes difficult to define the region of interest required to perform a standard micro-CT bone morphological analysis and to evaluate bone quality [8]. Due to the high inter-individual variability in bone properties [10], the intra-cardiac method, which does not allow for control for the site or tumor burden, poses the additional challenge of how one identifies a potential metastasis and quantifies changes that occur with time or treatment. Scoring of X-rays is currently the most common procedure for evaluating osteolytic bone metastases in both clinical practice and animal research, but it is only useful when osteolytic damage is severe. Furthermore, because radiological images are two-dimensional, measurements will be sensitive to the image's orientation, and this imaging modality is limited in its ability to provide a detailed evaluation of bone quality.

Evaluation of bone defects, including osteolytic bone metastases, cysts, and burr-hole fractures, presents challenges when evaluating bone quality by micro-CT. Defects can be highly variable across individuals and it has been unclear which measures of bone quality provide the best indication of the presence of these types of defects. Variability in defect location and severe deterioration of the bone make it difficult to determine an appropriate region of interest for analysis, in particular for cross-sectional studies where there is no internal control available, nor repeat measurements over time, to mitigate some of the variability. Bone mineral density (BMD), as measured by micro-CT, has been shown to have a stronger correlation with bioluminescence imaging, indicative of tumor growth, over radiological scoring [11]; however, direct quantitative metrics are needed. Therefore, the goal of this research is to establish a new methodology based on a micro-CT measure of microarchitectural bone spacing as a sensitive, quantitative tool to quantify and monitor bone defects. These quantitative data will be important for the development of treatments related to burr-hole fracture healing and metastatic tumor burden.

Section snippets

Materials and methods

Micro-CT datasets for illustration of the methodology were selected from two independent mouse studies, both resulting in focal defects, performed in our laboratory between 2005 and 2009. The first study examined fracture healing in mice subjected to a burr-hole defect in the proximal tibia [12]. The second study examined bone metastatic growth in mice subjected to intra-cardiac injection with human breast cancer cells [13]. These studies were carried out in compliance with the Canadian Council

Burr-hole defect

The absolute difference in bone quality parameters between limbs containing the burr-hole defect and the intact limb are presented as box plots (Fig. 3). The presence of the defect increased Sp by 27.6% (p < 0.0001), SpSD by 113% (p < 0.0001), and Spmax by 72.8% (p < 0.0001). It significantly increased BV/TV (p = 0.013), but only by 3%, indicating that is a much less sensitive parameter than Sp, SpSD, and Sp_max. The other morphological parameters were not significantly influenced by the defect,

Discussion

This study demonstrates how standard micro-CT morphological analysis can be adapted to overcome the common problem of evaluating bone defects, which is complicated by the high variability in defect size and location; traditional morphological analysis variables typically mask these important changes. Our results show that both types of defects (burr-hole and osteolytic metastases) greatly influence the distribution of bone spacing (Sp) whereas other parameters showed limited sensitivity to

Conclusions

The technique we propose here is a fast and quantitative approach to measuring bone defects. These can occur in various forms and present challenges to adequately quantify when using a standard micro-CT evaluation. The method using spacing as a quantitative basis for assessing burr-hole defects and bone metastases in a mouse model is an efficient approach with potential for other applications using 3D imaging modalities.

Acknowledgements

The authors would like to thank R.J. Klinck and J. Taiani, for their assistant with micro-CT data collection and for performing the burr-hole surgical procedure.
Conflict of interest

None declared.
Funding

This study was supported by a Translational Group Grant from the Alberta Cancer Foundation. FRJ was the recipient of a Canada Research Chairs award; SKB holds the Rintoul Chair in Bone and Joint Research.
Ethical approval

These studies were carried out in compliance with the Canadian Council of

Cited by (16)

  • Multi-functional osteoclasts in matrix-based tissue engineering bone

    2022, Chinese Journal of Traumatology - English Edition
    Citation Excerpt :

    There are many elements which could lead to bone defects such as trauma, infection and tumour. Traditional bone defect treatment methods have shortcomings, such as long treatment cycle, high cost, uncontrollable curative effect and complications (infection and nonunion), which bring a great burden to patients.2,3 At present, autogenous bone transplantation is the gold standard for the treatment of bone defects, but it has a series of problems, such as limited bone mass in donor areas, postoperative infection and bone defects.4

  • Wavelet transform-based photoacoustic time-frequency spectral analysis for bone assessment

    2021, Photoacoustics
    Citation Excerpt :

    Multi-angle PA-TFSA can also help to locate osteolytic metastasis for guiding treatments. The bone marrow within the trabecular pore space becomes larger as to as to local bone defect in the early stage of osteolytic metastasis [59]. By performing multiple angles scanning on the bone at the absorption peak of bone marrow and analyzing the PA signals with PA-TFSA, the joint time-frequency spectrum at each scanning position can be obtained, as shown in Fig. 2(b).

  • Microimaging

    2019, Principles of Bone Biology
  • Efficient storage of microCT data preserving bone morphometry assessment

    2016, Computers and Electrical Engineering
    Citation Excerpt :

    These data are not necessary for the 3D morphometry computation. The 3D morphometry is computed solely using the bone data [6,7]. Research institutions store sets of microCT data in servers to allow their access and distribution to other institutions via the Internet.

  • Micro-CT of rodents: State-of-the-art and future perspectives

    2014, Physica Medica
    Citation Excerpt :

    Several automatic methods have been developed for the robust selection of the threshold value, mostly based on analysis of a histogram of image intensities [104]. Figure 3 illustrates a bone study using in vivo micro-CT [105]. The study demonstrates that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia for two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases.

View all citing articles on Scopus
View full text