The effect of voxel size on high‐resolution peripheral computed tomography measurements of trabecular and cortical bone microstructure

Abstract

Purpose: Accurate quantification of bone microstructure plays a significant role in understanding bone mechanics and response to disease or treatment. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) allows for the quantification of trabecular and cortical structurein vivo, with the capability of generating images at multiple voxel sizes (41, 82, and 123 μm). The aim of this study was to characterize the effect of voxel size on structural measures of trabecular and cortical bone and to determine accuracy in reference to micro‐CT (µCT), the gold standard for bone microstructure quantification. Methods: Seventeen radii from human cadaver specimens were imaged at each HR‐pQCT voxel size and subsequently imaged using µCT. Bone density and microstructural assessment was performed in both the trabecular and cortical compartments, including cortical porosity quantification. Two distinct analysis techniques were applied to the 41 μm HR‐pQCT data: the standard clinical indirect analysis and a direct analysis requiring no density or structural model assumptions. Analysis parameters were adjusted to enable segmentation and structure extraction at each voxel size. Results: For trabecular microstructural measures, the 41 μm HR‐pQCT data displayed the strongest correlations and smallest errors compared to µCT data. The direct analysis technique applied to the 41 μm data yielded an additional improvement in accuracy, especially for measures of trabecular thickness. The 123 μm data performed poorly, with all microstructural measures either having moderate or nonsignificant correlations with µCT data. Trabecular densitometric measures showed strong correlations to µCT data across all voxel sizes. Cortical thickness was strongly correlated with µCT values across all HR‐pQCT voxel sizes. The accuracy of cortical porosity parameters was highly dependent on voxel size; again, the 41 μm data was most strongly correlated. Measures of cortical density and pore diameter at all HR‐pQCT voxel sizes had either weak or nonsignificant correlations. Conclusions: This study demonstrates the effect of voxel size on the accuracy of HR‐pQCT measurements of trabecular and cortical microstructure and presents parameters for HR‐pQCT analysis at nonstandard resolutions. For all parameters measured, correlations were strongest at 41 μm. Weak correlations for porosity measures indicate that a better understanding of pore structure and resolution dependence is needed.

Structural analysis of cortical porosity applied to HR-pQCT data

“…36 Parameters for the connectivity filter that were dependent on voxel size were scaled as necessary for each resolution data set. 35 Due to the disparity in resolution between the HR-pQCT and μCT images, the level of pore structure captured using μCT vastly differed from that captured using HR-pQCT. To account for this difference in resolution, pores with a diameter smaller than 82 μm were removed from the μCT and the 41 μm HR-pQCT images prior to analysis [ Fig.…”

“…The parameters for this process differed for each HR-pQCT voxel size; specific values have been documented in a previous study. 35 The resulting segmented image and the periosteal contour generated previously were then used to create an endosteal contour through a series of dilations and erosions and the application of a connectivity filter. 36 The cortical compartment was identified by subtracting the endosteal contour from the periosteal contour.…”

“…For HR-pQCT images, the cortical mask was applied to the binary image created using a L-H filter and fixed threshold as described in previous publications. 35,36 For μCT images, the binary image was created by applying an automatically selected adaptive-iterative threshold to the original grayscale image.…”

“…[31][32][33][34] The current generation of HR-pQCT scanners provide volumetric data with voxel sizes of 41 and 82 μm (88 and 128 μm spatial resolution, respectively, 10% MTF). 35 At these resolutions larger canals and resorption spaces can be visualized directly. Since the standard HR-pQCT analysis protocol mainly provides morphometric measures of trabecular microstructure (trabecular number, thickness, and separation), a number of analysis techniques have been developed to expand microstructural characterization of both trabecular and cortical compartments.…”

The clinical contribution of cortical porosity to fragility fractures

“…8,11 Studies using high-resolution peripheral quantitative computed tomography (HR-pQCT) to quantify porosity (XtremeCT; Scanco Medical AG, Bruttisellen, Switzerland) present low values of porosity (between 1% and 15%) because of quantifying only porosity of the compactappearing cortex [12][13][14][15][16][17] and only pores over 100 mm, although 60% of cortical pores are under 100 mm in diameter. [18][19][20] This threshold-based image analysis underestimates porosity by including only completely empty voxels and excluding the voxels containing both void and bone matrix. 11 Furthermore, direct measurements of cortical bone water content using deuterium oxide or dehydration experiments report a void volume between 15 and 40%, suggesting an under-reporting of porosity.…”