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

 描述(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。这项技术是基于在线相敏X射线成像的原理，它工作在120到150kVp的高能下。我们将建立患者成像系统，进行临床前评估和一期临床试验。经过20多年的研究，数字乳腺断层合成术(DBT)最近被FDA批准并引入临床实践。与投影式钼靶摄影相比，DBT的主要优势是它的3D能力，可以有效地去除重叠的乳腺实质结构，提高乳腺癌的显着性和检测率。然而，DBT有两个主要限制。第一个是关于它检测微小的乳房钙化的能力，第二个是与传统的乳房X光检查相比，它涉及更高的辐射剂量。因此，有必要提高DBT的敏感性和特异性，减少对患者的辐射剂量。研究表明，基于X射线相移的组织损伤对比度大于相应的衰减对比度。此外，虽然在传统的基于衰减的乳房成像中必须使用低x射线能量，但在相敏成像中可以使用高x射线能量来减少辐射剂量。因此，我们建议将创新的相敏方法与DBT相结合。我们提出的假设是，与目前的数字乳腺断层合成(DBT)相比，高能相敏乳腺断层合成(PBT)可以显著增强组织对比度，显著降低辐射剂量。为了验证我们的假设，我们将(1)组装一个带有微聚焦管源和高分辨率平板探测器的高能(120-150 KV)X射线相敏乳腺断层扫描系统；(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，以优化系统，并与DBT进行比较，以确定辐射剂量节省；(4)使用身体和其他体模进行主观临床前评估，以确定用于患者研究的最佳操作参数；(5)对110例患者进行一期临床评估和统计分析，比较相敏和常规断层合成系统。建议的研究将有助于将这种创新的相敏乳房断层合成技术转化为临床应用，并提高乳房的敏感性和特异性。 在检测癌症的同时也降低了辐射剂量。

 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.