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Abstract：
Ultrasound localization microscopy can image microvasculature in vivo without sacrificing imaging penetration depth. However, the reliance on super-resolution inference limits the applicability of the technique because subpixel tissue motion can corrupt microvascular reconstruction. Consequently, the majority of previous pre-clinical research on this super-resolution procedure has been restricted to low-motion experimental models with ample motion correction or data rejection, which precludes the imaging of organ sites that exhibit a high degree of respiratory and other motion. In this article, we present a novel anesthesia protocol in rabbits that induces safe, controllable periods of apnea to enable the long image-acquisition times required for ultrasound localization microscopy. We apply this protocol to a VX2 liver tumor model undergoing sorafenib therapy and compare the results to super-resolution images from conventional high-dose isoflurane anesthesia. We find that the apneic protocol was necessary to correctly identify the poorly vascularized tumor cores, as verified by immunohistochemistry, and to reveal the tumoral microvascular architecture.
摘要：
超声定位显微镜可以在不牺牲成像穿透深度的情况下对体内微血管成像。然而,由于亚像素组织运动会破坏微血管重建，因此对超分辨率推断的依赖限制了该技术的适用性。因此,以前关于这种超分辨率程序的大多数临床前研究仅限于具有足够运动校正或数据排斥的低运动实验模型，这排除了对表现出高度呼吸和其他运动的器官部位的成像。在这篇文章中,我们提出了一种新的麻醉方案，在兔子中诱导安全，可控制的呼吸暂停周期，以实现超声定位显微镜所需的长时间图像采集。我们将此方案应用于接受索拉非尼治疗的VX2肝肿瘤模型，并将结果与常规高剂量异氟醚麻醉的超分辨率图像进行比较。我们发现，呼吸暂停方案对于正确识别血管化不良的肿瘤核心是必要的，如免疫组织化学所证实，并揭示肿瘤的微血管结构。
