Virtual Clinical Trials: Simulation of Digital Breast Tomosynthesis Screening

描述(由申请人提供)：虽然乳房X光检查显示可以降低乳腺癌死亡率，但其敏感度和特异度并不理想。这导致了新的乳房筛查技术的发展，如数字乳房断层合成(DBT)和专用乳房CT。这些新技术在早期研究中显示出了希望，但它们固有的复杂性对优化提出了挑战。乳房成像代表了一个复杂的图像采集、显示和解释链，最好在临床试验中进行测试。进行临床试验比较DBT系统的所有可能配置是不切实际的。作为回应，我们提出了一种创新的系统来执行乳房成像技术的虚拟临床试验(VCT)。我们设想VCT将成为临床试验的补充，并在成像设备的临床前测试中发挥关键作用，从而使人类临床试验可以针对最有希望的设备和适当的临床角色。这种方法利用了合作者的独特专业知识。宾夕法尼亚大学开发了一种3D虚拟乳房模型，非常适合用于VCT；它提供了无限的解剖变化，可以模拟多种乳房病变。Barco Mevic(医学虚拟成像链)是可用的最复杂的观察者建模工具之一，集成了图像采集、图像处理、图像重建、图像显示以及人类视觉和感知系统。我们建议将这些技术集成到用于数字乳房X光摄影(DM)和DBT的VCT系统中。VCT系统将用于模拟ACRIN临床试验网络正在进行的DBT和DM的实际试验，以便将灵敏度和特异度方面的相对性能与实际临床试验进行比较。VCT组件的丰富性将允许对乳腺实质、病变和观察者表现进行尽可能广泛的采样。我们提出以下建议。现有的体素体模和病变模型将得到改进。图像仿真环境将适用于对HOLOGIC DM/DBT系统进行建模。通过研究并实现人类时空对比度灵敏度函数，将现有的二维信道化霍特林观测器(CHO)应用于3D(2D时间)。将测试各种通道机制，并将包括感知因素，如记忆随时间退化。2D和3D 2-AFC实验将与人类观察者一起进行，以评估每个观察者、形态和病变类型的观察者表现。Mevic观测器模型的性能将用真实和合成的DM和DBT图像进行测试。所得到的经验证的2D和3D观察者模型将用于进行DBT和DM筛查的VCT。VCT的结果将与正在进行的DBT和DM筛查的ACRIN PA临床试验的结果进行比较。如果成功，VCT系统可以用来测试乳腺癌筛查技术的技术变化，以更具成本效益的方式加快改进成像系统的开发和临床实施。 与公共健康相关：医学成像在新设备和新方法方面都在经历快速扩张；随着医疗设备开发步伐的加快，人们面临着加快临床试验速度或寻找一些临床试验的有效和安全替代方案的两难境地。作为回应，我们建议开发一种创新的系统来执行乳腺癌筛查技术的虚拟临床试验(VCT)，该系统建立在我们之前开发虚拟乳房体模和用于3D乳房成像的复杂观察者模型的基础上。如果成功，VCT系统可以用来测试乳腺癌筛查技术的技术变化，以更具成本效益的方式加快改进成像系统的开发和临床实施。

DESCRIPTION (provided by applicant): Although shown to decrease breast cancer mortality, mammographic screening suffers from less than optimal sensitivity and specificity. This has led to the development of new breast screening technologies such as digital breast tomosynthesis (DBT) and dedicated breast CT. These new technologies have shown promise in early studies, but their innate complexity challenges optimization. Breast imaging represents a complex chain of image acquisition, display and interpretation that is best tested in a clinical trial. Conducting clinical trials comparing all potential configurations of DBT systems is simply not practical. In response, we propose an innovative system to perform virtual clinical trials (VCT) of breast imaging technologies. We envision VCTs being complementary to clinical trials, and having a critical role in preclinical testing of imaging devices, so that human clinical trials may be targeted to the most promising devices and appropriate clinical roles. This approach leverages unique expertise of the collaborators. The University of Pennsylvania has developed a 3D virtual breast phantom that is well suited for use in VCTs; it provides infinite anatomic variation and can simulate a multitude of breast lesions. The Barco MeVIC (Medical Virtual Imaging Chain) is among the most sophisticated observer modeling tools available, incorporating image acquisition, image processing, image reconstruction, image display, and the human visual and perceptual systems. We propose to integrate these technologies into a VCT system for digital mammography (DM) and DBT. The VCT system will be used to simulate an actual trial of DBT and DM being conducted by the ACRIN clinical trials network in order to compare relative performance in terms of sensitivity and specificity with an actual clinical trial. The richness of the VCT components will allow exploration of the broadest possible sampling of breast parenchyma, lesions, and observer performance. We propose the following. The existing voxel phantom and lesion models will be refined. The image simulation environment will be adapted to model the Hologic DM/DBT system. The existing MeVIC 2D channelized Hotelling observer (CHO) will be adapted to 3D (2D + time) by studying and then implementing the human spatio-temporal contrast sensitivity function. Various channeling mechanisms will be tested and perceptual factors such as degradation of memory with time will be included. 2D and 3D 2-AFC experiments will be conducted with human observers to estimate observer performance for each observer, modality and lesion type. The performance of the MeVIC observer models will be tested with real and synthetic DM and DBT images. The resultant validated 2D and 3D observer models will be used to conduct a VCT of DBT and DM screening. The results of the VCT will be compared to the results of the ongoing ACRIN PA clinical trial of DBT and DM screening. If successful, the VCT system can be utilized to test technology variations in breast cancer screening technology, accelerating development and clinical implementation of improved imaging systems in a more cost-efficient fashion. PUBLIC HEALTH RELEVANCE: Medical imaging is undergoing a rapid expansion both in terms of new devices and new methodologies; as the pace of medical device development increases, one is faced with the quandary of increasing the pace of clinical trials or finding effective and safe alternatives to some clinical trials. In response, we propose the development of an innovative system to perform virtual clinical trials (VCT) of breast cancer screening technology that builds on our prior work in developing a virtual breast phantom and complex observer model for 3D breast imaging. If successful, the VCT system can be utilized to test technology variations in breast cancer screening technology, accelerating development and clinical implementation of improved imaging systems in a more cost-efficient fashion.