Elsevier

Bone

Volume 63, June 2014, Pages 147-157
Bone

Original Full Length Article
Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

https://doi.org/10.1016/j.bone.2014.03.001Get rights and content

Highlights

  • We evaluated the in vivo reproducibility of the HR-pQCT system using cross-sectional area (CSA)-based registration and 3D registration.

  • CSA registration improved reproducibility of geometry and density parameters compared to without registration.

  • 3D registration further improved reproducibility of cortical geometry and microstructure.

  • The impact of 3D registration on whole bone stiffness was negligible.

Abstract

Definition of identical regions between repeated computed tomography (CT) scans is a key factor to monitor changes in bone microarchitecture. In longitudinal studies, accurate determination of the volume of interest (VOI), using three dimensional (3D) registration may improve precision. Therefore, the aim of our study was to investigate the short-term reproducibility of bone geometry, density, microstructure and biomechanical parameters assessed by HR-pQCT and micro-finite element (μFE) derived analyses, using the cross-sectional area (CSA) registration method in comparison with the use of 3D registration, to find overlapping regions between scans.

Fifteen healthy individuals (aged 21–47 years) underwent 3 separate scans at the distal radius and tibia, within a one-month interval. Reproducibility was assessed after double contouring the cortical compartment and after applying three different methods to determine the common region between repeated scans: (i) the VOI was determined with no registration, i.e., on 110 slices, (ii) the VOI was determined after CSA-based registration, and (iii) the VOI was determined after 3D registration.

Both pre- and post-registration short-term reproducibility for each subject was determined. With no registration, CVrms of geometry parameters ranged from 0.5 to 3.7%, showing a slight variation in the CSA between scans. When the CSA registration method was employed, the variability of geometry (CVrms < 1.8%) and density parameters (CVrms < 1.8%), was better than that obtained without registration. By removing the effect of repositioning, the 3D registration further improved the reproducibility of cortical bone measurements compared to other methods. Indeed, significant improvements were found for cortical geometry and microstructure measurements (CVrms ranged from 0.4% to 10.7% at both sites; p < 0.05), whereas the impact on trabecular bone measurements was restricted to its geometry parameter. The repositioning error was significantly reduced, most markedly at the radius compared to the tibia.

For μFE measures, the impact of 3D registration on whole bone stiffness was negligible, indicating adequate assessment of longitudinal changes in estimated biomechanical properties, even without registration.

In conclusion, we have shown that the 3D registration improved the identification of the common region retained for longitudinal analysis, contributing to improve the reproducibility of cortical bone parameter measurements. We also quantified the minimally detectable bone changes to help designing future studies with HR-pQCT.

Introduction

With the development of high-resolution peripheral quantitative computed tomography (HR-pQCT), a direct quantification of three important determinants of bone quality: microarchitecture, mineralization and biomechanical properties has become possible. This technique enables in vivo measurements at peripheral sites such as the distal radius and tibia, with a nominal isotropic voxel size of 82 μm. Bone microarchitecture parameters measured by HR-pQCT have been found to be associated with prevalent fracture in postmenopausal women and older men independently of areal bone mineral density (aBMD) [1], [2], [3], [4], [5]. Bone strength, estimated using micro-finite element analysis (μFEA), was also associated with prevalent fracture [6], [7], [8], [9], [10], [11], [12], [13], [14]. Moreover, HR-pQCT has been used to assess age-related bone loss [15], [16], [17], [18], [19] and to monitor variations in microarchitecture parameters during osteoporosis treatments [20], [21], [22], [23], [24], [25], [26].

The reproducibility of in vivo measurements is affected by significant sources of error including: poor calibration, movement artifacts, physical positioning, and scanning region selection for maximizing repeated measurements. By providing careful instructions to the subject, it is possible to improve reproducibility via reduction of movement artifacts, however the repositioning remains challenging.

With the standard scanning approach, immobilization of the arm or leg in an anatomically formed carbon fiber shell is used to provide support during the examination, and a reference line relative to anatomical landmarks is used to select the scanning region. Nevertheless, the repositioning of the limb in the exact same way remains a manual process with limited precision, and subsequently differences in scanning region exist between baseline and follow-up scans.

To overcome part of the repositioning error, a cross-sectional area (CSA) registration method was embedded within the HR-pQCT software (Image Processing Language, v5.16, Scanco Medical AG, Brüttisellen, Switzerland). This method was designed to correct axial misplacement between successive scans but did not take into account possible tilt of the limb. Given the dimensions of the scan region, even small tilt angles can lead to a considerable mismatch in the selected region. Only a three dimensional (3D) image registration process could provide an accurate alignment of the repeated scans, and thus may offer an improvement in the reproducibility of bone measurements by decreasing the repositioning error.

Indeed, Macneil et al. have reported an improved reproducibility with 3D registration based on gray-level images, most markedly for total and cortical volumetric BMD but not for trabecular morphological parameters [27]. Shi et al. introduced a 3D registration method based on registered masks after down-sampling gray-level images and demonstrated that bone density and trabecular architecture were comparable with those obtained using the CSA registration method [28].

So far, however, no study has reported the impact of 3D registration on the reproducibility of cortical microstructural parameters, which may be affected by small tilt errors more than the trabecular bone parameters. Also, none of these earlier studies investigated whether 3D registration could improve the reproducibility of the biomechanical parameters. Finally, the different studies conducted so far used different registration software and algorithms. Recently, a 3D registration algorithm has become available as part of the standard HR-pQCT software, which makes this available to all users. To date, no results were reported with regard to the reproducibility of this algorithm and implementation and validation relative to other studies was lacking.

The aim of our study was to apply a fully automated 3D registration process between repeated measurements to determine whether short-term reproducibility of bone microarchitectural and biomechanical parameters could be improved compared to using non-registered images and using the standard CSA-based registration method, at the radius and tibia.

Section snippets

Subjects

In vivo measurements were performed in 15 healthy subjects (aged 21–47 years), with no history of previous fracture, or bone-related ailments (recorded by a questionnaire). All of them were scanned three times within one month at both the non-dominant radius and tibia [29]. The time lag between two measurements varied between the same day, after complete repositioning, and a week. All measurements were performed by a single operator, who had been managing the system for one year.

The protocol was

Image quality

Among the 90 measurements, only one scan (grade 4) was excluded and repeated on the same day. The image quality ranged from grade 1 to grade 3 (grade 1: n = 10 / 25, grade 2: n = 22 / 17, and grade 3: n = 13 / 3, for the radius/tibia respectively).

3D registration accuracy

The 3D registration process was applied on a subset of 10 original and transformed images. The common VOI was thereafter applied to the original image with a mean overlap of 99.8% at the radius and 99.9% at the tibia compared to baseline VOI. Results between

Discussion

We have evaluated the in vivo clinical performance of the HR-pQCT system to longitudinally assess bone changes, by determining short-term reproducibility of geometry, density, microarchitecture and biomechanical measures at the distal radius and tibia, using two different registration methods.

We found that the CSA registration improved reproducibility of the geometry measures and the radius total density, compared with no registration. 3D registration further improved the reproducibility of the

Conflict of interest statement

Dr. van Rietbergen serves as consultant for Scanco Medical AG.

All other authors have no conflicts of interest.

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