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Tobias B?uerle Dorde Komljenovic Martin R. Berger Wolfhard Semmler 《Journal of visualized experiments : JoVE》2012,(66)
Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone
metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow
cavity as well as for interaction of tumor and bone cells resulting in local bone
destruction. Our aim was to develop a model of experimental bone metastasis that allows
in vivo assessment of angiogenesis in skeletal lesions using
non-invasive imaging techniques.For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into
the superficial epigastric artery, which precludes the growth of metastases in body areas
other than the respective hind leg1. Following 25-30 days after tumor cell
inoculation, site-specific bone metastases develop, restricted to the distal femur,
proximal tibia and proximal fibula1. Morphological and functional aspects of
angiogenesis can be investigated longitudinally in bone metastases using magnetic
resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).MRI displays morphologic information on the soft tissue part of bone metastases that is
initially confined to the bone marrow cavity and subsequently exceeds cortical bone while
progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including
regional blood volume, perfusion and vessel permeability can be obtained and
quantified2-4. Bone destruction is captured in high resolution using
morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be
located adjacent to sites of intramedullary tumor growth. After contrast agent
application, VCT angiography reveals the macrovessel architecture in bone metastases in
high resolution, and DCE-VCT enables insight in the microcirculation of these
lesions5,6. US is applicable to assess morphological and functional features
from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler
techniques, structure and perfusion of the soft tissue metastases can be evaluated,
respectively. DCE-US allows for real-time imaging of vascularization in bone metastases
after injection of microbubbles7.In conclusion, in a model of site-specific breast cancer bone metastases multi-modal
imaging techniques including MRI, VCT and US offer complementary information on morphology
and functional parameters of angiogenesis in these skeletal lesions. 相似文献