Validation and Standardization of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker in Breast Cancer

摘要 乳腺癌非常常见，每8名美国妇女中就有1人患上乳腺癌，是第二大病因 通过筛查早期发现是改善癌症死亡率的根本途径。 生存乳房X光检查显示乳腺致密的女性患乳腺癌的风险增加 乳腺密度的增加降低了乳腺X线摄影检测癌症的灵敏度。因此，在本发明中， 越来越多的州通过立法，要求医疗服务提供者告知妇女， 增加了，增加了额外的筛选。动态增强MRI（DCE-MRI）是最常见的 这是一种检测乳腺癌的敏感技术，特别是在乳房致密的女性中。然而，重叠在 乳腺良性和恶性病变在DCE-MRI上的表现会产生许多假阳性， 为了减少不必要的活检次数， 这将导致扩大使用这种高度敏感的筛选工具。此外，高成本和安全性 对钆基造影剂的关注限制了许多妇女进行乳房MRI筛查的可及性， 因此，识别用于检测乳腺癌的非造影剂替代物将具有很强的临床影响。 一种有前途的辅助MRI技术是弥散加权成像（DWI），它间接评估组织 显微结构，并可以提供补充信息，DCE-MRI病变表征。我们有 先前证实良性肿瘤与良性肿瘤之间的表观扩散系数（ADC）值存在显著差异， ADC测量可提高常规乳腺癌的阳性预测值， 核磁共振我们最近在一项多中心试验（ACRIN 6702）中证实了这些发现。我们还注意到， 在不使用造影剂的情况下，乳腺摄影和临床隐匿性癌症在DWI上可见，这表明 DWI可以提供比DCE-MRI更快、更便宜、更安全的筛查选择，这是当前的主题 在父母资助（NIH R 01-CA 207290）中进行了探索。 拟议研究的目的是使克服障碍的技术方法标准化并加以验证 将ADC作为诊断生物标志物转化为临床实践。已知地址的图像更正 将实现与梯度非线性、配准不良和几何失真相关的不准确性，以及 将优化测量病变ADC的方法，以最大限度地提高诊断性能和可靠性。的 将使用现有的ACRIN 6702多中心数据集对试验进行完善，以确保广泛的普遍性， 在几个地点进行了前瞻性测试。如果成功，标准化ADC测定可更准确地评估 在检测时恶性肿瘤的概率将减少不必要的（良性）活检的数量 作为乳腺MRI筛查的结果，使用或不使用造影剂。

Abstract Breast cancer is extremely common, striking 1 in 8 American women, and is the second leading cause of cancer death among women in the U.S. Earlier detection through screening is a fundamental way to improve survival. Women with dense breasts on screening mammography have increased risk of developing breast cancer, and increased breast density reduces the sensitivity of mammography for cancer detection. As a result, a growing number of states have passed legislation mandating that providers inform women if their breast density is increased, warranting supplemental screening. Dynamic contrast enhanced MRI (DCE-MRI) is the most sensitive technique for detecting breast cancer, particularly in women with dense breasts. However, overlap in the appearance of benign and malignant breast lesions on DCE-MRI can produce many false positives, and there is a clear need to improve the specificity of breast MRI in order to limit the number of unnecessary biopsies that will result from expanded use of this highly sensitive screening tool. Furthermore, the high costs and safety concerns of gadolinium-based contrast agents limit the accessibility of breast MRI screening for many women, so identifying a non-contrast alternative for detecting breast cancer would have strong clinical impact. A promising adjunct MRI technique is diffusion-weighted imaging (DWI), which indirectly assesses tissue microstructure and can provide complementary information to DCE-MRI for lesion characterization. We have previously demonstrated significant differences in apparent diffusion coefficient (ADC) values between benign and malignant lesions and that ADC measures can increase the positive predictive value of conventional breast MRI. We recently confirmed these findings in a multicenter trial (ACRIN 6702). We have also observed that many mammographically and clinically-occult cancers are visible on DWI without using a contrast agent, suggesting DWI could provide a faster, less expensive, and safer screening option than DCE-MRI, which is the topic being explored in the parent grant (NIH R01-CA207290). Aims of the proposed study will be to standardize and validate technical approaches to overcome hurdles in translating ADC as diagnostic biomarker into clinical practice. Image corrections to address known inaccuracies related to gradient nonlinearities, misregistration and geometric distortion will be implemented, and methodology for measuring lesion ADC will be optimized to maximize diagnostic performance and reliability. The assay will be refined using the existing ACRIN 6702 multicenter dataset to ensure wide generalizability and tested prospectively at several sites. If successful, a standardized ADC assay to more accurately assess the probability of malignancy at the time of detection would reduce the number of unnecessary (benign) biopsies performed as a result of breast MRI screening, with or without contrast.