Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2*discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameterfIVIMdiscriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis.
肿瘤新生血管生成是癌症进展的重要标志，由缺氧肿瘤微环境的选择性压力交替触发。结合血氧水平依赖（BOLD）MRI（描绘血氧饱和度）和体素内不相干运动（IVIM）MRI（捕捉血管内和血管外扩散）的无创、无对比剂多参数MRI，可同时提供肿瘤氧合和新血管生成的深入信息。我们的目标是识别能够预测缺氧诱导血管生成的影像标志物，并通过多重免疫组化分析验证我们的发现。我们进行了一项体内研究，涉及36只接种了管腔A型、Her2+和三阴性乳腺癌细胞的雌性无胸腺裸鼠。我们使用高场9.4特斯拉MRI系统进行成像，随后使用针对CD-31、PDGFR-β和Hif1-α的多重免疫组化分析肿瘤。我们发现，高氧BOLD MRI衍生的参数ΔR2*能够区分管腔A型与Her2+和三阴性乳腺癌，而IVIM衍生的参数fIVIM能够区分管腔A型和Her2+与三阴性乳腺癌。对多参数MRI和多重免疫组化数据进行主成分分析的综合分析，突显了三阴性和管腔A型乳腺癌之间的差异。我们得出结论，结合高氧BOLD MRI和IVIM MRI的多参数MRI，无需对比剂，为评估缺氧诱导的血管生成提供了有前景的无创标志物。
肿瘤(癌症)患者之家