Institute of Radiology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Maximiliansplatz 3, 91054 Erlangen, Germany; Institute of Radiology, University Hospital, Paracelsus University, Prof.-Ernst-Nathan-Str. 1, 90419 Nuremberg, Germany.
Institute of Radiology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Maximiliansplatz 3, 91054 Erlangen, Germany.
Bone. 2021 Mar;144:115821. doi: 10.1016/j.bone.2020.115821. Epub 2020 Dec 19.
The imaging of bone metastases, which is regularly performed by cross-sectional modalities, is clinically vital when characterizing and staging osseous lesions. In this paper, we aimed to establish a novel methodology using experimental ultrasound (US) techniques to assess the morphological, functional, and molecular features of breast cancer bone metastases in an animal model, compared with magnetic resonance imaging (MRI) and histological analysis.
Nude rats were implanted intra-arterially with MDA-MB-231 breast cancer cells to induce osteolytic metastasis in their right hind legs. Once tumors had developed, an experimental US technique using automatic 3D scanning and MRI were performed. For assessment of perfusion, functional imaging techniques included contrast-enhanced US (CEUS) and dynamic contrast-enhanced MRI (DCE-MRI). For molecular ultrasound, anti-VEGFR2 conjugated microbubbles were applied and correlated with immunostaining for VEGFR2 expression.
3D US enabled the automatic assessment of osteolytic lesions, including the largest tumor diameters along the x-, y- and z-axes as well as the segmented tumor volumes, without significant differences between US and MRI (p > 0.18). The CEUS and DCE-MRI of osseous lesions showed corresponding results for the parameters peak enhancement, wash-in area under the curve (both, r > 0.5) and wash-in perfusion index (r > 0.3) when differentiating between tumor, necrotic tissue and healthy muscle tissue (all, p < 0.01). Finally, molecular US allowed the non-invasive assessment of increased VEGFR2 expression in skeletal lesions compared with surrounding muscle tissue (p = 0.03), while a control antibody could not discriminate between these tissues (p = 0.44)-a factor which was confirmed by histological analysis.
To the best of our knowledge, this is the first report on an imaging protocol for breast cancer bone metastasis using an experimental US scanner. Therefore, we present a novel methodology to characterize these osseous lesions on the morphological, functional, and molecular level in correlation with MRI and histological analysis.
通过横断面模态进行的骨转移成像在对骨病变进行特征描述和分期时具有重要的临床意义。在本文中，我们旨在建立一种新的方法，使用实验性超声（US）技术来评估动物模型中乳腺癌骨转移的形态、功能和分子特征，与磁共振成像（MRI）和组织学分析进行比较。
裸鼠经动脉内植入 MDA-MB-231 乳腺癌细胞，以在其右后腿诱导溶骨性转移。一旦肿瘤发展，就会使用自动 3D 扫描和 MRI 进行实验性 US 技术。为了评估灌注，功能成像技术包括对比增强超声（CEUS）和动态对比增强 MRI（DCE-MRI）。对于分子超声，应用了抗 VEGFR2 缀合的微泡，并与 VEGFR2 表达的免疫染色相关联。
3D US 能够自动评估溶骨性病变，包括 x、y 和 z 轴上的最大肿瘤直径以及分割的肿瘤体积，与 US 和 MRI 之间没有显著差异（p > 0.18）。骨病变的 CEUS 和 DCE-MRI 显示，在区分肿瘤、坏死组织和健康肌肉组织时，峰值增强、曲线下面积（均 r > 0.5）和灌注指数（r > 0.3）的参数具有相应的结果（均 p < 0.01）。最后，分子 US 允许在骨骼病变中进行非侵入性的 VEGFR2 表达增加评估，与周围肌肉组织相比（p = 0.03），而对照抗体不能区分这些组织（p = 0.44）-这一因素通过组织学分析得到了证实。
据我们所知，这是第一篇关于使用实验性 US 扫描仪对乳腺癌骨转移进行成像方案的报告。因此，我们提出了一种新的方法，用于在与 MRI 和组织学分析相关的形态、功能和分子水平上对这些骨病变进行特征描述。
