Absolute Quantitation for MR Molecular Imaging of Angiogenesis

Abstract

Medical imaging is undergoing a transition from an art that is used to make static images of human physiology into a scientific tool that employs advanced techniques to measure clinically relevant data. Recently, the role of magnetic resonance imaging in cardiovascular and oncological research has grown, largely due to the implementation of new quantitative techniques in the clinic. Magnetic resonance imaging (MRI) and spectroscopy (MRS) are particularly rich in their capability to quantify both physiology and disease via biomarker detection. While this is true for many applications of MRI in cardiovascular and oncological research, 19F MR molecular imaging is particularly useful when coupled to the use of emerging site-targeted molecular imaging agents for diagnosis and therapy, such as αvβ3 integrin-targeted perfluorocarbon (PFC) nanoparticle (NP) emulsions. Unfortunately, the radiological world is realizing that although image quality may be consistently high, the absolute quantitative values being calculated vary widely across time, techniques, laboratories, and imaging platforms. The overall objective of this work is to advance the state of the art for 19F MR molecular imaging of perfluorocarbon nanoparticle emulsion contrast agents. To reach this objective, three specific aims have been identified: (1) to create new tools and techniques for 19F MR molecular imaging of PFC nanoparticles, (2) to develop translatable procedures for absolute quantification of 19F nuclei with MR molecular imaging, and (3) to evaluate the potential for clinical translation with ex vivo and in vivo preclinical experiments. Robust, standardized techniques are developed in this work to improve the accuracy of in vivo quantitative 19F MR molecular imaging, validate system performance, calibrate measurements to ensure repeatability of these quantitative metrics, and evaluate the potential for clinical translation. As these quantitative metrics become routine in medical imaging procedures, these standardized calibrations and techniques are expected to be critical for accurate interpretation of underlying pathophysiology. This will also impact the development of new therapies and diagnostic techniques/agents by reducing the variability of image-based measurements, thereby increasing the impact of the studies and reducing the overall time and cost to translate new technologies into the clinic