Toward Clinical Translation of Acoustic Angiography: Optimization of Microvascular Ultrasound Imaging on a Novel Dual-frequency Array

项目总结 乳腺癌是女性最常见的癌症，检测的主要方法是筛查。 乳房X光检查。通过乳房X光检查发现的可疑病变进一步通过二次成像进行评估 根据怀疑的严重程度，进行活体检查或手术。乳房X光检查已经成功 乳腺癌死亡率降低了20%，但导致乳腺癌的1-2%的乳房X光检查 活检，超过65%被确定为良性的。这表明绝大多数活组织检查是 不必要地执行，给患者造成不必要的身体、情感和经济上的痛苦。为了避免 发生不必要的活检时，必须提高二次乳腺成像的特异度，以准确 并且非侵入性地区分良恶性病变。恶性肿瘤的特征之一是 血管生成，从现有的血管中发展出新的血管，以满足癌症的快速生长 细胞。肿瘤相关血管生成导致与健康人截然不同的血管结构 组织，由曲折、混乱、漏水的血管主导。我们假设这些微血管特征 可作为恶性肿瘤的生物标志物。然而，缺乏高分辨率、安全、可接触的血管。 临床上的影像工具。在这里，我们的目标是修改和优化一种新的临床前成像技术，称为 “声学血管造影术”，临床使用。声学血管造影术(AA)是一种非侵入性、对比剂增强的 产生高分辨率(~150μm)三维微血管图的超声成像技术。 AA需要使用定制的双频(DF)单元件换能器，这严重限制了成像深度 (1.5厘米)，在与临床相关的对比剂剂量下敏感性较差。对于AA的临床翻译， DF换能器技术有待改进，必须根据临床参数进行优化。在这 我们建议使用一种新型的DF阵列换能器来提高AA的成像深度和灵敏度 实施临床优化的AA成像方案。利用体外实验，我们将评估信号 由超声造影剂生产，以确保最大限度地生成血管信号并优化 声学参数，如压力、波形形状和滤光片截止值，以最大化对比度与组织比。 所确定的最佳微泡参数和类型将在大鼠模型中进行活体验证 纤维肉瘤。我们预计，这项工作将促进AA在未来的临床翻译。

PROJECT SUMMARY Breast cancer is the most prevalent cancer in women, and the primary method of detection is screening mammography. Suspicious lesions identified via mammography are further evaluated with secondary imaging modalities and slated for biopsy or surgery based on the severity of suspicion. Mammography has successfully reduced the incidence of mortality due to breast cancer by 20%, but of the 1-2% of mammograms that lead to biopsy, more than 65% are determined to be benign. This indicates that a large majority of biopsies are performed unnecessarily, causing needless physical, emotional, and financial distress for patients. To avoid the occurrence of unnecessary biopsy, the specificity of secondary breast imaging must be improved to accurately and non-invasively differentiate benign from malignant lesions. One of the hallmarks of malignant cancer is angiogenesis, the development of new blood vessels from existing vessels to feed the rapid growth of cancer cells. Tumor-associated angiogenesis leads to very different vascular architecture than that found in healthy tissue, dominated by tortuous, chaotic, leaky vessels. We hypothesize that these microvascular characteristics can be used as a biomarker of malignancy. However, there is a lack of high-resolution, safe, accessible vascular imaging tools in the clinic. Here, we aim to modify and optimize a novel preclinical imaging technique, termed “acoustic angiography,” for clinical use. Acoustic angiography (AA) is a non-invasive, contrast-enhanced ultrasound imaging technique that produces high-resolution (~150 μm), three-dimensional microvascular maps. AA requires the use of custom dual-frequency (DF) single-element transducers that severely limit imaging depth (1.5 cm) and suffer from poor sensitivity at clinically-relevant contrast doses. For the clinical translation of AA, DF transducer technology must be improved, and the technique must be optimized at clinical parameters. In this work, we propose to improve the imaging depth and sensitivity of AA by using a novel DF array transducer to implement a clinically-optimized AA imaging scheme. Using in vitro experiments, we will evaluate signal production by ultrasound contrast agents to ensure maximum generation of vascular signatures and optimize acoustic parameters, such as pressure, waveform shape, and filter cutoffs, to maximize contrast-to-tissue ratio. The optimal parameters and type of microbubble that are determined will be validated in vivo in a rat model of fibrosarcoma. We anticipate that this work will facilitate impactful clinical translation of AA in the future.