Po-hung Wu1, Jing Liu1, Julio Carballido-Gamio2, Misung Han1, Roland Krug1, and Galateia Kazakia1
1Radiology and Biomedical Imaging, University of California - San Francisco, San francisco, CA, United States, 2School of Medicine, Radiology, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States
Synopsis
Pathological cortical bone porosity negatively impacts bone
strength, but the mechanisms of pathological
pore growth are not understood. We hypothesize that the contents of cortical
bone pores (marrow or vessels) may be useful indicators of pore expansion
mechanisms. In this study, we developed a technique using high resolution CT
and DCE-MRI to visualize and identify pore contents. Dynamic features such as
temporal intensity difference and transition slope within pore voxels were
evaluated and clustered by a K-means clustering algorithm. The average
intensity of segmented vessel-filled pores increased over time, demonstrating the
ability of our technique to positively identify vessel-filled pores.
Introduction
Cortical bone porosity is a major determinant of
bone strength1. Metrics of cortical bone porosity can be quantified
from high resolution peripheral quantitative computed tomography (HR-pQCT), and
are widely used in musculoskeletal research. Such indicators of porosity,
however, are unable to explain the mechanisms of pore growth and therefore fail
to predict the development of pathological porosity. To understand the
mechanisms of pore growth, more detailed data are needed. Pore space content
may be a useful indicator of the mechanisms of pore expansion. Specifically,
vessels within newly expanded pores may indicate pore growth driven by the
expansion of the vascular system. Fat cells or marrow within pores may indicate
pore growth driven by marrow compartment expansion. Dynamic contrast-enhanced MRI
(DCE-MRI) is used widely for evaluating tissue perfusion. In this study,
DCE-MRI has been applied for visualization and identification of the contents
of cortical bone pores (marrow or vessels). This novel imaging application is
challenging due to the need for high spatial and contrast resolution.Methods
UCSF
IRB approval was obtained for this study. Distal tibias of 4 volunteers were
imaged using HR-pQCT (XtremeCT Scanco Medical AG) with 60 kVp, 900 μA and
isotropic voxel size 82 μm for cortical bone segmentation and pore mask
definition3. Gadolinium DCE-MRI (3T Signa GE Medical) with
T1-weighted FSE (Slice thickness: 2 mm; TR/TE:500/11.0 ms; Bandwidth: 244.1
Hz/pixel; Flip Angle:; Matrix size: 512x512; FOV=12cm) and SPGR (Slice
thickness: 1 mm; TR/TE:11.8/3.6 ms; Bandwidth: 162.8 Hz/pixel; Flip Angle:; Matrix size: 512x512; FOV=12 cm) sequences were
performed for vessel visualization. DCE-MRI
was applied for 8 minutes with 1 minute injection delay (Gd-DTPA, 0.2mmol/kg). The
DCE-MRI and HR-pQCT scans were co-registered using maximal normalized mutual
information2 (FMRIB Software Library). To eliminate any influence of
mis-registration, the pore masks were dilated before transforming to DCE-MRI
coordinates to assure full coverage of pores. The intensity difference between
each post-enhanced and pre-enhanced MRI volume was calculated for all pixels
inside the dilated, transformed pore mask, and K-means clustering was performed
to detect the candidates of vessel-filled pores4,5. The area under the
post-pre intensity difference curve (AUC), the transition slope (defined as the
change rate of post-pre intensity difference within the “transition period”, defined
as the signal change from 20% to 80% of maximum) and the transition time (the
time interval of the transition period) of candidate pixels were calculated and
evaluated, and a second iteration of K-means clustering was applied to refine
the results of vessel-filled pore identification6 (Fig.1).Results
Our results
demonstrate that DCE-MRI enables the visualization of vessels within cortical
bone pores (Fig. 2), and K-means vessel clustering enables classification of
voxels representing vessels within the 3D data set (Fig.3). The average
intensity of segmented vessel-filled pores increased over time, while the intensity
of non-vessel-filled pores (marrow-filled pores) remained constant after
contrast injection. These results indicate that – within the spatial resolution
limits of our MRI sequences – vessel-filled pores can be discriminated from
marrow-filled pores by the proposed method.Discussion and Conclusion
We have demonstrated the ability of the proposed
technique to positively identify vessel-filled pores and classify pore content
within cortical bone by DCE-MRI and image processing A limitation of this
technique is that many smaller cortical pores and vessels are below the
resolution limits of our imaging techniques; however, we have demonstrated that
large intracortical pores and their contents can be studied using this proposed
technique. By applying these techniques to a longitudinal study, we can
investigate the relationships between pore growth and the expansion of the
vascular system and/or the marrow compartment. Once these relationships are
understood, we can identify biomarkers to predict the progression of porosity
and evaluate therapies to prevent pathological pore progression.Acknowledgements
Funding support was
provided by National Institutes of Health (NIH-NIAMS) Grant NOs. R01AR069670 and R03AR064004References
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