Academic-Industrial Partnership for Translation of Acoustic Angiography

项目摘要 我们的目标是重新建立一个富有成效的合作，开发革命性的新的超声成像 硬件和处理方法。我们的创新技术实现了高信噪比和高 分辨率对比增强微血管成像。具体来说，我们开发了世界上第一个超宽带 同轴双频线性阵列，能够以低频发射超声， 微泡中的高频成分远远超过了7次谐波。这些传感器使 超谐波成像，其提供微脉管系统的高分辨率对比图像， 无组织背景，用于在动物和人体中显示100微米量级的血管 组织中值得注意的是，我们已经利用这些工具来成像微血管新生，几十年来， 是癌症的生物标志物，但以前不可能直接用超声成像。我们的'声学 血管造影成像很容易显示出微血管密度和结构的巨大差异， 恶性肿瘤和健康组织，为早期微小乳腺肿瘤提供上级敏感性和特异性 在遗传上易患乳腺癌的老鼠身上。此外，我们出色的超谐波信号分离 能够实现超分辨率成像，而不需要另外使用的麻烦的时空滤波方法 对于这个过程，其容易被组织运动或缓慢流动破坏。我们的下一代方法将 在深部组织（4-8 cm）中实现出色的微血管分辨率（<100 um），尽管微血管流动缓慢， 并且具有对组织运动的鲁棒性。尽管我们在硬件和成像技术方面取得了进步， 我们的技术仍然是人类癌症成像的最佳技术。阵列的浅焦深 在项目前期设计，受原型阵列和透镜设计的限制，并从他们的 原始的小动物成像应用程序，远远没有优化为3-4厘米的深度所需的图像可疑 人类的乳腺病变。在这次更新中，我们将指导双频的开发和优化， 专门用于更深临床成像的阵列（靶向深度高达8 cm）。我们的分辨率下降， 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 使用原型双频阵列，这种方法具有优异的结果，能够恢复低于100 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 在3D采集时提供最多的诊断信息，我们将开发第一个双频2D阵列。 这些目标的成功完成将使超声成像更接近于一种实用的临床模式， 以高特异性和灵敏度鉴定和评估癌症的血管生成和分子生物标志物， 未来的应用，如可疑病变的鉴别，对治疗反应的评估，以及早期诊断。 侦测结合硬件开发，优化声学参数，开发 波束成形和成像策略，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.