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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要新辅助化疗 (NACT) 用于在手术前治疗浸润性乳腺癌。有机会评估肿瘤对侵袭性疾病治疗的反应，并指导其他治疗尽管动态对比增强磁共振等方法反应不足。成像（DCE MRI）和弥散加权成像（DWI）可以检测肿瘤的后续结构变化（大小、细胞结构），对肿瘤代谢反应的了解可以为早期阶段的患者护理提供信息我们建议开发代谢性乳腺钠 (23Na) MRI 来评估代谢情况。尽快对 NACT 做出反应钠 MRI 是基于直接检测内源性钠。组织中的离子 (Na+)，并可以定量评估离子稳态，这对于细胞活力至关重要。我们建议在 7 T 下开发我们的技术，以生成具有足够分辨率的 23Na 图像我们的假设是 NACT 诱导细胞损伤。其特征在于形成恶性肿瘤的异常细胞中离子稳态的丧失，通过跨膜离子转运蛋白的失调，最终导致癌细胞死亡和随后的死亡结果，癌细胞内的 Na+ 浓度发生很大变化。可以通过 23Na MRI 测量细胞内钠浓度 C1 的变化来定量。（细胞损伤）和细胞外体积分数 2（细胞死亡、炎症）与 23Na MRI 将给出新的我们的目标是在肿瘤缩小之前开发有关 NACT 早期影响的代谢信息。 23Na MRI 方法可测量两种新的代谢成像生物标志物（C1 和 2），以及动态平衡丧失的情况尽早评估 NACT 对乳腺癌的疗效，最终会给患者带来好处。具体目标是：目标 1、方法学开发。代谢 23Na MRI (1.a) 构建双调谐多通道射频线圈（具有 13 个 23Na 通道和 1 个通道）每个乳房 1H 通道），这将允许在 7 T 下进行双侧乳房 1H/23Na MRI。 (1.b) 优化数据采集和我们将在 7 分钟内执行图像重建，生成分辨率为 2.5-3 毫米的 23Na 乳房图像。用于比较的 DCE MRI (1.c) 开发基于 23Na MRI 数据和模型量化 C1 和 2 的软件。还将开发由于 NACT 导致的离子稳态丧失的机制模型。将评估结果的再现性和重复性。 AIM 2，应用 23Na MRI 进行评估。乳腺癌对 NACT 的反应 (2.a) 对 12 名接受 AC-T 的三阴性乳腺癌患者进行扫描。治疗（2 个月的阿霉素 + 环磷酰胺，然后 3 个月的紫杉醇）：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，手术前）(2.b)。为了比较所有 4 个时间点的 C1、2 和肿瘤大小，我们使用统计分析和机制模型。将评估哪些测量结果是 AC 治疗和 NACT 结束时结果的最佳预测因素。