Integrated 3D Xray and Dynamic Tomographic Optical Breast Imaging System

描述(申请人提供)：不包括皮肤癌，乳腺癌仍然是影响女性人口的最常见的癌症，第二致命的癌症(仅次于肺癌)。根据美国癌症协会的数据，仅在2008年，就有超过18.2万名女性新诊断出这种疾病，近4.1万人死于这种疾病。虽然通过X光乳房X光检查的早期发现开始影响死亡率，但乳房X光检查在年轻女性和乳房致密的女性中仍然存在敏感度降低和显著的假阳性率问题。近年来，断层光学乳腺成像(TOBI)在提供组织功能信息以补充现有医学成像模式所提供的结构图像方面取得了可喜的进展。特别是，我们团队开发了一种光学/X射线断层合成设备，并在有限的临床试验中获得了有希望的初步结果，通过观察总血红蛋白对比来区分良恶性病变和正常组织。此外，我们观察到，乳房X光摄影压缩会导致乳腺组织光学特性的时间变化，并发现这些变化可用于计算组织耗氧量和血流量，以及携带关于不同组织区域生物力学特性的内在信息。受这些初步结果的鼓舞，我们建议，响应PAR-07-214，开发一种临床系统，该系统将高时间分辨率的TOBI与任何商业乳房X光照相或断层合成设备集成在一起，能够通过使用用于光学患者界面的X射线半透明材料来同时获取X射线和时间分辨率的光学图像。这种系统的开发将允许执行第一阶段临床试验，其中可以评估光学静态、动态和代谢标记物的诊断性能，以收集必要的统计信息，以计划第二阶段有效性试验。利用长期的合作关系，这项建议将领导光学技术和算法开发的Dr.Boas、拥有制造交钥匙光学成像系统丰富经验的定制工程公司TechEn Inc.以及数字乳房断层合成开发的先驱Dr.Kopans的临床团队聚集在一起。TechEn将与Boas博士的团队密切合作，构建动态光学成像系统的商业级原型，并与Kopans博士合作，在接受乳腺癌筛查和后续诊断的妇女身上进行临床测试，目标是微调临床操作程序和改进仪器，并收集关于光学组织参数诊断价值的初始数据，以及它们提高X射线断层成像的灵敏度和特异性的能力。与公共卫生相关：光学癌症标志物的开发可能会提高x射线乳房X光摄影的敏感性，导致早期癌症漏诊的情况减少；同时，特异性的提高可能会减少不必要的活检数量，从而降低患者的焦虑和医疗成本。 公共卫生相关性： 光学癌症标志物的开发可能会提高x射线乳房X光摄影的敏感性，导致早期癌症漏诊的减少；同时，特异性的提高可能会减少不必要的活检次数，从而降低患者的焦虑和医疗成本。

DESCRIPTION (provided by applicant): Excluding cancers of the skin, breast cancer remains the most common cancer affecting the female population, and the second most deadly (behind lung cancer). In 2008 alone, over 182,000 women will have been newly diagnosed and nearly 41,000 will have died of this disease according to the American Cancer Society. While early detection through X-ray mammographic screening is starting to impact mortality rates, mammography still suffers from reduced sensitivity in younger women and women with dense breasts and from a significant false positive rate. In recent years tomographic optical breast imaging (TOBI) has made promising advances in providing tissue functional information to complement the structural images offered by established medical imaging modalities. In particular, our group has developed a combined optical/x-ray tomosynthesis device and obtained promising initial results from a limited clinical trial, where total hemoglobin contrast was observed to discriminate between malignant and benign lesions and normal tissue. Additionally, we observed that mammographic compression induces temporal changes in breast tissue optical properties and discovered that these variations may be used to calculate tissue oxygen consumption and blood flow, as well as carrying intrinsic information about the biomechanical properties of various tissue regions. Encouraged by these initial results we propose, in response to PAR-07-214, to develop a clinical system that integrates high temporal resolution TOBI with any commercial mammography or tomosynthesis device with the ability to acquire simultaneous x-ray and time-resolved optical images by employing x-ray translucent materials for the optical patient interface. The development of such a system will allow the performance of Phase I clinical trials in which the diagnostic performance of optical static, dynamic and metabolic markers can be evaluated to gather the necessary statistical information to plan a Phase II effectiveness trial. Leveraging long standing relationships, this proposal brings together the team of Dr. Boas, leading optical technology and algorithm development, TechEn Inc., a custom engineering company with substantial experience building turn-key optical imaging systems, and the clinical group of Dr. Kopans, a pioneer in the development of digital breast tomosynthesis. TechEn, in close collaboration with Dr. Boas' group will construct a commercial grade prototype of the dynamic optical imaging system and in collaboration with Dr. Kopans the system will be clinically tested on women presenting for breast cancer screening as well as for follow-up diagnosis with the goal of fine tuning clinical operating procedure and refining the instrumentation, as well as gathering initial data on the diagnostic value of optical tissue parameters, and their ability to enhance the sensitivity and specificity of x-ray tomosynthesis. Public health relevance: development of optical cancer markers may improve sensitivity of x- ray mammography, leading to fewer missed early stage cancers; at the same time, improvements in specificity may decrease the number of un-necessary biopsies, thus reducing both patient anxiety and health care costs. PUBLIC HEALTH RELEVANCE: Development of optical cancer markers may improve sensitivity of x-ray mammography, leading to fewer missed early stage cancers; at the same time, improvements in specificity may decrease the number of un-necessary biopsies, thus reducing both patient anxiety and health care costs.