Accuracy of volumetric bone mineral density measurement in high-resolution peripheral quantitative computed tomography

Abstract

Accurate bone mineral density (BMD) quantification is critical in clinical assessment of fracture risk and in the research of age-, disease-, and treatment-related musculoskeletal changes. The development of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging has made possible in vivo assessment of compartmental volumetric BMD (vBMD) and bone micro-architecture in the distal radius and tibia. HR-pQCT imaging relies on a polychromatic X-ray source and therefore is subject to beam hardening as well as scatter artifacts. In light of these limitations, we hypothesize that the accuracy of HR-pQCT vBMD measurement in the trabecular compartment (vBMD(trab)) is not independent of bone density and geometry, but rather influenced by variations in trabecular bone volume fraction and cortical thickness. The goal of this study, therefore, was to evaluate the accuracy of HR-pQCT vBMD(trab) measurement in the radius and tibia, and to determine the dependence of this measurement on geometric and densitometric parameters. Our approach was to use a series of idealized hydroxyapatite (HA) phantoms with varying densities and geometries to quantify the accuracy of HR-pQCT analysis. Two sets of custom-made HA phantoms designed to mimic the distal tibia and distal radius were manufactured. Geometric and densitometric specifications were based on a dataset of healthy volunteers and osteopenic patients. Multiple beam hardening correction (BHC) algorithms were implemented and evaluated in their ability to reduce measurement error. Substantial errors in measured vBMD(trab) were found. Overestimation of vBMD(trab) increased proportional to cortical shell thickness and decreased proportional to insert density. The most pronounced vBMD(trab) overestimation therefore occurred in the phantoms with the lowest insert densities and highest shell thickness, where error was as high as 20 mg HA/cm3 (33%) in the radius phantom and 25 mg HA/cm(3) (41%) in the tibia phantom. Error in vBMD(trab) propagates to the calculation of micro-architectural measures; 41% error in vBMD(trab) will produce 41% error in volume fraction (BV/TV) and trabecular thickness (Tb.Th), and 5% error in trabecular separation (Tb.Sp). BHC algorithms supplied by the manufacturer failed to eliminate these errors. Our results confirm that geometric and densitometric variations influence the accuracy of HR-pQCT vBMD(trab) measurements, and must be considered when interpreting data across populations or time-points.

Figure 1

Idealized hydroxyapatite (HA) phantoms representative of the distal radius and tibia. Cortical thicknesses and diameters were based on measurements drawn from a dataset of healthy volunteers and osteoporotic patients. Outer shells representing cortical tissue have a density of 1200 mg HA/cm³ and thickness varying from 0.5 to 2.5 mm. Six removable inserts representing the trabecular compartment vary in density from 60 to 360 mg HA/cm³. (a) Photograph of the two phantoms (outer shells with 180 mg HA/cm³ inserts in place). (b) Single slice of the image data from the radius phantom (1.0 mm shell thickness, 60 mg HA/cm³ insert density) showing region of interest definition (dashed line).

Figure 2

Quantification of vBMD_trab measurement error. Percent error (top) and absolute error (bottom) are plotted against cortical thickness for each insert density (60 mg HA/cm³ through 360 mg HA/cm³). Phantoms were scanned in water and data was reconstructed using the 200 mg HA/cm³ beam hardening correction.

Figure 3

Effect of scanning medium on vBMD_trab measurement. Results are shown for the 180 mg HA/cm³ inserts with the 200 mg HA/cm³ beam hardening correction. Results for inserts of other densities follow the same trends (data not shown).

Figure 4

Spatial variation in vBMD_trab measurement for phantoms scanned in water with the 200 mg HA/cm³ correction. Percent error is plotted against percent of full diameter included in the analyzed region of interest (ROI). Measured vBMD_trab is highest at the periphery of the insert, decreasing towards the center of the cross-section. Results are shown for shell thicknesses of 1.0 mm (tibia) and 0.5 mm (radius) and for all insert densities (60 mg HA/cm³ through 360 mg HA/cm³). Results for all shell thicknesses follow the same trends (data not shown).

Figure 5

Effect of beam hardening correction (BHC) on vBMD_trab measurement in tibia and radius phantoms scanned in water. Percent error is plotted for each thickness of the phantom ‘cortical’ shell. These results are for the 240 mg HA/cm³ inserts. Results for inserts of other densities follow the same trends (data not shown).