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.

项目摘要新辅助化学疗法（NACT）是在手术前治疗浸润性乳腺癌的。 NACT提供评估肿瘤对侵略性疾病治疗的反应的机会，并指导其他疗法反应不足的患者。尽管诸如动态对比增强磁共振之类的方法成像（DCE MRI）和扩散加权成像（DWI）可以检测肿瘤的随后结构变化（大小，细胞），对肿瘤的代谢反应的见解可以在早期阶段为患者护理提供信息治疗计划。我们建议开发代谢乳腺钠（23NA）MRI来评估代谢对NACT的反应尽快。 MRI钠基于内源钠的直接检测组织中的离子（Na+），并允许对离子稳态的定量评估，这对于细胞活力至关重要。我们建议以7 t开发我们的技术表征乳腺癌常见的小病变。我们的假设是NACT诱导的细胞损伤可以通过其运输膜离子转运蛋白的失调，最终导致癌细胞死亡，随后导致肿瘤收缩。结果，诱导癌细胞内Na+浓度的巨大变化，可以用23NA MRI量化。测量两种细胞内钠浓度C1的变化（细胞损伤）和细胞外体积分数2（细胞死亡，炎症）用23NA MRI提供新的在减少肿瘤大小之前，有关NACT早期作用的代谢信息。我们的目标是发展一种23NA MRI方法，用于测量稳态丧失的两种新代谢成像生物标志物（C1和2），以及尽早评估NACT在乳腺癌中的效率。最终，对患者的好处将是量身定制的乳腺癌治疗的可能性。特定目的是：目标1，方法论发展代谢23NA MRI。（1.a）建造双音调的多通道射频线圈（带有13个23NA通道和1个每乳房的1h通道），将允许双侧乳房1H/23NA MRI在7 T.（1.B）以优化数据获取和图像重建以在7分钟内产生2.5-3 mm分辨率的乳房的23NA图像。我们将表演 DCE MRI进行比较。（1.c）基于23NA MRI数据和模型开发软件来量化C1和2 癌细胞。还将开发出一个因NACT引起的离子稳态丧失的机械模型，以便为了解释结果。可重复性和可重复性将被评估。 AIM 2，应用23NA 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个月的阿霉素 +环磷酰胺，然后为3个月的紫杉醇）：基线时（无效）；后第一个AC周期（2周）；交流治疗后（2个月）；完成裸露后（5个月，手术前）。（2.b）比较所有4个时间点的C1，2和肿瘤大小。使用统计分析和机械模型，我们将评估哪些测量值是AC处理结束时结果和NACT的最佳预测指标。