Simultaneous Emission and Transmission Mammotomography

描述（由申请人提供）：本提案的总体目标是开发用于专用乳房和腋窝成像的双模单光子发射计算机断层扫描（SPECT）和x射线计算机乳房断层扫描（CmT）扫描仪，并将该系统纳入常规乳腺诊断保健。我们是第一个构思、实施并开始临床评估这种双模态分子乳房成像装置的团队。在该项目的前5年期间，开发了三种专用的人类乳房成像设备，并充分表征：SPECT， CmT和集成两者的混合设备。成像性能超出了最初的具体目标的预期和目标。对于SPECT子系统，我们将高性能半导体探测器集成在能够任意，全三维（3D）轨迹的新型龙门上。我们成像较小的病变与较低的模拟生物吸收比已经成像的其他人。对于CmT子系统，我们开发了一种创新的、鲁棒的准单色x射线锥束，可以在均匀取样的乳房体积内提供各向同性分辨率的3D解剖图像。我们已经显示，与二维数字x线乳房x线摄影相比，在统计学上显著提高了乳房幻象中小的、低对比度病变的观察者可检出性。重要的是，该CmT系统在总吸收剂量低于双视图筛查乳房x光检查的情况下获得了这些结果。该集成混合系统已经通过幻影成像研究进行了彻底的表征，成功地用于女性乳腺癌的成像，并产生了高质量的3D配准和融合图像。这项为期4年的延续提案包括将我们现有的混合成像设备纳入正在进行的NIH资助的热疗乳房治疗临床试验。该试验将评估40名人类受试者的半定量三维放射性药物负载脂质体生物分布。使用专门为该提案开发的窄边数字平板探测器，以及允许实时散射校正测量的紧凑x射线源过滤组合，将开发一个全新的CmT子系统，提供增强的前胸壁成像。这种新的几何优化和患者友好的系统将是第一个混合成像技术，允许全乳房和腋窝淋巴结的各向同性均匀成像。这两个子系统都将为我们的广义迭代重建代码提供全3d高分辨率数据，该代码将包含运动、散射和衰减校正。新系统将被表征和校准，以提供绝对信号量化到已知值的5%以内。这种新的混合型乳房x线摄影系统将在20名局部晚期乳腺癌患者中进行评估，以便通过改进的BIRADS词典确定图像参数的方差，并确定2期临床试验的统计能力。鉴于我们目前的积极进展和结果，我们认为我们的新的混合SPECT-CmT系统很可能被证明是一种有价值的临床工具。公共卫生相关性：本研究计划的总体目标是开发和评估专用的三维（3D）乳房成像，称为“乳房断层扫描”，同时能够使用SPECT进行功能发射成像，并使用CT进行垂坠、未压缩乳房和相关腋窝区域的解剖透射成像。在第一个5年期间取得了重大进展，这一修订后的建议提出了一种改变范例的方法，用于专门的乳房成像，预计将导致更好的临床解释和量化来自综合成像模式的信息，并最终导致更好的诊断和监测乳腺癌，这对乳腺癌的公共和个人健康问题非常重要。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a dual-modality single photon emission computed tomography (SPECT) and x-ray computed mammotomography (CmT) scanner for dedicated breast and axillary imaging, and to incorporate this system into routine diagnostic breast healthcare. We are the first group to conceive, implement, and begin to clinically evaluate such a dual-modality molecular breast imaging device. In the first 5- year period of this project, three dedicated human breast imaging devices were developed and fully characterized: SPECT, CmT and a hybrid device integrating the two. The imaging performances exceeded the expectations and goals of the original Specific Aims. For the SPECT subsystem, we integrated a high- performance semiconductor detector on a novel gantry capable of arbitrary, fully 3-dimensional (3D) trajectories. We imaged smaller lesions with lower simulated biological uptake than has been imaged by others. For the CmT subsystem, we developed an innovative and robust quasi-monochromatic x-ray cone beam that can provide 3D anatomical images with isotropic resolution throughout a uniformly sampled breast volume. We have shown statistically significantly improved observer detectability of small, low contrast lesions in breast phantoms compared with 2D digital x-ray mammography. Importantly, this CmT system helped yield these results with total absorbed dose below that of dual-view screening mammography. The integrated hybrid system has been thoroughly characterized with phantom imaging studies, successfully used in imaging women with breast cancer, and yielded high quality 3D registered and fused images. This 4-year continuation proposal includes incorporation of our existing hybrid imaging device into an ongoing NIH funded hyperthermia breast therapeutics clinical trial. This trial will evaluate the semiquantitative 3D radiopharmaceutical-loaded liposome biodistributions in 40 human subjects. Using a narrow edge digital flat-panel detector developed specifically for this proposal, along with a compact x-ray source-filtration combination allowing real-time scatter correction measurements, a totally new CmT subsystem will be developed, providing enhanced anterior chest wall imaging. This new geometrically optimal and patient friendly system will be the first hybrid imaging technology to allow isotropically uniform imaging of the full breast and axillary nodes. Both subsystems will provide fully-3D high resolution data for our generalized iterative reconstruction code that will incorporate motion, scatter and attenuation corrections. The new system will be characterized and calibrated to provide absolute signal quantification to within 5% of known values. This new hybrid mammotomography system will be evaluated in 20 locally advanced breast cancer patients, so that the variance of image parameters can be determined with a modified BIRADS lexicon, and statistical power can be determined for a Phase 2 clinical trial. Given our positive developments and results thus far, we think it is likely that our new hybrid SPECT-CmT system will prove to be a valuable clinical tool. PUBLIC HEALTH RELEVANCE: The overall goal of this research proposal is to develop and evaluate dedicated three-dimensional (3D) breast imaging, termed "mammotomography," simultaneously capable of functional-emission imaging with SPECT and anatomical-transmission imaging with CT of a pendant, uncompressed breast and associated axillary regions. Significant strides were made in the first 5-year period, and this revised proposal presents a paradigm changing approach to dedicated breast imaging that is expected to result in better clinical interpretation and quantification of information from the combined imaging modalities, and ultimately lead to better diagnosis for and monitoring of breast cancer, which is of great importance in the public and personal health problem of breast cancer.