Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging,Volumetric Computed Tomography and Ultrasound

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bonemetastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrowcavity as well as for interaction of tumor and bone cells resulting in local bonedestruction. Our aim was to develop a model of experimental bone metastasis that allowsin vivo assessment of angiogenesis in skeletal lesions usingnon-invasive imaging techniques.For this purpose, we injected 10⁵ MDA-MB-231 human breast cancer cells intothe superficial epigastric artery, which precludes the growth of metastases in body areasother than the respective hind leg¹. Following 25-30 days after tumor cellinoculation, site-specific bone metastases develop, restricted to the distal femur,proximal tibia and proximal fibula¹. Morphological and functional aspects ofangiogenesis can be investigated longitudinally in bone metastases using magneticresonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).MRI displays morphologic information on the soft tissue part of bone metastases that isinitially confined to the bone marrow cavity and subsequently exceeds cortical bone whileprogressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data includingregional blood volume, perfusion and vessel permeability can be obtained andquantified^2-4. Bone destruction is captured in high resolution usingmorphological VCT imaging. Complementary to MRI findings, osteolytic lesions can belocated adjacent to sites of intramedullary tumor growth. After contrast agentapplication, VCT angiography reveals the macrovessel architecture in bone metastases inhigh resolution, and DCE-VCT enables insight in the microcirculation of theselesions^5,6. US is applicable to assess morphological and functional featuresfrom skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Dopplertechniques, structure and perfusion of the soft tissue metastases can be evaluated,respectively. DCE-US allows for real-time imaging of vascularization in bone metastasesafter injection of microbubbles⁷.In conclusion, in a model of site-specific breast cancer bone metastases multi-modalimaging techniques including MRI, VCT and US offer complementary information on morphologyand functional parameters of angiogenesis in these skeletal lesions.