Active Contrast Encoding MRI for Breast Cancer

项目摘要 尽管最近开发了各种新的治疗方法，但乳腺癌仍然是第二大癌症。 女性癌症死亡的原因。抗血管生成药物联合常规细胞毒性药物治疗 药物或免疫疗法是治疗侵袭性癌症的有希望的手段。抗血管生成药物 被认为是暂时正常化异常的脉管系统，并矛盾地增加血流量， 将药物和效应免疫细胞递送至肿瘤。然而，有相当一部分患者没有 对这种联合治疗有反应，目前还不清楚失败是否是由于抗血管生成药物的失败。 以使脉管系统正常化或细胞毒性药物或免疫细胞不能杀死癌细胞。因此 必须评估血流和细胞死亡，以阐明机制并优化 联合治疗。在本提案中，我们研究了单个MRI采集和分析， 两者的评价。 动态对比增强MRI（Dynamic Contrast Enhancement MRI，DCE）作为临床MRI的重要组成部分，已得到广泛应用 检查用于诊断癌症，并且它作为单一MRI方法具有很高的潜力，可以估计灌注 参数（如流量F、血管容积分数vp和血管通透性-表面积乘积PS） 和细胞参数（例如，间隙体积分数ve和细胞内水寿命τi）。最近， 我们开发了一种新的数据采集方法，即主动对比度编码（ACE）-MRI， 动态数据以及造影前T1和B1，这对于测量灌注和细胞 参数ACE-MRI还采用快速3D成像方法来实现，以获取高空间和高分辨率图像。 使用3D黄金角超短回波时间（UTE）序列和图像的时间分辨率数据 一种将压缩感知和并行成像结合起来的联合收割机重建方法，也称为GRASP （黄金角放射稀疏和平行）。 在这项研究中，我们计划进一步开发ACE-MRI，以准确估计造影剂浓度， 血管血浆和组织使用直接采血法（目的1），并评估τi的相关性 肿瘤代谢率和治疗反应与18F-FDG-PET和病理学比较（目的2）。 总体而言，ACE-MRI参数将用于评估治疗缓解和转移潜力（目的3）。 本研究将在7 T小动物MRI扫描仪上使用鼠和人乳腺癌模型进行。 然而，在这项研究中开发的方法可以很容易地转化为临床应用，因为它是在一个 UTE序列在大多数临床扫描仪上可用。

PROJECT SUMMARY Despite recent development of various new approaches to therapy, breast cancer remains the second leading cause of cancer death in women. Treatment with anti-angiogenic drugs combined with conventional cytotoxic drugs or immunotherapy is a promising means of treating aggressive cancer. Anti-angiogenic drugs are thought to temporarily normalize abnormal vasculature and paradoxically increase blood flow and hence delivery of drug and effector immune cells to tumors. However, a substantial proportion of patients do not respond to this combination therapy and it is unclear whether the failure is due to failure of the anti-angiogenic to normalize the vasculature or failure of the cytotoxic drugs or immune cells to kill cancer cells. It is therefore necessary to assess both blood flow and cell death to elucidate the mechanism and to optimize the combination treatments. In this proposal we investigate a single MRI acquisition and analysis that will allow assessment of both. Dynamic contrast enhanced (DCE) MRI has been widely used as an important part of most clinical MRI exams for diagnosis of cancer, and it holds high potential as a single MRI method to estimate both perfusion parameters (such as, flow, F, vascular volume fraction, vp, and vascular permeability-surface area product, PS) and cellular parameters (such as, interstitial volume fraction, ve, and intracellular water life time, τi). Recently, we developed a novel data acquisition method, namely active contrast encoding (ACE)-MRI, which measures dynamic data together with pre-contrast T1 and B1 that are critical for measurement of perfusion and cellular parameters. ACE-MRI is also implemented with a fast 3D imaging method to acquire high-spatial and high- temporal resolution data using a 3D golden-angle ultra-short echo-time (UTE) sequence and an image reconstruction method to combine both compressed sensing and parallel imaging, also known as GRASP (Golden-angle RAdial Sparsity and Parallel). In this study, we plan to further develop ACE-MRI for accurate estimation of contrast agent concentration in vascular plasma and tissue using a direct blood sampling method (Aim 1), and to assess the association of τi with tumor metabolic rate and treatment response in comparison with 18F-FDG-PET and pathology (Aim 2). Overall, the ACE-MRI parameters will be used to assess treatment response and metastatic potential (Aim 3). This study will be conducted with murine and human breast cancer models at a 7T small animal MRI scanner. However, the methods developed in this study can be easily translated to clinical applications as it is used on a UTE sequence readily available on most clinical scanners.