Accuracy of Peripheral Quantitative Computed Tomography (pQCT) For Assessing Area and Density of Mouse Cortical Bone

Department of Orthopaedic Surgery Barnes-Jewish Hospital at Washington University, Orthopaedic Research Laboratories, St. Louis, MO 63110, USA.
Calcified Tissue International (Impact Factor: 3.27). 11/2003; 73(4):411-8. DOI: 10.1007/s00223-002-0006-0
Source: PubMed


Peripheral quantitative computed tomography (pQCT) is increasingly used for measurement of cortical bone geometry and density in mice. We evaluated the accuracy of pQCT for area and density measurements of thin-walled aluminum phantoms and mouse femora. Aluminum tubes with varying wall thicknesses and femora from 1- to 6-month-old C3H/HeJ (C3H) and C57B1/6J (B6) mice (average cortical thickness 0.14-0.29 mm) were scanned at 70- or 90-microm resolution. pQCT values of area were compared to optical values determined after sectioning, while pQCT density (vBMD) was compared to solid aluminum density or correlated to bone ash content. For the aluminum phantoms, the error in pQCT area and density depended strongly on wall thickness, and density was consistently underestimated. For mouse femora, threshold values were found that produced zero error in bone area for each strain and age group, although the optimal threshold differed between groups. pQCT vBMD correlated strongly with ash content (r2=0.7), although the regression equations differed between strains and the magnitude of the inter-strain difference in vBMD was fourfold greater than the difference in ash content. This finding suggests that pQCT can overestimate the differences in volumetric mineral density between inbred mouse strains whose bones are of different thickness (e.g., C3H vs. B6). In conclusion, both area and density values obtained by pQCT depend strongly on specimen thickness, consistent with a partial volume averaging artifact. Investigators using pQCT to assess cortical bones in mice should be aware of the potential for cortical thickness-dependent errors.

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    • "[2] DXA measurements have been a valuable screening tool for bone diseases, but the accuracy of DXA measurements has been questioned and DXA cannot account for the three-dimensional architectural properties of bone.[2] [3] To overcome the challenges of DXA, peripheral quantitative computed tomography (pQCT) has been used to separate trabecular bone from cortical bone and estimate mechanical strength.[4] [5] While pQCT can assess both mineral content and structural properties in three dimensions from the same scan, its relatively low resolution can lead to errors when scanning small specimens [6] [7]. The resolution of microcomputed tomography (μCT) images is superior to clinical pQCT and, as a result, μCT has become the standard for accurate morphological and mineral density measurements in many pre-clinical studies [7]. "
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    ABSTRACT: Bone mineral density (BMD) measurements are critical in many research studies investigating skeletal integrity. For pre-clinical research, micro-computed tomography (microCT) has become an essential tool in these studies. However, the ability to measure the BMD directly from microCT images can be biased by artifacts, such as beam hardening, in the image. This three-part study was designed to understand how the image acquisition process can affect the resulting BMD measurements and to verify that the BMD measurements are accurate. In the first part of this study, the effect of beam hardening-induced cupping artifacts on BMD measurements was examined. In the second part of this study, the number of bones in the X-ray path and the sampling process during scanning was examined. In the third part of this study, microCT-based BMD measurements were compared with ash weights to verify the accuracy of the measurements. The results indicate that beam hardening artifacts of up to 32.6% can occur in sample sizes of interest in studies investigating mineralized tissue and affect mineral density measurements. Beam filtration can be used to minimize these artifacts. The results also indicate that, for murine femora, the scan setup can impact densitometry measurements for both cortical and trabecular bone and morphologic measurements of trabecular bone. Last, when a scan setup that minimized all of these artifacts was used, the microCT-based measurements correlated well with ash weight measurements (R(2)=0.983 when air was excluded), indicating that microCT can be an accurate tool for murine bone densitometry.
    Bone 08/2009; 45(6):1104-16. DOI:10.1016/j.bone.2009.07.078 · 3.97 Impact Factor
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    • "However, in contrast to the commonly reported volumetric mineral density (vBMD) values [2] [6] [30] the DMB we report here is not affected by structural properties. The differences in DMB of approximately 4% in cortical bone of B6 and C3H male mice are almost four-fold lower than the difference measured by pQCT in the same 6- month-old mice strains of these strains reported by Brodt et al. [30]. This difference in SR-μCT and pQCT values likely results from the difference in spatial resolution of the two techniques. "
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    ABSTRACT: 200-MHz scanning acoustic microscopy (SAM) and synchrotron radiation microCT (SR-microCT) were used to assess microstructural parameters, acoustic impedance Z and tissue degree of mineralization of bone (DMB) in site-matched regions of interest in femoral bone of two inbred strains. Transverse femoral sections taken from 5 C57BL/6J@Ico (B6) and 5 C3H/HeJ@Ico (C3H) mice (5.5 months old) were explored. Mass density rho, elastic coefficient c(11) and Young's modulus E(1) were locally derived in the distal epiphysis, distal metaphysis for trabecular bone and mid-diaphysis for cortical bone using a rule-of-mixture model. Structural parameter estimations obtained from X-ray tomographic and acoustic images were almost identical. Both strains had the same bone diameter, but the C3H mice had greater cortical thickness and smaller cancellous diameter than did B6 mice. The average DMB and impedance values were in the range between 1.13 and 1.33 g cm(-3) and 5.8 and 7.8 Mrayl, respectively. All tissue parameters were lower in B6 mice than in C3H mice. However, interstrain differences of DMB were much less (up to 3.8%) than differences of Z (up to 13.2%). SAM and SR-microCT fulfill the requirement for a simultaneous evaluation of cortical bone microstructure and material properties at the tissue level. However, SAM provides a quantitative estimate of elastic properties at the tissue level that cannot be captured by SR-microCT. The strong differences in the measured acoustic impedances among the two inbred strains indicate that the impedance is a good parameter to detect genetic variations of the skeletal phenotype in small animal models.
    Bone 01/2008; 41(6):1017-24. DOI:10.1016/j.bone.2007.08.042 · 3.97 Impact Factor
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    • "Two hundred-MHz SAM reveals the bone architecture with a resolution comparable to lCT [10] [14] and accurate morphological measurements can be performed on the impedance images. Our geometrical measurements of bone diameter and cortical width of the mid-diaphyseal femur fell in the range of previously reported values for these strains measured by means of lCT, pCT and histomorphometry [3] [15] [16]. In contrast to many previous studies on mice and, to the best of our knowledge, all ultrasound studies on small animal skeleton the high spatial resolution used here allowed an exclusion of small cavities and canals in the cortical layer. "
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    ABSTRACT: Two hundred-MHz time-resolved scanning acoustic microscopy was applied for the investigation of acoustic and structural bone properties of mice from two inbred strains. Transverse sections of femur taken from 5 C57BL/6J@Ico and 5 C3H/HeJ@Ico mice were explored. Both strains had the same bone diameter, but the C3H/HeJ@Ico mice had greater cortical thickness, smaller cancellous diameter, and greater acoustic impedance values than C57BL/6J@Ico mice. The strong differences in the measured acoustic impedances among the two inbred strains indicate that the impedance is a good parameter to detect genetic variations of the skeletal phenotype in small animal models.
    Ultrasonics 01/2007; 44 Suppl 1:e1307-11. DOI:10.1016/j.ultras.2006.05.032 · 1.94 Impact Factor
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