Abstract
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detects molecules in their natural forms in a sensitive and non-invasive manner. This makes it a robust approach to assess brain tumors and related molecular alterations using endogenous molecules, such as proteins/peptides, and drugs approved for clinical use. In this review, we will discuss the promises of CEST MRI in the identification of tumors, tumor grading, detecting molecular alterations related to isocitrate dehydrogenase (IDH) and O-6-methylguanine-DNA methyltransferase (MGMT), assessment of treatment effects, and using multiple contrasts of CEST to develop theranostic approaches for cancer treatments. Promising applications include (i) using the CEST contrast of amide protons of proteins/peptides to detect brain tumors, such as glioblastoma multiforme (GBM) and low-grade gliomas; (ii) using multiple CEST contrasts for tumor stratification, and (iii) evaluation of the efficacy of drug delivery without the need of metallic or radioactive labels. These promising applications have raised enthusiasm, however, the use of CEST MRI is not trivial. CEST contrast depends on the pulse sequences, saturation parameters, methods used to analyze the CEST spectrum (i.e., Z-spectrum), and, importantly, how to interpret changes in CEST contrast and related molecular alterations in the brain. Emerging pulse sequence designs and data analysis approaches, including those assisted with deep learning, have enhanced the capability of CEST MRI in detecting molecules in brain tumors. CEST has become a specific marker for tumor grading and has the potential for prognosis and theranostics in brain tumors. With increasing understanding of the technical aspects and associated molecular alterations detected by CEST MRI, this young field is expected to have wide clinical applications in the near future.
Highlights
APTw refers to MTRasym at 3.5 ppm, APT refers to Chemical exchange saturation transfer (CEST) at 3.5 ppm, NOE refers to CEST at −3.5 ppm, unless the offset is indicated
In the considerations of the presence of the BBB and the efficacy of drugs under physiological environment, we recently developed a CEST magnetic resonance imaging (MRI)-guided nose-to-brain drug delivery system based on CEST detectable liposomes [156]
The three-offset method is more suitable for CEST studies at high fields as it relies on a clear delineation of CEST peaks [185]
Summary
The inclusion of new multiple assessment parameters could address challenges in brain tumor diagnosis, treatment planning, and evaluation. Some of these molecular aldiagnosis, treatment planning, and evaluation. Chemical exchange saturation transfer (CEST) is an emerging is an emerging molecular imaging approach which enables the assessments of molecular molecular imaging approach which enables the assessments of molecular alterations in alterations in brain tumors [3–45]. CEST detects molecules via proton exchange with bulk water (110 M) which is abundant in vivo. MRS detects the distinct chemical environments of molecules while molecular imaging. This review will focus on the promises of CEST imaging of brain tumors, non-metallic contrast agents, clinical agents and biomaterials for drug delivery, and the challenges of CEST clinical applications
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