Active Contrast Encoding MRI for Breast Cancer

项目总结 尽管最近开发了各种新的治疗方法，但乳腺癌仍是第二大肿瘤。 导致女性癌症死亡的原因。抗血管生成药物联合常规细胞毒治疗 药物或免疫疗法是治疗侵袭性癌症的一种很有前途的方法。抗血管生成药物是 被认为是暂时使异常的血管系统正常化，并矛盾地增加血流量，因此 向肿瘤输送药物和效应器免疫细胞。然而，相当大一部分患者并不这样做。 对这种联合治疗的反应，目前尚不清楚失败是否由于抗血管生成药物的失败 使血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，它是 有必要同时评估血流和细胞死亡，以阐明机制和优化 联合治疗。在本提案中，我们调查了一次MRI采集和分析，该分析将允许 对两者的评估。 动态增强磁共振成像(DCE)作为大多数临床MRI的重要组成部分得到了广泛的应用 作为一种单一的MRI方法，它具有很高的潜力来估计两者的血流灌注 参数(如流量、F、血管体积分数、Vp和血管渗透率-表面积乘积PS) 和细胞参数(如间质体积分数，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，它测量 动态数据以及对比剂前的T1和B1对于血流灌注和细胞测量至关重要 参数。ACE-MRI还采用快速3D成像方法，以获得高空间和高分辨率 使用3D黄金角度超短回波时间(UTE)序列和图像的时间分辨率数据 一种结合压缩感知和并行成像的重建方法，也称为GRAP (黄金角径向稀疏度和平行度)。 在这项研究中，我们计划进一步发展血管紧张素转换酶核磁共振成像，以准确地估计造影剂的浓度。 使用直接采血方法(目标1)的血管血浆和组织，并评估τI的相关性 肿瘤代谢率和治疗反应与18F-FDG-PET和病理对照(目标2)。 总体而言，ACE-MRI参数将用于评估治疗反应和转移潜力(目标3)。 这项研究将在7T小型动物核磁共振扫描仪上用小鼠和人的乳腺癌模型进行。 然而，这项研究中开发的方法可以很容易地转化为临床应用，因为它用于 UTE序列在大多数临床扫描仪上都很容易获得。

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.