Clinical Translation of High Energy Phase-Sensitive X-ray Breast Tomosynthesis

 描述（由申请人提供）：该项目的目标是将相敏X射线断层合成技术转化为临床实践，以减少辐射剂量并提高乳腺癌诊断的准确性。该技术基于在120至150 kVp的高能量下工作的内联相敏X射线成像的原理。我们将建立一个病人成像系统，并进行临床前评估和第一阶段临床试验。 经过20多年的研究，数字乳腺断层合成摄影（DBT）最近获得了FDA的批准，并被引入临床实践。与投影乳腺X线摄影相比，DBT的主要优势在于其3D功能，可有效去除叠加的乳腺实质结构，提高乳腺癌的显著性和检测能力。然而，DBT有两个主要限制。第一个是关于其检测细微乳腺钙化的能力，第二个是与传统乳房X线摄影相比更高的辐射剂量。因此，有必要提高DBT的敏感性和特异性，降低患者的辐射剂量。已经表明，基于X射线相移的组织-病变对比度大于对应的衰减对比度。此外，虽然在常规的基于衰减的乳房成像中必须使用低X射线能量，但是在相敏成像中可以使用高X射线能量以减少辐射剂量。因此，我们建议将创新的相位敏感方法与DBT相结合。 我们建议的假设是，与当前的数字乳腺断层合成摄影（DBT）相比，高能相位敏感乳腺断层合成摄影（PBT）可以大大增强组织对比度并显著降低辐射剂量。为了验证我们的假设，我们将（1）组装一个高能量（2）优化相位恢复算法并在临床患者成像条件下进行测试;（3）表征患者成像系统及其关键部件的性能以进行系统优化，并将所提出的系统与DBT进行比较以确定辐射剂量节省;（4）对尸体和其他体模进行主观临床前评估，以确定患者研究的最佳操作参数;（5）对110名患者进行1期临床评估和统计分析，以比较相位敏感和传统断层合成系统。该研究将有助于将这种创新的相位敏感乳腺断层合成技术转化为临床实践，并提高乳腺成像的灵敏度和特异性。 癌症检测，同时也减少了辐射剂量。

 DESCRIPTION (provided by applicant): The objective of the project is to translate a phase-sensitive x-ray tomosynthesis technique to clinical practice to reduce radiation dose and improve accuracy in breast cancer diagnosis. The technique is based on the principle of inline phase-sensitive x-ray imaging operating at high energies of 120 to 150 kVp. We will build a patient imaging system and conduct preclinical evaluations and phase 1 clinical trial. As the result of more than 20 years of research, digital breast tomosynthesis (DBT) was recently approved by the FDA and introduced into clinical practice. The key advantage of DBT as compared with projection mammography is its 3D capability that effectively removes the superimposed breast parenchymal structures and improves the conspicuity and detection of breast cancer. However, there are two main limitations with DBT. The first regards its ability to detect subtle breast calcifications, and the second involves the higher radiation dose as compared with conventional mammography. It is therefore necessary to improve the sensitivity and specificity of DBT and reduce the radiation dose to patients. It has been shown that tissue- lesion contrast based on x-ray phase-shifts is greater than the corresponding attenuation contrast. In addition, while low x-ray energies must be used in conventional attenuation-based breast imaging, high x-ray energies can be used in phase-sensitive imaging to reduce the radiation dose. We therefore propose the integration of innovative phase-sensitive methods with DBT. The hypothesis of our proposal is that high energy phase-sensitive breast tomosynthesis (PBT) can greatly enhance tissue contrast and significantly reduce radiation dose as compared to current digital breast tomosynthesis (DBT). To test our hypotheses, we will (1) assemble a high energy (120-150 KV) x-ray phase- sensitive breast tomosynthesis system with a micro-focus tube source and a high-resolution flat panel detector; (2) optimize the phase retrieval algorithm and test it under clinical patient imaging conditions; (3) characterize the performance of the patient imaging system and its key components for system optimization, and compare the proposed system with DBT to determine radiation dose savings; (4) conduct subjective preclinical evaluations with cadaver and other phantoms to determine the optimal operating parameters for patient studies; (5) conduct a Phase 1 clinical evaluation and statistical analysis with 110 patients to compare phase- sensitive and conventional tomosynthesis systems. The proposed research will facilitate the translation of this innovative phase-sensitive breast tomosynthesis technique to clinical practice, and enhance the sensitivity and specificity of breast cancer detection while also reducing the radiation dose.