Peña Jaime A, Barkmann Reinhard, Reinhold Stefan, Damm Timo, Fricke Tobias, Bastgen Jan, Thomsen Felix, Glüer Claus-C
Section Biomedical Imaging, Department of Radiology and Neuroradiology University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
Section Biomedical Imaging, Department of Radiology and Neuroradiology University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
Z Med Phys. 2025 May 2. doi: 10.1016/j.zemedi.2025.04.002.
Quantitative Computed Tomography (QCT) has not fully addressed the need to reduce intra- and inter-scanner variability for Osteoporosis and bone-related studies, which can lead to inaccuracies when pooling data from different CT manufacturers, models, devices, or protocols. In this context, the aim of this work was to develop ex vivo methods for the standardization of bone mineral density and microstructural parameters.
Six human vertebral body specimens embedded in poly-methyl methacrylate (PMMA) were scanned ex vivo inside an anthropomorphic abdomen phantom in eight different CT-scanners. We measured 3D trabecular and cortical bone mineral density (Tb.BMD and Ct.BMD at the peeled spongiosa and the vertical cortex, respectively), trabecular separation (Tb.Sp) and cortical thickness (Ct.Th). Standardization of Tb.BMD and Ct.BMD across CT-scanners was conducted by correcting for the influence of PMMA and kernel related differences in the segmented cortical volume. For Tb.BMD and Ct.BMD two CT-scanners, where the majority of the patients were scanned, were used as reference. For Tb.Sp standardization we accounted for the image binarization threshold and used high-resolution peripheral QCT (HR-pQCT) as reference. Cross-calibration factors were obtained for each CT-scanner from which the cross-calibrated measures xTb.BMD, xCt.BMD and xTb.Sp were computed both ex vivo and in vivo. Agreement of the ex vivo measurements with respect to the references was quantified with Lin's concordance correlation coefficient (r) before and after standardization. For the clinical in vivo part of the study, 152 patients (24M, 128F) undergoing long-term bisphosphonate treatment had their T12 or L1 vertebrae scanned with the same CT-scanners and protocols as for ex vivo. Statistical bone fracture models were conducted before and after cross-calibration to assess the performance of the standardization procedure in vivo.
After cross-calibration the overall ex vivo mean Tb.BMD across CT-scanners was basically maintained, changing only from 119.0 mgHA/cm to 119.4 mgHA/cm. The mean Ct.BMD raised from 420.4 mgHA/cm to 441.1 mgHA/cm. Tb.BMD showed a small variability (SD of means) across centers of 2.7 mgHA/cm. For Ct.BMD additional kernel related thickness correction reduced this variability from 31.7 mgHA/cm to 22.4 mgHA/cm. Non-standardized Tb.Sp showed a mean of 2.63 mm across CT-scanners, which after standardization was corrected to 1.18 mm. Agreement to the reference measurements was markedly improved after standardization (before: the r [min, max] for Tb.BMD, Ct.BMD and Tb.Sp was [0.64, 0.92], [0.40, 0.89] and [0.57, 0.99], respectively; after standardization: [0.98, 0.99], [0.96, 0.99] and [0.78, 0.99], respectively). For in vivo, Tb.BMD and Ct.BMD showed a mean (SD of means) across CT-scanners before standardization of 72.3 (7.6) mgHA/cm and 352.4 (44.6) mgHA/cm, respectively and after standardization 72.6 (7.0) mgHA/cm and 370.7 (31.0) mgHA/cm, respectively. Non-standardized Tb.Sp showed a mean (SD of means) of 3.55 (2.42) mm across CT-scanners, which after standardization was corrected to 1.65 mm (0.16) mm. The cross-calibrated xTb.BMD showed a highly statistical significance in prevalent fracture classification (p = 0.0001) similar to Tb.BMD (p = 0.0002). For xCt.BMD a trend was observed in improving fracture prediction, albeit not significant (p = 0.14), compared to Ct.BMD (p = 0.23). xTb.Sp demonstrated improved fracture prediction (p = 0.024) compared to a non-standardized Tb.Sp (p > 0.1).
The improved inter-scanner agreement with corresponding reduced variability underscores the importance of cross-calibration of bone mineral density and microstructural parameters. For the in vivo application of the methods, cross-calibrated Tb.Sp improved fracture prediction in patients, whereas cross-calibrated BMD had no discernible impact, possibly due to the distribution of patients across the participating CT-centers and the already high fracture classification power of Tb.BMD.
定量计算机断层扫描（QCT）尚未充分满足骨质疏松症和骨相关研究中减少扫描仪内和扫描仪间变异性的需求，当汇总来自不同CT制造商、型号、设备或协议的数据时，这可能导致不准确。在此背景下，本研究的目的是开发用于骨密度和微观结构参数标准化的离体方法。
将六个嵌入聚甲基丙烯酸甲酯（PMMA）的人体椎体标本在拟人化腹部模型内进行离体扫描，使用八台不同的CT扫描仪。我们测量了三维小梁和皮质骨密度（分别为去皮松质骨和垂直皮质处的Tb.BMD和Ct.BMD）、小梁间距（Tb.Sp）和皮质厚度（Ct.Th）。通过校正PMMA的影响以及分割皮质体积中与内核相关的差异，对不同CT扫描仪之间的Tb.BMD和Ct.BMD进行标准化。对于Tb.BMD和Ct.BMD，将大多数患者进行扫描的两台CT扫描仪用作参考。对于Tb.Sp标准化，我们考虑了图像二值化阈值，并使用高分辨率外周QCT（HR-pQCT）作为参考。为每个CT扫描仪获得交叉校准因子，据此计算离体和体内的交叉校准测量值xTb.BMD、xCt.BMD和xTb.Sp。在标准化前后，使用林氏一致性相关系数（r）对离体测量值与参考值的一致性进行量化。对于该研究的临床体内部分，152名接受长期双膦酸盐治疗的患者（24名男性，128名女性）的T12或L1椎体使用与离体扫描相同的CT扫描仪和协议进行扫描。在交叉校准前后进行统计骨折模型分析，以评估体内标准化程序的性能。
交叉校准后，不同CT扫描仪之间离体Tb.BMD的总体平均值基本保持不变，仅从119.0 mgHA/cm变为119.4 mgHA/cm。平均Ct.BMD从420.4 mgHA/cm提高到441.1 mgHA/cm。Tb.BMD在各中心之间显示出较小的变异性（平均值的标准差），为2.7 mgHA/cm。对于Ct.BMD，额外的与内核相关的厚度校正将这种变异性从31.7 mgHA/cm降低到22.4 mgHA/cm。未标准化的Tb.Sp在不同CT扫描仪之间的平均值为2.63 mm，标准化后校正为1.18 mm。标准化后与参考测量值的一致性显著提高（之前：Tb.BMD、Ct.BMD和Tb.Sp的r[最小值，最大值]分别为[0.64，0.92]、[0.40，0.89]和[0.57，0.99]；标准化后：分别为[0.98，0.99]、[0.96，0.99]和[0.78，0.99]）。对于体内情况，标准化前不同CT扫描仪之间Tb.BMD和Ct.BMD的平均值（平均值的标准差）分别为72.3（7.6）mgHA/cm和352.4（44.6）mgHA/cm，标准化后分别为72.6（7.0）mgHA/cm和370.7（31.0）mgHA/cm。未标准化的Tb.Sp在不同CT扫描仪之间的平均值（平均值的标准差）为3.55（2.42）mm，标准化后校正为1.65（0.16）mm。交叉校准后的xTb.BMD在 prevalent骨折分类中显示出高度统计学意义（p = 0.0001），与Tb.BMD相似（p = 0.0002）。对于xCt.BMD，与Ct.BMD相比，观察到骨折预测有改善趋势，尽管不显著（p = 0.14）（p = 0.23）。与未标准化的Tb.Sp相比，xTb.Sp显示出改善的骨折预测（p = 0.024）（p > 0.1）。
扫描仪间一致性的提高以及相应变异性的降低强调了骨密度和微观结构参数交叉校准的重要性。对于这些方法的体内应用，交叉校准的Tb.Sp改善了患者的骨折预测，而交叉校准的BMD没有明显影响，这可能是由于患者在参与的CT中心之间的分布以及Tb.BMD已经很高的骨折分类能力。
