Multinuclear MRI to Monitor Breast Cancer Therapy

项目摘要 采用新辅助化疗(NACT)治疗局部晚期浸润性乳腺癌。 治疗无法手术的肿瘤，并使保乳手术成为可能。约30%的患者NACT不足 有反应，但不能立即通过标准成像，如乳房X光检查，超声波，或结构- 文化磁共振成像(MRI)，因此受到不必要的毒性和阻碍 定制化治疗。仍然需要一种早期评估肿瘤对NACT反应的成像方法。 确定无反应者可能是替代疗法的候选者。我们的假设是，在回应PA时- NACT引起的癌细胞损伤的特征是通过改变细胞内离子的动态平衡。 在pH条件下，膜去极化和跨膜离子转运体调节失调。这种动态平衡的丧失 立即表现为细胞内钠浓度和细胞体积分数的变化，并 也就是细胞微环境本身。因此，我们建议实施一种新的量化多核 MRI(QMM)协议，其中来自质子(1H)MR指纹(MRF)的结构信息 CE(T1前后对比)和动态CE(药代动力学)方法，以及来自钠的代谢信息 (23Na)MRF将在3T的临床系统上同时获得。我们还将开发基于QMM的 结合与离子动态平衡相关的代谢指标和结构和 评价早期癌细胞活力变化的药代动力学指标作为治疗的预测指标 回应。具体目标1：定量多核磁共振成像(QMM)方案用于乳腺3T(1.A)成像 1H/23Na多通道射频线圈用于3T的双侧乳腺MRI(1.b)优化多核指纹(MNF)， 它包括同时采集1H/23Na磁流变液。MNF将以2个回声时间进行分离 使用Dixon方法(Dixon MNF)的水和脂肪信号，在Gd增强前后 (CE MNF)，以及动态CE(DCE MNF)。(1.c)QMM协议优化，包括 弥散张量成像(DTI)、磁共振弥散张量成像(CEMNF)、弥散张量成像(DCEMNF)和Dixon MNF。具体目标2：纵向应用 乳腺癌患者在NACT期间的QMM。(2)三重阴性乳腺患者的纵向研究 接受标准临床NACT方案的癌症(TNBC)，将接受以下扫描：(1)基线(NACT前)， (2)第1周期后1周内；(3)第2周期后1周内。具体目标3：开发生物标记物 基于QMM数据的疗效预测模型。(3.a)建立乳腺影像生物标志物模型 癌症对治疗的反应基于代谢、药代动力学和结构指标的组合 QMM协议。(3.b)确定模型中的哪些生物标志物组合是最好的预测因子 NACT后病理反应。

Project Summary Neoadjuvant chemotherapy (NACT) is administered to treat locally advanced invasive breast cancer by shrink- ing inoperable tumors, and to enable breast-conserving surgery. About 30% of patients have inadequate NACT response, but are not immediately identified by standard imaging such as mammography, ultrasound, or struc- tural magnetic resonance imaging (MRI), and are therefore subjected to unnecessary toxicity and thwarted from customized treatment. An imaging method for early assessment of tumor response to NACT is still needed to identify non-responders that may be candidates for alternative therapy. Our hypothesis is that, in responding pa- tients, cancer cell damage induced by NACT can be characterized by loss of ion homeostasis through changes in pH, membrane depolarization and dysregulation of transmembrane ion transporters. This loss of homeostasis immediately manifests as variations in the intracellular sodium concentration and cellular volume fraction, and po- tentially the cellular microenvironment itself. We therefore propose to implement a new quantitative multinuclear MRI (QMM) protocol, where structural information from proton (1H) MR fingerprinting (MRF) acquired with both CE (T1 pre/post contrast) and dynamic CE (pharmacokinetics) methods, and metabolic information from sodium (23Na) MRF will be acquired simultaneously on a clinical system at 3 T. We will also develop a QMM-based imaging biomarker model that combines the metabolic metrics related to ion homeostasis with the structural and pharmacokinetic metrics to assess changes in cancer cell viability during early NACT as a predictor of therapy response. Specific aim 1: Quantitative multinuclear MRI (QMM) protocol for breast imaging at 3 T. (1.a) To build a 1H/23Na multichannel RF coil for bilateral breast MRI at 3 T. (1.b) To optimize a multinuclear fingerprinting (MNF), which consists of a simultaneous 1H/23Na MRF acquisition. MNF will be acquired with 2 echo times to separate water and fat signals using the Dixon method (Dixon MNF), before and after Gadolinium contrast enhancement (CE MNF), and also during dynamic CE (DCE MNF). (1.c) Optimization of the QMM protocol, which includes diffusion tensor imaging (DTI), CE MNF, DCE MNF, and Dixon MNF. Specific aim 2: Longitudinal application of QMM in patients with breast cancer during NACT. (2) Longitudinal study in patients with triple negative breast cancer (TNBC) that undergo standard clinical NACT regimen, who will be scanned: (1) baseline (pre-NACT), (2) within 1 week of the 1st cycle, (3) within 1 week of the 2nd cycle. Specific aim 3: To develop biomarker model for prognosis of therapy efficiency from QMM data. (3.a) To develop an imaging biomarker model of breast cancer response to therapy based on the combination of metabolic, pharmacokinetic, and structural metrics from the QMM protocol. (3.b) To determine which combinations of biomarkers from the model are best predictor of pathological response after NACT.