Magnetic Resonance Fingerprinting of Tumor Vascular Perfusion and Acidosis

肿瘤血管灌注和酸中毒的磁共振指纹图谱

基本信息

批准号：
10593285
负责人：
Christopher A Flask
金额：
$ 67.38万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10593285
关键词：
3-Dimensional Acidosis Address Algorithms Animal Model Animals Bicarbonates Biometry Blood Vessels Breast Cancer Model Cancer Model Cancer Patient Clinic Combretastatin A4 Phosphate Contrast Media Development Dictionary Dose Drug Kinetics Early Diagnosis Environment Esomeprazole Evaluation Fingerprint Goals Histopathology Hypoxia Image Injections Lead Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Maps Measurement Measures Metformin Methodology Methods Microelectrodes Modeling Monitor Mus Patients Perfusion Preparation Quantitative Evaluations Radiation therapy Radiology Specialty Recovery Relaxation Reporting Reproducibility Research Research Personnel Rodent Model Series Solid Neoplasm Techniques Therapeutic Translating Validation Variant Xenograft procedure anticancer treatment cancer diagnosis cancer therapy clinical translation clinically relevant contrast enhanced design experience experimental study extracellular human model imaging modality improved in vivo innovation metaiodobenzylguanidine novel strategies pancreas xenograft pancreatic neoplasm preclinical imaging response temporal measurement treatment response tumor tumor diagnosis tumor microenvironment

项目摘要

PROJECT DESCRIPTION As a major limitation in contrast enhanced MRI studies is that current MRI methods lack the combination of accuracy, precision, and temporal resolution to quantitatively measure contrast agents in vivo. We have addressed this problem by developing dynamic Magnetic Resonance Fingerprinting (MRF) methods that can rapidly measure T1 or T2 relaxation times with outstanding accuracy and precision (Radiology, 2021). Our key MRF innovations include a combination of highly undersampled spiral trajectories, low flip angles and multiple magnetization preparations to avoid errors from B1 inhomogeneities and limited T2 sensitivity. Our MRF methods can also be adapted to simultaneously detect one or two MRI contrast agents. We have recently demonstrated that a new T1-MRF method can be used to dynamically generate quantitative T1 maps with very fast temporal resolution (~2.5 seconds) during an in vivo Dynamic Contrast Enhanced (DCE) – MRF experiment. In Aim 1, we will first optimize a new 3D T1-MRF method to evaluate tumor vascular perfusion (ktrans) with high accuracy and precision in mouse cancer models. We will then evaluate this Dynamic Contrast Enhanced (DCE) – MRF method by measuring changes in vascular perfusion in mouse cancer models treated with either a vascular disrupting agent or radiotherapy. Our objective is to demonstrate that DCE- MRF provides superior precision in comparison to standard DCE-MRI methods providing the opportunity to more sensitively detect the early response to treatment, which can then be translated to the clinic. We have also demonstrated that a similar dynamic MRF method can be used to simultaneously measure the concentration of a T1 contrast agent and a T2 contrast agent within an in vivo tumor model with outstanding accuracy and precision (Scientific Reports 2017 and 2019). In Aim 2, we will develop a similar two-agent MRF method to simultaneously detect a pH-dependent T1 contrast agent and a pH-independent T2 contrast agent to measure extracellular pH (pHe) in tumor models. We will apply our pHe-MRF approach to monitor changes in tumor pHe after administering treatments that raise and lower tumor acidosis to validate our methodology. Our deliverable for this project is a new adaptable, dynamic 3D MRF approach to quantitative measure one or two MRI contrast agents in vivo. These new 3D DCE-MRF and pHe-MRF methods are the key innovation of our research. We have developed a rigorous research approach with an emphasis on quantitative evaluations and validations using multiple established mouse cancer models and therapeutic strategies. We have also assembled a team of strong and highly experienced investigators, and we have an exceptional research environment for our studies. Importantly, this successful preclinical imaging project will immediately lead to clinical translation of the DCE-MRF method for use in cancer patients and will provide the opportunity for effective pHe assessments in animal models and eventually in patients.

项目描述对比增强 MRI 研究的一个主要限制是当前的 MRI 方法缺乏结合我们拥有定量测量体内造影剂的准确性、精确度和时间分辨率。通过开发动态磁共振指纹（MRF）方法解决了这个问题，该方法可以以出色的准确性和精密度快速测量 T1 或 T2 弛豫时间（放射学，2021 年）。 MRF 创新包括高度欠采样螺旋轨迹、低翻转角和多个磁化准备以避免 B1 不均匀性和有限的 T2 灵敏度造成的误差。也可以适用于同时检测一种或两种 MRI 造影剂。我们最近证明了一种新的 T1-MRF 方法可用于动态生成体内动态对比期间具有非常快的时间分辨率（约 2.5 秒）的定量 T1 图增强型 (DCE) – MRF 实验在目标 1 中，我们将首先优化一种新的 3D T1-MRF 方法来评估肿瘤。然后我们将在小鼠癌症模型中进行高精度的血管灌注（ktrans）评估。动态对比度增强 (DCE) – 通过测量小鼠癌症血管灌注变化的 MRF 方法用血管破坏剂或放射疗法治疗的模型我们的目标是证明 DCE-。与标准 DCE-MRI 方法相比，MRF 提供了卓越的精度，从而提供了更多机会敏感地检测对治疗的早期反应，然后将其转化为临床。我们还证明了类似的动态 MRF 方法可用于同时测量体内肿瘤模型中 T1 造影剂和 T2 造影剂的浓度具有出色的准确性和精确度（2017 年和 2019 年科学报告）在目标 2 中，我们将开发类似的双代理 MRF。同时检测 pH 依赖性 T1 造影剂和 pH 无关 T2 造影剂的方法我们将应用 pHe-MRF 方法来监测肿瘤模型中的细胞外 pH (pHe) 变化。在进行提高和降低肿瘤酸中毒的治疗后，测量肿瘤 pHe 以验证我们的方法。我们为该项目交付的成果是一种新的适应性强的动态 3D MRF 方法，用于定量测量或两种 MRI 造影剂在体内这些新的 3D DCE-MRF 和 pHe-MRF 方法是关键创新。我们的研究制定了严格的研究方法，重点是定量评估。我们还使用多种已建立的小鼠癌症模型和治疗策略进行了验证。组建了一支强大且经验丰富的研究人员团队，我们拥有出色的研究重要的是，这个成功的临床前成像项目将立即带来结果。 DCE-MRF 方法在癌症患者中的临床转化将为有效的治疗提供机会在动物模型中以及最终在患者中进行 pHe 评估。