Metabolic Sodium MRI to Assess Early Response of Breast Cancer to Neoadjuvant Chemotherapy

代谢钠 MRI 评估乳腺癌对新辅助化疗的早期反应

• 批准号: 9386614
• 负责人: Ryan Brown
• 金额: $ 18.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386614
• 关键词: Abnormal Cell; Adriamycin PFS; Bilateral; Biochemical; Blood Vessels; Breast; Breast Cancer therapy; Breast-Conserving Surgery; Cancer Model; Cell Death; Cell Survival; Cell model; Cells; Cellularity; Computer software; Contrast Media; Cyclophosphamide; Data; Detection; Development; Diffusion Magnetic Resonance Imaging; Disease; Extracellular Fluid; Future; Goals; Homeostasis; Image; Inflammation; Intravenous; Ions; Lesion; Life; Magnetic Resonance Imaging; Magnetism; Maintenance; Malignant Neoplasms; Measurement; Measures; Membrane; Metabolic; Methodology; Methods; Modeling; Monitor; Neoadjuvant Therapy; Noise; Operative Surgical Procedures; Paclitaxel; Patient Care; Patients; Property; Protocols documentation; Protons; Pump; Reproducibility; Resolution; Safety; Savings; Scanning; Signal Transduction; Sodium; Sodium Chloride; Statistical Data Interpretation; Techniques; Time; Tissues; Variant; Water; advanced disease; base; breast imaging; cancer cell; cell injury; chemotherapy; clinical practice; computerized data processing; contrast enhanced; data acquisition; extracellular; image reconstruction; imaging biomarker; in vivo; insight; malignant breast neoplasm; metabolic imaging; musculoskeletal imaging; neuroimaging; novel; outcome prediction; prevent; programs; radiofrequency; response; sodium ion; treatment program; treatment response; triple-negative invasive breast carcinoma; tumor

Project Summary Neoadjuvant chemotherapy (NACT) is administered to treat invasive breast cancer before surgery. NACT offers the opportunity to evaluate tumor response to treatment in aggressive disease, and guide additional therapies for patients with inadequate response. Although methods such as dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and diffusion weighted imaging (DWI) can detect subsequent structural change in tumors (size, cellularity), insight on the tumor's metabolic response could inform patient care at an early stage in the treatment program. We propose to develop metabolic breast sodium (23Na) MRI to assess the metabolic response to NACT as soon as possible. Sodium MRI is based on the direct detection of endogenous sodium ions (Na+) in tissues, and allows a quantitative assessment of ion homeostasis, that is vital for cell viability. We propose to develop our technique at 7 T in order to generate 23Na images with adequate resolution to characterize small lesions common in breast cancer. Our hypothesis is that cell damage induced by NACT can be characterized by loss of ion homeostasis in the abnormal cells forming the malignant tumor, through dysregulation of their trans-membrane ion transporters, leading ultimately to cancer cell death and subsequent tumor shrinkage. As a consequence, large variations of Na+ concentrations inside the cancer cells are induced, which can be quantified with 23Na MRI. Measuring variations of both intracellular sodium concentration C1 (cell damage) and extracellular volume fraction 2 (cell death, inflammation) with 23Na MRI will give new metabolic information on the early effects of NACT, before tumor size reduction occurs. Our goal is to develop a 23Na MRI method to measure two new metabolic imaging biomarkers of loss of homeostasis (C1 and 2), and assess the efficacy of NACT in breast cancer as early as possible. Ultimately, the benefit for the patient would be the possibility of tailored breast cancer therapy. Specific aims are: AIM 1, Methodological development of metabolic 23Na MRI. (1.a) To build a dual-tuned multichannel radiofrequency coil (with 13 23Na-channels and 1 1H-channel per breast) that will allow bilateral breast 1H/23Na MRI at 7 T. (1.b) To optimize data acquisition and image reconstruction to generate 23Na images of the breast with 2.5-3 mm resolution in 7 min. We will perform DCE MRI for comparison. (1.c) To develop a software to quantify C1 and 2 based on 23Na MRI data and a model of cancer cells. A mechanistic model of loss of ion homeostasis due to NACT will also be developed in order to interpret the results. Reproducibility and repeatability will be assessed. AIM 2, Application of 23Na MRI to assess response of breast cancer to NACT. (2.a) To scan 12 patients with triple-negative breast cancer undergoing AC-T therapy (2 months of Adriamycin + Cyclophosphamide, then 3 months of Taxol): at baseline (pre-NACT); after the first AC cycle (2 weeks); after AC treatment (2 months); after complete NACT (5 months, pre-surgery). (2.b) To compare C1, 2, and tumor size at all 4 time-points. Using statistical analysis and the mechanistic model, we will assess which measurements are best predictors of the outcome at the end of AC treatment, and of NACT.

项目摘要 新辅助化疗（NACT）是在手术前用于治疗浸润性乳腺癌。NACT优惠 评估侵袭性疾病中肿瘤对治疗的反应并指导其他治疗的机会， 患者反应不足。虽然动态对比增强磁共振等方法 磁共振成像（DCE MRI）和弥散加权成像（DWI）可以检测肿瘤中随后的结构变化 (size，细胞结构），对肿瘤代谢反应的了解可以在肿瘤发生的早期阶段为患者护理提供信息。 治疗方案我们建议开发代谢性乳腺钠（23 Na）MRI，以评估代谢性 尽快回复NACT。钠MRI基于对内源性钠的直接检测 离子（Na+）在组织中，并允许定量评估离子稳态，这是至关重要的细胞活力。 我们建议在7 T下开发我们的技术，以便生成具有足够分辨率的23 Na图像， 描述乳腺癌常见的小病变。我们的假设是NACT诱导的细胞损伤 特征在于形成恶性肿瘤的异常细胞中离子稳态的丧失， 它们的跨膜离子转运蛋白的失调，最终导致癌细胞死亡和随后的 肿瘤缩小结果，诱导了癌细胞内Na+浓度的巨大变化， 可以用23 Na MRI定量艾德。测量细胞内钠浓度C1 (cell损伤）和细胞外体积分数2（细胞死亡，再灌注）与23 Na MRI将给出新的 在肿瘤尺寸减小发生之前，NACT的早期效应的代谢信息。我们的目标是开发 -23 Na MRI方法，用于测量体内平衡丧失的两种新的代谢成像生物标志物（C1和2），以及 尽早评估NACT在乳腺癌中的疗效。最终，患者的贝内将 乳腺癌治疗的可能性具体目标是：目标1， 代谢23 Na MRI。(1.a)建立一个双调谐多通道射频线圈（13个23 Na通道和1个 每个乳房1H通道），这将允许在7 T下进行双侧乳房1H/23 Na MRI。(1.b)为了优化数据采集， 图像重建，以在7分钟内生成分辨率为2.5-3 mm的23 Na乳腺图像。我们将执行 DCE MRI用于比较。(1.c)开发基于23 Na MRI数据和模型定量C1和C2的软件 癌细胞。还将开发由于NACT导致的离子稳态丧失的机理模型，以便 解释结果。将评估再现性和重复性。目的2，应用23 Na MRI评估 乳腺癌对NACT的反应。(2.a)扫描12例接受AC-T的三阴性乳腺癌患者 治疗（2个月阿霉素+环磷酰胺，然后3个月泰素）：基线时（NACT前）; 第一个AC周期（2周）; AC治疗后（2个月）;完成NACT后（5个月，术前）。（2.b） 比较所有4个时间点的C1、2和肿瘤大小。利用统计分析和机理模型，我们 将评估哪些测量值是AC治疗结束时结局和NACT的最佳预测因子。