Comprehensive Validations of HR-pQCT Based Morphological ... · were registered with the clinical...
Transcript of Comprehensive Validations of HR-pQCT Based Morphological ... · were registered with the clinical...
Comprehensive Validations of HR-pQCT Based Morphological and Biomechanical Measures of
Human Distal Radius and Tibia
Bin Zhou1, Ji Wang, M.S1, Y. Eric Yu1, Zhendong Zhang1, Ruoyu Sheng1, Alexander Wang1, Kyle Nishiyama,
PhD2, Elizabeth Shane2, X. Edward Guo1. 1Columbia University, New York, NY, USA, 2Columbia University Medical Center, New York, NY, USA.
Disclosures: B. Zhou: None. J. Wang: None. Y. Yu: None. Z. Zhang: None. R. Sheng: None. A. Wang:
None. K. Nishiyama: None. E. Shane: None. X. Guo: None.
Introduction: High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in vivo
imaging modality to assess the three-dimensional (3D) microstructure of cortical and trabecular bone at
distal radius and tibia. HR-pQCT has demonstrated its capability in detecting diseases and treatment-
related bone microstructural changes, as well as providing additional fracture risk determinants
compared to dual energy x-ray absorptiometry (DXA) [1-2]. Typically, a standard 9.02 mm segment of
the distal radius or tibia is imaged and processed for microstructural and biomechanical analyses. In
addition, advanced individual trabecula segmentation (ITS), which decomposes trabecular bone
microstructure into individual trabecular plates and rods, has been also used on the HR-pQCT images to
provide additional trabecular morphological assessments in clinical studies. However, all these
techniques, originated from high-resolution micro CT (µCT), have not been rigorously and
comprehensively validated in human radii and tibiae. For example, the clinical standard morphological
and advanced ITS morphological analyses have not been validated for HR-pQCT of both tibia and radius
segments. The biomechanical analyses of these standardized HR-pQCT segments have not been
compared with the gold standard experimental biomechanical measurements. Furthermore, it remains
to be determined whether the current selection of the HR-pQCT segment is representative of the entire
radius and tibia, both morphologically and biomechanically. Therefore, in this study we 1) performed
HR-pQCT standard, ITS morphological and biomechanical analyses and compare the HR-pQCT measures
to those by gold standard µCT and directly mechanical testing on both radii and tibiae from the same
cadaveric human subjects; 2) applied HR-pQCT analyses on three adjacent regions along distal radius
and tibia to examine the variations of bone geometry and morphology in different regions (Fig. 1), and
determined their associations with the experimentally determined whole bone stiffness.
Methods: 26 paired whole tibiae and radii bone were first scanned by HR-pQCT at 82 µm and µCT at 37
µm. The radius and tibia segment corresponding to the clinical HR-pQCT region was prepared and
scanned again by HR-pQCT. Standard HR-pQCT evaluation was applied on the segment for
microstructural evaluation. Based on the threshold image of HR-pQCT segments, standard µCT
evaluations (direct) were applied to calculate model-independent trabecular microstructural
parameters. The µCT image was registered to the HR-pQCT segment and standard µCT evaluation was
performed on the µCT trabecular compartment. ITS analyses were then applied to examine the
trabecular plate and rod related microstructural parameters. The whole radius and tibia HR-pQCT image
were registered with the clinical segment image and two adjacent regions were determined and applied
to HR-pQCT evaluations: 1) the most distal region, the section between the distal radial or tibial end
surface and the start of the standard region; 2) the proximal region, the section starting from the end of
standard region and contain a 24.6 mm section toward proximal direction. Before the segment was cut,
the entire radius and tibia were embedded with PMMA and nondestructively tested mechanically to
measure the whole bone stiffness. After the segment was cut, uniaxial mechanical testing was
performed to measure the segment stiffness. Finite element analyses were performed based on the
clinical segment HR-QCT images and the accuracy was examined through comparison with µCT image
based FEA predications and mechanical testing results. Spearman correlation coefficient was used to
characterize the correlations between the HR-pQCT measurements and whole bone stiffness. Paired
Student’s t-tests were applied to examine the difference between HR-pQCT and µCT measurements.
Results: All of the standard HR-pQCT microstructural measurements were significantly different from
those of µCT at both radius and tibia (Table 1). The HR-pQCT standard evaluation parameters (BV/TVd,
Tb.N*, Tb.Th and Tb.Sp) and direct measurement parameters (BV/TV, Tb.N*, Tb.Th* and Tb.Sp*)
correlate significantly and most of them strongly with the corresponding gold-standard µCT
measurements (r=0.56~0.96) at the radius and tibia. Significant correlations were also found for BS/BV,
Conn.D and SMI between direct and µCT measurements (r=0.72~0.92), at the radius and tibia. ITS
measures based on HR-pQCT images were significantly different from those based on registered gold-
standard µCT images. HR-pQCT measures of pBV/TV, aBV/TV, pBV/BV, rBV/TV, pTb.N, pTb.Th and rTb.Th
were found strongly to moderately correlated with those of µCT measures at the radius and tibia
(r=0.65~0.92). However, there were no correlations for rTb.N, R-R Junc.D and P-R Junc.D at the radius
and rTb.ℓ, P-R Junc.D and R-R Junc.D at the tibia between HR-pQCT and µCT image. The HR-pQCT based
FEA predications were found to be excellently correlated with those of the µCT predications and
mechanical testing results (r=0.96~0.98) at radius and tibia. HR-pQCT measurements of the standard
region only moderately correlated with whole bone stiffness at both radius and tibia (Table 2). The
correlations between the HR-pQCT measurements and whole bone stiffness were found to be the
highest at the distal section for both radius and tibia. Among the HR-pQCT parameters at distal section,
average BMD and trabecular BMD were most highly correlated with whole bone stiffness at the tibia
(r=0.93). Similarly, trabecular BMD had the highest correlation with whole bone stiffness at the radius
(r=0.9).
Discussion: The accuracy of HR-pQCT and HR-pQCT based ITS morphological analysis of the standard
clinical interest region was fully examined by comparing with gold-standard high resolution µCT and
direct mechanical testing measures at both the radius and tibia. Although differed, the HR-pQCT and HR-
pQCT based ITS morphological measurements were strongly correlated with those of µCT
measurements. pBV/TV and aBV/TV, two parameters that significantly contribute to bone strength,
correlate the highest with gold-standard µCT measures. The applications of these two parameters would
provide important additional insights in current clinical HR-pQCT studies. The moderate correlations
between the HR-pQCT measurements from standard clinical region and whole bone stiffness suggested
that the morphological parameters of the HR-pQCT scan region were not representative of the whole
bone mechanical properties. The significantly higher correlations between the HR-pQCT measures and
whole bone stiffness at the most distal section indicated that the clinical HR-pQCT scanning region
should consider moving toward distal direction to better represent the whole bone mechanics.
Significance: HR-pQCT and HR-pQCT based ITS morphological evaluation has the potential to be the
clinical standard for microstructural evaluations. The standard HR-pQCT scans should include more from
distal end to better represent whole bone quality.
ORS 2015 Annual Meeting
Poster No: 1504