Improving thyroid cancer management using high-frequency quantitative ultrasound

描述(由申请人提供)：拟议研究的长期目标是通过使用高频定量超声(QUS)对癌症进行非侵入性检测和分类，显著改善甲状腺结节的管理。根据一项研究，在临床评估中发现的可疑甲状腺结节的数量高达成年人口的70%。据估计，仅在美国，今年就将进行30多万例甲状腺细针抽吸(FNA)活检。对甲状腺结节进行FNA需要护理医生的时间和服务，病理学家的时间和服务，以及患者的时间、不适和焦虑。然而，绝大多数接受FNA的甲状腺结节最终被证明是良性的。高频QUS成像的发展几乎肯定会减少患者的压力、不适和焦虑，并可以通过减少许多FNA程序的必要性而显著减轻病理学家的负担。此外，如果能够开发出一种定量的、不依赖于操作员的新型成像系统，该设备的实用将改善那些由于患者工作量较小而专业知识不是那么渊博的机构的护理。对于大多数甲状腺结节，常规超声成像不能给出明确的诊断。我们假设高频QUS将通过提供多达六个与组织微结构相关的独立定量参数来实现对甲状腺癌的非侵袭性诊断，并显著改善甲状腺结节的管理。为了验证高频QUS可以改善甲状腺结节管理的假设，提出了两个具体目标。第一个具体目标是使用三维阻抗图(3DZM)方法建立正常甲状腺、良性甲状腺病变和恶性甲状腺病变的组织散射和QUS模型。光学显微镜和由此产生的3DZM将被用来在动物模型中构建甲状腺癌组织散射的新模型，并识别将由QUS估计描述的结构。通过将使用3DZMS的预测超声信号与来自相同组织的实际测量信号进行比较，可以识别散射源。此外，微观组织对散射和后续超声信号的作用将通过3DZMS来确定。第二个具体目标是展示QUS成像技术在体内从甲状腺癌动物模型中对良性、癌性和癌症类型的结节进行分类的能力。将对小鼠的正常甲状腺、良性甲状腺结节和癌性甲状腺病变进行检查，并应用QUS技术来确定体内病变的分类能力。诊断将通过肿瘤的光学显微镜照片和独立的病理报告来确认。然后，光学显微照相将被并入第一个具体目标，作为识别散射源和建立更灵敏的量子散射模型的迭代技术。与公共卫生相关：多达70%的成年人患有可检测到的甲状腺结节，对这些结节的适当管理造成了危机。高频定量超声可提供多达6个与甲状腺结节组织微结构相关的独立参数。高频定量超声提供的更多的诊断信息将极大地改善甲状腺结节的管理危机。

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to significantly improve the management of thyroid nodules through non-invasive detection and classification of cancer using high-frequency quantitative ultrasound (QUS). According to one study, the number of suspect thyroid nodules detected in clinical evaluations is up to 70% of the adult population. It is estimated that more than 300,000 fine needle aspiration (FNA) biopsies of the thyroid will be conducted this year in the United States alone. FNA performed on thyroid nodules requires the time and services of the point-of-care physician, the time and services of a pathologist, and time, discomfort, and anxiety of the patient. However, a vast majority of thyroid nodules undergoing FNA turn out to be benign. The development of high-frequency QUS imaging will almost certainly decrease the stress, discomfort, and anxiety of the patient and could markedly reduce the burden of pathologists by reducing the necessity of many FNA procedures. Furthermore, if a novel imaging system could be developed that was quantitative and operator independent, the utility of the device would improve care in facilities where expertise is not as profound due to smaller patient loads. For most thyroid nodules, conventional ultrasonic imaging is unable to give a definitive diagnosis. We hypothesize that high-frequency QUS will allow the diagnosis of thyroid cancer non-invasively and significantly improve management of thyroid nodules by providing up to six independent quantitative parameters related to the tissue microstructure. To test the hypotheses that high-frequency QUS can improve the management of thyroid nodules, two specific aims are proposed. The first specific aim is to develop models of tissue scattering and QUS from normal thyroid, benign thyroid lesions, and malignant thyroid lesions using a three-dimensional impedance map (3DZM) approach. Optical photomicrographs and resulting 3DZMs will be used to construct new models for tissue scattering from thyroid cancer in the animal models and to identify structures that will be described by QUS estimates. By comparing predicted ultrasonic signals using the 3DZMs with actual measured signals from the same tissue, the source of scattering can be identified. Furthermore, the role of the microstructural organization to scattering and the subsequent ultrasonic signal will be determined through 3DZMs. The second specific aim is to demonstrate the ability of QUS imaging techniques to classify nodules for benign, cancerous, and type of cancer in vivo from animal models of thyroid cancer. Normal thyroid, benign thyroid nodules, and cancerous thyroid lesions in mice will be examined and QUS techniques applied to determine the capability to classify the lesions in vivo. Diagnosis will be confirmed via optical photomicrographs of the tumors and independent pathology reports. The optical photomicrographs will then be incorporated into the first specific aim as an iterative technique for identifying scattering sources and construction of more sensitive QUS models. PUBLIC HEALTH RELEVANCE: Up to 70% of the adult population has detectable thyroid nodules creating a crisis in the proper management of these nodules. High-frequency quantitative ultrasound can provide up to six independent parameters related to the tissue microstructure of thyroid nodules. The increased diagnostic information provided by high-frequency quantitative ultrasound will drastically improve the management crisis of thyroid nodules.