Multinuclear MRI to Monitor Breast Cancer Therapy

多核 MRI 监测乳腺癌治疗

• 批准号: 10581988
• 负责人: Ryan Brown
• 金额: $ 70.32万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581988
• 关键词: Address; Adjuvant Chemotherapy; Alternative Therapies; Anatomy; Bilateral; Biological Markers; Blood Vessels; Breast Cancer Model; Breast Cancer Patient; Breast Cancer therapy; Breast Magnetic Resonance Imaging; Breast-Conserving Surgery; Cancer Center; Carboplatin; Cell Death; Cell Survival; Cellularity; Chemotherapy-Oncologic Procedure; Clinical; Complement; Computer software; Consumption; Contralateral Breast; Custom; Cyclophosphamide; Data; Diffusion Magnetic Resonance Imaging; Disease; Doxorubicin; Drug Kinetics; Early identification; Early treatment; FDA approved; Fatty acid glycerol esters; Fingerprint; Gadolinium; Goals; Homeostasis; Image; In complete remission; Ions; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Mammography; Maps; Measures; Membrane; Metabolic; Methods; Modeling; Monitor; Neoadjuvant Therapy; Noise; Nuclear; Paclitaxel; Pathologic; Patient Care; Patient Monitoring; Patients; Perfusion; Permeability; Physiologic pulse; Prediction of Response to Therapy; Prognosis; Property; Protocols documentation; Protons; Scanning; Signal Transduction; Sodium; Standardization; Structure; System; Testing; Time; Tissues; Toxic effect; Treatment Protocols; Variant; Water; alternative treatment; breast imaging; cancer cell; cell injury; cohort; contrast enhanced; design; extracellular; imaging biomarker; imaging modality; improved; individualized medicine; insight; malignant breast neoplasm; novel; pembrolizumab; prognostic model; radio frequency; responders and non-responders; response; therapy outcome; treatment response; triple-negative invasive breast carcinoma; tumor; ultrasound

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.

项目摘要 新辅助化疗（NACT）是通过缩小局部晚期浸润性乳腺癌的范围来治疗的。 切除不能手术的肿瘤，并进行保乳手术。约30%的患者NACT不足 反应，但不能立即通过标准成像，如乳房X光检查，超声，或struc识别， 常规磁共振成像（MRI），因此受到不必要的毒性和阻碍， 定制治疗。仍然需要一种用于早期评估肿瘤对NACT反应的成像方法， 识别可能是替代疗法候选者的无应答者。我们的假设是，在回应过程中- 在某些情况下，由NACT诱导的癌细胞损伤可以通过改变细胞内的离子平衡来表征。 在pH、膜去极化和跨膜离子转运蛋白调节异常中。体内平衡的丧失 立即表现为细胞内钠浓度和细胞体积分数的变化，并且po- 细胞微环境本身。因此，我们建议实施一个新的定量多核 MRI（QMM）方案，其中来自质子（1H）MR指纹（MRF）的结构信息通过两种方法采集 CE（T1造影前/造影后）和动态CE（药代动力学）方法，以及钠代谢信息 （23 Na）MRF将在3 T的临床系统上同时采集。我们还将开发基于QMM的 成像生物标志物模型，其将与离子稳态相关的代谢度量与结构和 评估早期NACT期间癌细胞活力变化的药代动力学指标，作为治疗的预测指标 反应具体目标1：3 T乳腺成像的定量多核MRI（QMM）方案。(1.a)建立一个 1H/23 Na多通道RF线圈用于双侧乳腺MRI，3 T。(1.b)为了优化多核指纹（MNF）， 其由同时的1H/23 Na MRF采集组成。将采集MNF，2次超声心动图，以分离 使用狄克逊方法（狄克逊MNF）的水和脂肪信号，钆对比增强前后 (CE MNF），以及动态CE（DCE MNF）期间。(1.c)QMM协议的优化，包括 扩散张量成像（DTI）、CE MNF、DCE MNF和狄克逊MNF。具体目标2：纵向应用 NACT期间乳腺癌患者的QMM。(2)三阴性乳腺癌患者的纵向研究 接受标准临床NACT方案的癌症患者（TNBC），将扫描：（1）基线（pre-NACT）， (2)第1周期1周内，（3）第2周期1周内。具体目标3：开发生物标志物 根据QMM数据预测治疗效率的模型。(3.a)建立乳腺癌的影像学生物标志物模型 基于代谢、药代动力学和结构指标的组合， QMM协议。(3.b)为了确定来自模型的生物标志物的哪些组合是最佳预测因子， NACT后的病理反应。