Magnetic Resonance Fingerprinting of Tumor Vascular Perfusion and Acidosis

点击翻译按钮获取中文摘要

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.