良性和恶性乳腺肿瘤的磁共振成像非侵入性缺氧和新生血管评估的发展：初步结果。
Development of a Non-invasive Assessment of Hypoxia and Neovascularization with Magnetic Resonance Imaging in Benign and Malignant Breast Tumors: Initial Results.
机构信息
Institute of Medical Radiology, University Clinic of St. Pölten, Propst-Führer-Straße 4, St. Pölten, 3100, Austria.
Department of Neurosurgery, University of Erlangen-Nürnberg, Schwabachanlage 6, Erlangen, 91054, Germany.
出版信息
Mol Imaging Biol. 2019 Aug;21(4):758-770. doi: 10.1007/s11307-018-1298-4.
PURPOSE
To develop a novel magnetic resonance imaging (MRI) approach for the noninvasive assessment of hypoxia and neovascularization in breast tumors.
PROCEDURES
In this IRB-approved prospective study, 20 patients with suspicious breast lesions (BI-RADS 4/5) underwent multiparametric breast MRI including quantitative BOLD (qBOLD) and vascular architecture mapping (VAM). Custom-made in-house MatLab software was used for qBOLD and VAM data postprocessing and calculation of quantitative MRI biomarker maps of oxygen extraction fraction (OEF), metabolic rate of oxygen (MRO), and mitochondrial oxygen tension (mitoPO) to measure tissue hypoxia and neovascularization including vascular architecture including microvessel radius (VSI), density (MVD), and type (MTI). Histopathology was used as standard of reference. Appropriate statistics were performed to assess and compare correlations between MRI biomarkers for hypoxia and neovascularization.
RESULTS
qBOLD and VAM data with good quality were obtained from all patients with 13 invasive ductal carcinoma (IDC) and 7 benign breast tumors with a lesion diameter of at least 10 mm in all spatial directions. MRI biomarker maps of oxygen metabolism and neovascularization demonstrated intratumoral spatial heterogeneity with a broad range of biomarker values. Bulk tumor neovasculature consisted of draining venous microvasculature with slow flowing blood. High OEF and low mitoPO were associated with low MVD and vice versa. The heterogeneous pattern of MRO values showed spatial congruence with VSI. IDCs showed significantly higher MRO (P = 0.007), lower mitoPO (P = 0.021), higher MVD (P = 0.005), and lower (i.e., more pathologic) MTI (P = 0.001) compared with benign breast tumors. These results indicate that IDCs consume more oxygen and are more hypoxic and neovascularized than benign tumors.
CONCLUSIONS
We developed a novel MRI approach for the noninvasive assessment of hypoxia and neovascularization in benign and malignant breast tumors that can be easily integrated in a diagnostic MRI protocol and provides insight into intratumoral heterogeneity.
目的
开发一种新的磁共振成像（MRI）方法，用于无创评估乳腺肿瘤的缺氧和新生血管形成。
方法
在这项经过机构审查委员会批准的前瞻性研究中，20 名患有可疑乳腺病变（BI-RADS 4/5）的患者接受了多参数乳腺 MRI 检查，包括定量血氧水平依赖（qBOLD）和血管结构成像（VAM）。使用定制的内部 MatLab 软件进行 qBOLD 和 VAM 数据后处理，并计算氧摄取分数（OEF）、氧代谢率（MRO）和线粒体氧张力（mitoPO）的定量 MRI 生物标志物图，以测量组织缺氧和新生血管形成，包括血管结构，包括微血管半径（VSI）、密度（MVD）和类型（MTI）。组织病理学作为参考标准。进行了适当的统计学分析，以评估和比较缺氧和新生血管形成的 MRI 生物标志物之间的相关性。
结果
所有患者均获得了高质量的 qBOLD 和 VAM 数据，包括 13 例浸润性导管癌（IDC）和 7 例良性乳腺肿瘤，所有空间方向的病变直径均至少为 10mm。氧代谢和新生血管形成的 MRI 生物标志物图显示肿瘤内存在广泛的生物标志物值的空间异质性。肿块内新生血管主要由血流缓慢的引流静脉微血管组成。高 OEF 和低 mitoPO 与低 MVD 相关，反之亦然。MRO 值的异质模式与 VSI 具有空间一致性。IDC 与良性乳腺肿瘤相比，MRO 显著升高（P=0.007），mitoPO 显著降低（P=0.021），MVD 显著升高（P=0.005），病理性 MTI 降低（P=0.001）。这些结果表明，与良性肿瘤相比，IDC 消耗更多的氧气，并且更缺氧和新生血管形成。
结论
我们开发了一种新的 MRI 方法，用于无创评估良性和恶性乳腺肿瘤的缺氧和新生血管形成，该方法可以很容易地整合到诊断性 MRI 方案中，并提供对肿瘤内异质性的深入了解。
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