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）用于通过收缩来治疗局部晚期侵入性乳腺癌 进行无法手术的肿瘤，并实现乳腺癌手术。大约30％的患者不足 反应，但没有立即通过标准成像来识别，例如乳房X线摄影，超声或结构 胞膜磁共振成像（MRI），因此受到不必要的毒性并挫败 定制治疗。仍需要一种早期评估肿瘤反应NACT的成像方法 确定可能是替代疗法的候选者的无反应者。我们的假设是，在做出回应时 nact诱导的癌细胞损害的特征是通过变化而导致离子体内平衡的损失 在pH中，跨膜离子转运蛋白的膜去极化和失调。失去体内平衡的丧失 立即表现为细胞内钠浓度和细胞体积分数的变化，以及 相应地，细胞微环境本身。因此，我们建议实施新的定量多核 MRI（QMM）协议，其中从质子（1H）MR指纹（MRF）中获得的结构信息都获得了 CE（T1前/后对比度）和动态CE（药代动力学）方法以及来自钠的代谢信息 （23NA）MRF将同时在3 t的临床系统上获得。我们还将开发基于QMM的 成像生物标志物模型将与离子稳态相关的代谢指标与结构和结构和 药代动力学指标以评估早期NACT期间癌细胞活力的变化作为治疗的预测指标 回复。特定目标1：用于乳房成像的定量多核MRI（QMM）方案3 t。（1.a）构建一个 1H/23NA多通道RF线圈在3 t时进行双侧乳房MRI。（1.B）优化多核指纹（MNF）， 由同时1H/23NA MRF收购组成。 MNF将以2个回声时间获得分开 使用Dixon方法（Dixon MNF）的水和脂肪信号，Gadolinium对比度增强之前和之后 （CE MNF），以及动态CE（DCE MNF）。 （1.C）优化QMM协议，其中包括 扩散张量成像（DTI），CE MNF，DCE MNF和DIXON MNF。特定目标2：纵向应用 NACT期间乳腺癌患者的QMM。 （2）对三重阴性乳房患者的纵向研究 接受标准临床NACT方案的癌症（TNBC），将被扫描：（1）基线（未进行）， （2）在第一周期的1周内，（3）在第二周期的1周内。特定目标3：开发生物标志物 QMM数据预后治疗效率的模型。 （3.a）开发乳房的成像生物标志物模型 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）确定模型的生物标志物的组合是最好的预测指标 NACT后的病理反应。