Section Biomedical Imaging, Department of Radiology and Neurology, University Hospital Schleswig-Holstein, Kiel, Germany.
Institute of Biomechanics, Hamburg University of Technology (TUHH), Hamburg, Germany.
J Bone Miner Res. 2018 Mar;33(3):410-418. doi: 10.1002/jbmr.3317. Epub 2017 Nov 17.
The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly-localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro-computed tomography (μCT) within in vivo mouse datasets. Two Balb/c nude datasets were used: (i) bone-homing MDA-MB-231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle, and weekly μCT (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into the right tibia and weekly μCT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150 μm) from the nearest follow-up. Osteosclerotic lesions were determined by measuring the distance from each follow-up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed 1 week after tumor cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes. Lesion volume was smaller in the alendronate versus control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data show that quantification of local structural change with serial μCT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. © 2017 American Society for Bone and Mineral Research.
肿瘤细胞转移到骨骼会导致溶骨性和成骨性病变，分别导致严重的、高度局限的骨破坏和异常的骨形成。准确量化病变进展对于理解潜在机制和评估治疗效果至关重要；然而，标准结构参数可能对局部变化不敏感。我们使用活体小鼠数据集内的微计算机断层扫描（μCT）开发了量化溶骨性和成骨性病变的方法。使用了两个 Balb/c 裸鼠数据集：（i）注射到左心室的骨归巢 MDA-MB-231（溶骨性）细胞，用阿伦膦酸盐或载体处理，并每周进行 μCT（胫骨近端）扫描 4 周，和（ii）注射到右胫骨的 MCF7（成骨性）细胞，并在 12 周内每周进行 μCT 扫描。在将图像注册到基线后，通过将距离最近的随访距离大于阈值（150μm）的所有基线骨体素相加来确定溶骨性病变体积。成骨性病变通过测量每个随访表面体素到最近的基线表面的距离，并计算周围体素的距离值（SDDT）的标准差来确定。测定骨矿物质密度（BMD）、骨体积密度（BV/TV）和分离度（Sp）进行比较。肿瘤细胞注射后 1 周即可观察到溶骨性病变；然而，没有观察到相应的 BV/TV 损失或 Sp 增加，表明标准参数无法检测到早期转移变化。与对照组相比，阿伦膦酸盐组的病变体积更小（第 3 周和第 4 周对照组病变体积的 15.0%，p=0.004 和 18.6%，p=0.002）。在成骨性病变数据集中，注射后 SDDT 增加，为成骨性骨形成提供了一种新的潜在测量方法。这些数据表明，使用连续 μCT 对局部结构变化进行定量可能克服标准矿物质和微观结构参数的局限性，并成功区分转移和正常的骨转换。
