Poor oxygenation of solid tumours has been linked with resistance to chemo- and radio-therapy and poor patient outcomes, hence non-invasive imaging of oxygen supply and demand in tumours could improve disease staging and therapeutic monitoring. Optoacoustic tomography (OT) is an emerging clinical imaging modality that provides static images of endogenous haemoglobin concentration and oxygenation. Here, we demonstrate oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualise the spatiotemporal heterogeneity of tumour vascular function. We show that tracking oxygenation dynamics using OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT. LNCaP tumours showed a spatially heterogeneous response within and between tumours, with a substantial but slow response to the gas challenge, aligned with ex vivo analysis, which revealed a generally perfused and viable tumour with marked areas of haemorrhage. PC3 tumours had a lower fraction of responding pixels compared to LNCaP with a high disparity between rim and core response. While the PC3 core showed little or no dynamic response, the rim showed a rapid change, consistent with our ex vivo findings of hypoxic and necrotic core tissue surrounded by a rim of mature and perfused vasculature. OE-OT metrics are shown to be highly repeatable and correlate directly on a per-tumour basis to tumour vessel function assessed ex vivo. OE-OT provides a non-invasive approach to reveal the complex dynamics of tumour vessel perfusion, permeability and vasoactivity in real time. Our findings indicate that OE-OT holds potential for application in prostate cancer patients, to improve delineation of aggressive and indolent disease as well as in patient stratification for chemo- and radio-therapy.

中文翻译：

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氧增强光声断层扫描 (OE-OT) 揭示了前列腺癌小鼠模型中的血管动力学

实体瘤氧合不良与对化疗和放疗的抵抗力以及患者预后不良有关，因此肿瘤中氧供需的非侵入性成像可以改善疾病分期和治疗监测。光声断层扫描 (OT) 是一种新兴的临床成像方式，可提供内源性血红蛋白浓度和氧合的静态图像。在这里，我们展示了氧增强 (OE)-OT，利用氧气挑战来可视化肿瘤血管功能的时空异质性。我们表明，使用 OE-OT 跟踪氧合动力学揭示了两种前列腺癌模型在具有显着不同血管功能（PC3 和 LNCaP）的裸鼠中的显着差异，这在静态 OT 中看起来相同。离体分析，揭示了一个普遍灌注且有活力的肿瘤，具有明显的出血区域。与 LNCaP 相比，PC3 肿瘤的响应像素比例较低，边缘和核心响应之间的差异很大。虽然 PC3 核心显示很少或没有动态响应，但边缘显示出快速变化，这与我们在体外发现的缺氧和坏死核心组织被成熟和灌注的脉管系统边缘包围的结果一致。OE-OT 指标被证明是高度可重复的，并且在每个肿瘤的基础上直接与离体评估的肿瘤血管功能相关。OE-OT 提供了一种非侵入性方法来实时揭示肿瘤血管灌注、通透性和血管活性的复杂动态。我们的研究结果表明，OE-OT 具有在前列腺癌患者中应用的潜力，可以改善侵袭性和惰性疾病的描述以及化学和放射治疗的患者分层。