Simultaneous Emission and Transmission Mammotomography

描述(申请人提供)：这项提案的总体目标是开发一种用于专用乳房和腋窝成像的双模式单光子发射计算机断层扫描(SPECT)和X射线计算机乳腺断层扫描(CMT)扫描仪，并将该系统整合到常规诊断性乳房保健中。我们是第一个构思、实施并开始临床评估这种双模式分子乳腺成像设备的小组。在该项目的前五年期间，开发了三种专用的人类乳房成像设备，并对其进行了充分的表征：SPECT、CMT和一种集成了两者的混合设备。成像性能超出了原特定目标的预期和目标。对于SPECT子系统，我们在一个新的门架上集成了一个高性能的半导体探测器，能够进行任意的全三维(3D)轨迹。我们成像了较小的病变，但模拟生物摄取率比其他成像要低。对于CMT子系统，我们开发了一种创新且坚固的准单色X射线锥束，它可以在整个均匀采样的乳腺体积内提供各向同性分辨率的3D解剖图像。与2D数字X光摄影相比，我们已经显示出在统计上显著提高了观察者对乳房模体中小的、低对比度病变的可探测性。重要的是，这种CMT系统有助于在总吸收剂量低于双视角筛查乳房X光检查的情况下获得这些结果。集成的混合系统已经通过体模成像研究得到了彻底的特征，并成功地用于乳腺癌女性患者的成像，并产生了高质量的3D配准和融合图像。这份为期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。这项试验将评估半定量3D放射性药物载脂体脂质体在40名受试者中的生物分布。使用专门为这项提议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型X射线源过滤组合，将开发一种全新的CMT子系统，提供增强的前胸壁成像。这一新的几何优化和患者友好的系统将是第一个允许对整个乳房和腋窝结节进行各向同性均匀成像的混合成像技术。这两个子系统都将为我们的通用迭代重建代码提供全3D高分辨率数据，该代码将包括运动、散射和衰减校正。新系统的特性和校准将提供绝对信号量化到已知数值的5%以内。这一新的混合乳房X光扫描系统将在20名局部晚期乳腺癌患者中进行评估，以便可以使用改进的BIRADS词典来确定图像参数的方差，并可以确定第二阶段临床试验的统计能力。鉴于我们到目前为止的积极发展和结果，我们认为我们的新的SPECT-CMT混合系统很可能被证明是一种有价值的临床工具。与公共健康相关：这项研究提案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X光断层扫描”，同时能够通过SPECT进行功能发射成像，并通过CT对悬垂、未受压的乳房和相关腋窝区域进行解剖传输成像。在头五年期间取得了重大进展，这项修订提案提出了一种改变专用乳房成像的范式的方法，预计将导致更好的临床解释和来自综合成像模式的信息的量化，并最终导致更好的乳腺癌诊断和监测，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.