Academic-Industrial Partnership for Translation of Acoustic Angiography

项目总结 我们的目标是更新已经开发出革命性的新型超声成像的高效合作 硬件和处理方法。我们的创新技术使高信噪比和高信噪比 分辨率对比增强的微血管成像。具体地说，我们开发了世界上第一个超宽带 同轴双频线阵，可实现低频超声波发射和接收 来自微泡的高频成分远远超出了它们的7次谐波。这些传感器使 超谐成像，提供微血管的高分辨率对比度图像，基本上 没有组织背景，用于在动物和人类中显示100微米量级的血管 纸巾。值得注意的是，我们已经利用这些工具来成像微血管生成，几十年来已知的 成为癌症的生物标记物，但以前不可能直接用超声波成像。我们的声学 血管造影术的成像很容易显示出在微血管密度和结构上的巨大差异 恶性肿瘤和健康组织，为早期微小乳腺肿瘤提供了卓越的敏感性和特异性 在遗传上易患乳腺癌的小鼠身上。此外，我们出色的超谐信号分离 无需使用繁琐的时空滤波方法即可实现超分辨率成像 对于这个很容易被组织运动或缓慢流动破坏的过程。我们的下一代方法将 在深层组织(4-8厘米)实现出色的微血管分辨率(&lt；100um)，尽管微血管流动缓慢， 并且对组织运动具有健壮性。尽管我们在硬件和成像技术方面取得了进步，但挑战 使我们的技术成为成像人类癌症的最佳选择。阵列的浅焦深 在之前的项目期间设计，受原型阵列和镜头设计的限制，并从他们的 最初的小动物成像应用程序，远远不能优化到需要3-4厘米深的可疑图像 人类的乳房病变。在这次更新中，我们将指导双频的开发和优化 专为更深的临床成像(目标深度可达8厘米)而设计的阵列。我们因较低的分辨率而损失 频率带宽将通过超谐波超分辨率处理来恢复。我们已经证明了 这种方法使用原型双频阵列取得了很好的效果，使恢复达到了100以下 微米分辨率，即使频率可以穿透6-8厘米。此外，由于微血管成像 提供最多的诊断信息当以3D方式获取时，我们将开发第一个双频2D阵列。 这些目标的成功实现将推动超声成像更接近于实用的临床模式 识别和评价肿瘤血管生成和分子生物标志物的高特异性和敏感性 未来的应用，如可疑病变的鉴别，治疗反应的评估，以及早期 侦测。结合硬件开发，我们将优化声学参数，开发 波束形成和成像策略，以及在临床前和临床人群中的测试性能。

PROJECT SUMMARY We aim to renew a highly productive collaboration that has developed revolutionary new ultrasound imaging hardware and processing approaches. Our innovative technologies have enabled high-signal-to-noise and high- resolution contrast-enhanced microvascular imaging. Specifically, we developed the world’s first ultra-broadband co-axial dual-frequency linear arrays, which enable transmission of ultrasound at low frequencies and reception of high-frequency content from microbubbles well beyond their 7th harmonic. These transducers enable superharmonic imaging, which provides high-resolution contrast images of the microvasculature with essentially no tissue background and is used for visualizing vessels on the order of 100 microns in both animal and human tissues. Significantly, we have utilized these tools to image microvascular angiogenesis, known for decades to be a biomarker of cancer, yet not previously possible to image directly with ultrasound. Our ‘acoustic angiography’ imaging readily shows drastic differences in microvasculature density and structure between malignant cancers and healthy tissue, providing superior sensitivity and specificity to early micro-breast tumors in mice genetically predisposed to breast cancer. Furthermore, our excellent superharmonic signal separation enables super-resolution imaging without the cumbersome spatiotemporal filtering approaches otherwise used for this process, which are readily corrupted by tissue motion or slow flow. Our next generation approach will enable outstanding microvascular resolution (<100 um) in deep tissue (4-8 cm), despite slow microvascular flow, and with robustness to tissue motion. Despite our advances in hardware and imaging techniques, challenges remain to make our technology optimal for imaging human cancers. The shallow focal depth of the arrays designed in the prior project period, limited by prototype array and lens designs, and carried over from their original small-animal imaging applications, is far from optimized for the 3-4 cm depth needed to image suspicious breast lesions in humans. In this renewal, we will direct the development and optimization of dual-frequency arrays specifically for deeper clinical imaging (targeting depths up to 8cm). Our loss in resolution due to lower frequency bandwidths will be recovered by superharmonic super-resolution processing. We have demonstrated this approach with excellent results using the prototype dual frequency arrays, enabling recovery of sub-100 micron resolution, even with frequencies that can penetrate 6-8 cm. Furthermore, since microvascular imaging provides the most diagnostic information when acquired in 3D, we will develop the first dual-frequency 2D arrays. Successful completion of these aims will advance ultrasound imaging closer to a practical clinical modality for identifying and assessing angiogenic and molecular biomarkers of cancer with high specificity and sensitivity for future applications such as differentiation of suspicious lesions, assessment of response to therapy, and early detection. Combined with the hardware development, we will optimize acoustic parameters, develop beamforming and imaging strategies, and test performance in preclinical and clinical populations.