Methods for chemical exchange saturation transfer magnetic resonance imaging

Abstract

Chemical exchange saturation transfer (CEST) is a relatively new magnetic resonance imaging (MRI) acquisition technique that generates contrast dependent on tissue microenvironment, such as protein concentration and intracellular pH. CEST imaging has the potential to become an important biomarker in a wide range of disorders. As an indicator of tissue pH, CEST imaging may allow the identification of the ischemic penumbra in stroke, and predict chemo- and radiation therapy outcomes in cancer. As a marker of protein concentration, CEST may be able to delineate tumor margins without contrast enhancement, identify disease onset in Alzheimer's disease, and monitor cartilage repair therapies. Despite several promising pilot studies, CEST imaging has had limited clinical application due to two main technical challenges. First, CEST imaging is extremely sensitive to magnetic field inhomogeneity. Images suffer from large susceptibility artifacts unless specialized BO inhomogeneity correction methods are employed that tremendously increase scan time. Second, the CEST contrast cannot be separated from the intrinsic macromolecular magnetization transfer (MT) asymmetry and brain images reflect the MT properties of white and gray matter rather than the desired protein and pH contrast. We have developed a novel CEST imaging acquisition scheme, dubbed saturation with frequency alternating RF irradiation (SAFARI), designed to be insensitive to Bo inhomogeneity and MT asymmetry. Studies in healthy volunteers demonstrate that SAFARI is robust in the presence of BO inhomogeneity and eliminates the need for specialized BO correction, thereby reducing scan time. In addition, results show that SAFARI removes the confounding MT asymmetry. We applied SAFARI imaging towards the study of the saturation transfer contrast in patients with high grade glioma. Results show that the contrast in brain tumors, which was previously attributed to an increase in the CEST signal from amide protons due to an elevated protein concentration, is instead the result of the loss of MT asymmetry found in the normal brain. Therefore, our work has lead to a new understanding of the different sources of signal in saturation transfer images of the brain with important implications for the design and analysis of future CEST studies of brain tumors.