Sources of Error and Improved Assessment of Trabecular Bone Structure Using In Vivo High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)
HR-pQCT enables noninvasive in vivo characterization of trabecular bone structure at peripheral sites. It can be a powerful tool for assessment of skeletal status and monitoring effect of therapy. The overall objective of this dissertation is two-fold: (i) to characterize errors in the indices describing trabecular structure introduced by partial volume averaging (PVA) and motion artifacts, and (ii) to develop a quantitative technique for estimating error introduced by motion image degradation and a regional analysis technique to account for the inherit spatial heterogeneity of bone structure at the distal radius and tibia.
The first study quantified the degree of error introduced to the topological indices of trabecular bone structure by PVA at in vivo resolution of 82 µm. The error in structure model index increased with resampled spatial resolution in a structure-type dependent manner. Connectivity density and degree of anisotropy were constantly underestimated at 82 µm.
The second study proposed a non-subjective technique for measuring subject motion, in which the parallelized projection images at 0° and 180° were compared using sum of squared intensity difference (SSD). SSD correlated strongly to motion-induced error in density, cortical geometric, and trabecular structural indices at the distal radius and tibia.
The third study characterized spatial variability in trabecular structure at the distal radius and tibia by subdividing the cross-section to eight subregions. In addition to substantial regional variations, the subregions with pronounced gender and age effects were identified.
The fourth study applied subregional analysis to a placebo-controlled randomized pilot study. Significant treatment effects on cortical geometry in the lateral quadrant of the distal radius and the posterior quadrant of the distal tibia were detected in subjects treated with an anti-fracture therapy (alendronate) for 2 years, which was not detected by conventional global analysis.
The results of this work provide a basis for understanding errors in trabecular indices derived from HR-pQCT images as well as a frame-work for quantitative motion detection and regional analysis. The results also serve as a guideline for standardizing protocols across studies, scanners, and study centers, to promote HR-pQCT as an effective tool for assessing skeletal status in research and clinical studies.