Imaging Cancer Angiogenesis with Acoustic Angiography Ultrasound

摘要 早期发现是抗击癌症的关键组成部分，它比早期发现更能带来更好的生存机会。 当肿瘤被诊断为晚期时。然而，随着医生们的目标是检测出越来越小的 对于肿瘤，现代成像手段的分辨率和灵敏度变得有问题。因此，在这个 项目，我假设肿瘤可以通过可视化基础血管的结构来检测 使用一种名为声学血管造影术的新超声技术，该技术是在Paul Dayton博士的 实验室。血管生成，即从现有血管生长出来的新血管，是由不断生长的肿瘤刺激的。 因为它们需要新的血管系统来供应它们的快速生长。然而，形成的新血管并不会成为 成熟、健康的血管系统。相反，肿瘤血管是漏水的，杂乱无章的，并且经常形成弯曲的和 扭曲的形态。声学血管造影术使我们能够使用微泡造影剂和新型超声 将直径至少为100μm的血管系统可视化并评估个人曲折程度的技术 血管。 在这个项目中，我将在一个三阴性乳腺癌模型中描述肿瘤发展的曲折过程。 并将其与正常血管进行比较。肿瘤应该有更高的血管密度和 由于肿瘤生长引起的血管生成异常猖獗，比健康组织更加曲折。 此外，我将评估基于声学血管成像图像的肿瘤检测的最低限度 评价图像分类准确性的放射学阅读器研究和定量肿瘤检测模型 (作为肿瘤或健康)用于不同大小的肿瘤。我们还将确定分子标记的分布是否 使用分子声学血管造影术，血管生成的程度与可见的曲折有关。最后，我们将评估 声学血管造影术对影像患者可疑乳腺病变成像的临床可行性 在活检前对BI-RADS4和5个病变进行检查，并进行读数研究以确定声学血管造影 比传统的超声波具有更好的诊断功能，目的是最终避免不必要的 活组织检查。 我的论文研究的最终结果将决定声学揭示的血管曲折是否 血管造影术超声图像可以用来检测肿瘤，并将建立最小可检测到的肿瘤 尺码。此外，它还将把血管生成的分子成像与血管的曲折联系起来。未来研究 方向包括加深我对血管生成的细胞和分子机制的理解 在补充成像模式下进行培训。

ABSTRACT Early detection is a critical component of the fight against cancer, and it results in better chances of survival than when tumors are diagnosed at advanced stages. However, as physicians aim to detect increasingly smaller tumors, the resolution and sensitivity of modern imaging modalities become problematic. Therefore, in this project, I hypothesize that tumors can be detected by visualizing the structure of the underlying blood vessels using a novel ultrasound technique called acoustic angiography which was developed in Dr. Paul Dayton’s laboratory. Angiogenesis, the growth of new blood vessels from existing ones, is stimulated by growing tumors as they require new vasculature to supply their rapid growth. However, the new vessels that form do not become mature, healthy vasculature. Instead, tumor vessels are leaky, disorganized, and often shaped into bent and twisted forms. Acoustic angiography allows us to use microbubble contrast agents and novel ultrasound technology to visualize vasculature at least 100 μm in diameter and assess the degree of tortuosity of individual blood vessels. In this project, I will characterize the tortuosity of developing tumors in a model of triple-negative breast cancer and compare it to that of normal blood vessels. Tumors are expected to have higher vascular density and tortuosity than healthy tissue because of the rampant, abnormal angiogenesis induced by tumor growth. Additionally, I will evaluate the minimum limit of tumor detection based on acoustic angiography images using a radiology reader study and a quantitative tumor detection model to evaluate the accuracy of image classification (as tumor or healthy) for tumors of different sizes. We will also determine if the distribution of molecular markers of angiogenesis is correlated to visible tortuosity using molecular acoustic angiography. Finally, we will evaluate the clinical feasibility of using acoustic angiography for imaging suspicious breast lesions by imaging patients with BI-RADS 4 and 5 lesions prior to biopsy and performing a reader study to determine if acoustic angiography has superior diagnostic utility than traditional ultrasound, with the goal of eventually avoiding unnecessary biopsies. The final results of my dissertation research will determine whether vascular tortuosity revealed by acoustic angiography ultrasound images can be used to detect tumors, and will establish the minimum detectable tumor size. Furthermore, it will also correlate molecular imaging of angiogenesis to vascular tortuosity. Future research directions include deepening my understanding of the cellular and molecular mechanisms of angiogenesis and training in a complementary imaging modality.