Assessment of trabecular bone quality of the proximal femur in vivo: A Preliminary Study
Maria Kalimeri1, Christiani Jeyakumar Henry2, Xiao Di Su3, Marlena C. Kruger4, and John J. Totman1

1A*STAR-NUS Clinical Imaging Research Centre, Singapore, Singapore, 2Clinical Nutrition Research Centre, Singapore, Singapore, 3Institute of Materials Research and Engineering, Singapore, Singapore, 4School of Food and Nutrition, College of Health, Massey University, Palmerston North, New Zealand

Synopsis

Osteoporosis is a skeletal disorder that affects predominantly postmenopausal women. The screening method for osteoporosis is Dual X-ray Absorptiometry (DXA), which has several limitations, including the inability to differentiate between trabecular and cortical bone. 3D imaging modalities can give information about each bone component, which contribute to bone strength in different ways. MRI is an attractive alternative due to lack of ionising radiation. In this abstract, we present a method for bone density assessment of trabecular bone in the proximal femur using MRI. Strong correlations with both DXA and Quantitative Computed Tomography (QCT) measurements of similar regions were observed.

Purpose

Osteoporosis is a skeletal disorder that predominantly affects postmenopausal women. It is characterised by declining bone strength and can lead to bone fractures. Osteoporosis screening is routinely performed with Dual X-ray Absorptiometry (DXA), which measures areal Bone Mineral Density (BMD). DXA is a standardised technique and is widely used with high precision, but it has several limitations in monitoring interventions and predicting fractures. DXA could overestimate BMD in heavier subjects or those with diabetes, aortic calcifications or degenerative disease, among others1. In addition, BMD only partly explains bone strength; the properties of bone that are not assessed with BMD are defined as bone quality2,3. The different components of the bone (cortical shell that encapsulates trabecular bone) contribute to bone strength in different ways4, 5 and DXA, as a projection method, fails to take this into account. 3D imaging methods, such as Quantitative CT (QCT) and MRI, can be used to assess bone strength and the lack of ionizing radiation makes MRI attractive for serial measurements. As the spine and the proximal femur are more challenging sites to image with MRI (presence of hematopoietic marrow, lack of dedicated coils), research on bone MRI has focused mostly on peripheral sites (tibia, heel, and radius)6. The femoral neck, however, is a common site for osteoporotic fractures, so accurate assessment of bone quality in this site is important in clinical practice. In this abstract, we present a method for assessing trabecular bone density, which has been shown to predict the risk of fracture4, in vivo on the proximal femur using MRI.

Methods

Of the 100 post-menopausal Chinese-Singaporean women that will be recruited in this study, data from 9 have been analysed to date (average age 59.6±5 years). All subjects underwent MRI (3T Siemens Prisma), QCT (Siemens mCT) scans of the proximal femur and whole body DXA (Hologic Discovery QDR 4500). A proton density (PD, TR=929ms, TE=54ms, 32 averages, acq time ~19min) sequence was used to acquire 6 coronal slices of the proximal femur of the non-dominant leg (voxel size 0.26x0.26x1.5mm), using an 18-channel body array coil (Siemens). Both hips were scanned with QCT, using a commercial phantom (Mindways QCT Pro). Images of a PD dataset and a QCT image slice are shown in Fig.1 and Fig. 2, respectively. Bias field correction was performed on the PD images7 and DXA equivalent volumes of interest (VOIs), femoral neck and the total proximal femur, were drawn manually on the PD images. Due to limitations in the resolution (trabecular size is 100-150um), PD voxels cannot contain pure trabecular bone, so calculating bone content per voxel (bone volume fraction - BVF) was a more realistic approach than classifying voxels as bone or marrow. BVF was calculated using the method proposed by Vasilic and Wehrli8. BVF maps of the total femur and femoral neck of the dataset in Fig. 1 are shown in Fig. 3 and Fig. 4, respectively. The PD VOIs were registered to the QCT images, and volumetric BMD (vBMD) was calculated for each VOI. Analysis was performed using in-house developed software (MATLAB R2013b, ITK) and dedicated software (Fiji9, ITK-Snap, elastix10, 11).

Results

DXA measurements gave an average BMD of 0.61±0.12g/cm2 for the femoral neck and 0.76±0.11 g/cm2 for total femur of the non-dominant leg of the subjects. For each subject, the average BVF per region (MRI) was compared to the average vBMD (QCT) of the same VOI and the respective areal BMD (DXA). Average BVF can be considered a surrogate measure for trabecular density. Linear regression analysis showed strong correlations between PD and DXA BMD as well as PD and QCT vBMD measurements, see Table 1. The stronger correlation of average BVF to average QCT vBMD was expected, since the QCT measurements were performed on the same VOI as the MRI measurements, while a bigger volume, which also contained cortical bone, contributed to the DXA BMD measurements.

Discussion

In this abstract, we presented a method to assess the trabecular bone density of a trabecular VOI in the proximal femur using MRI. The strong correlations of trabecular BVF with DXA BMD and QCT vBMD measurements show that it could be used to assess bone quality, instead of DXA or QCT.

Conclusion

Extensive evaluation is needed to prove that BVF could be a useful biomarker in clinical practice. Such a biomarker may predict fracture risk and be sensitive to bone quality changes at different time points, due to a nutritional or drug intervention.

Acknowledgements

This project is part funded by Singapore-New Zealand Foods for Health Grant (BMRC grant 14/1/16/24/008).

References

1 T. Link, Osteoporosis imaging: state of the art and advanced imaging , Radiology. 263(1):3-17, April 2012

2 Griffith JF et al, Looking beyond bone mineral density: Imaging assessment of bone quality, Ann N Y Acad Sci. 2010;1192:45-56

3 NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy, Osteoporosis prevention, diagnosis, and therapy JAMA. 2001;285:785-95

4 Felix W. Wehrli et al, Quantitative MRI for the assessment of bone structure and function , NMR Biomed. 2006; 19(7): 731-764

5 Won C Bae et al, Quantitative Ultrashort Echo Time (UTE) MRI of Human Cortical Bone: Correlation With Porosity and Biomechanical Properties, Journal of Bone and Mineral Research, 27(4): 848-857 April 2012

6 Krug et al. Feasibility of in vivo structural analysis of high-resolution magnetic resonance images of the proximal femur, Osteoporos Int, 16(11), 1307-1314, Nov 2005

7 N. J. Tustison et al, N4ITK: Improved N3 Bias Correction, IEEE Trans Med Imaging, 29(6): 1310–1320, June 2010

8 B. Vasilic and F.W.Wehrli, A Novel Local Thresholding Algorithm for Trabecular Bone Volume Fraction Mapping in the Limited Spatial Resolution Regime of In Vivo MRI, IEEE Trans Med Imaging, 24(12): 1574-1585, Dec 2005

9 http://imagej.nih.gov/ij/

10 S. Klein et al, elastix: a toolbox for intensity based medical image registration, IEEE Trans Med Imaging, 29(1): 196 - 205, Jan 2010

11 D.P. Shamonin et al, Fast Parallel Image Registration on CPU and GPU for Diagnostic Classification of Alzheimer’s Disease, Frontiers in Neuroinformatics, 7(50): 1-15, Jan 2014

Figures

Fig. 1: PD dataset, 6 coronal slices, left leg

Fig. 2: QCT, axial slice of both femurs, QCT phantom can be seen under the subject

Fig. 3: BVF map of total femur VOI of dataset in Fig. 1

Fig. 4: BVF map of femoral neck VOI of dataset in Figure 1

Table 1: Correlation coefficients (R) of BVF calculated from PD with DXA BMD and QCT vBMD



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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