A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Abstract

Chemical exchange saturation transfer (CEST) MRI is a promising molecular imaging tool which allows the specific detection of metabolites that contain exchangeable amide, amine, and hydroxyl protons. Decades of development have progressed CEST imaging from an initial concept to a clinical imaging tool that is used to assess tumor metabolism. The first translation efforts involved brain imaging, but this has now progressed to imaging other body tissues. In this review, we summarize studies using CEST MRI to image a range of tumor types, including breast cancer, pelvic tumors, digestive tumors, and lung cancer. Approximately two thirds of the published studies involved breast or pelvic tumors which are sites that are less affected by body motion. Most studies conclude that CEST shows good potential for the differentiation of malignant from benign lesions with a number of reports now extending to compare different histological classifications along with the effects of anti-cancer treatments. Despite CEST being a unique ‘label-free’ approach with a higher sensitivity than MR spectroscopy, there are still some obstacles for implementing its clinical use. Future research is now focused on overcoming these challenges. Vigorous ongoing development and further clinical trials are expected to see CEST technology become more widely implemented as a mainstream imaging technology.

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

“…The basics of APTw imaging have been explained in several previous review articles 4–21 . Briefly, APTw imaging is generally obtained by RF saturation labeling of the water‐exchangeable backbone amide proton pool of proteins and peptides, followed by a physical transfer (chemical exchange) of these saturated amide protons to bulk water protons, resulting in a decrease in their magnetization.…”

“…The basics of APTw imaging have been explained in several previous review articles. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Briefly, APTw imaging is generally obtained by RF saturation labeling of the water-exchangeable backbone amide proton pool of proteins and peptides, followed by a physical transfer (chemical exchange) of these saturated amide protons to bulk water protons, resulting in a decrease in their magnetization. Theoretically, the CEST effect of amide protons can be expressed in terms of a so-called amide proton transfer ratio (APTR), a formulation that describes the different parameters on which the CEST effect depends.…”

“…Amide proton transfer‐weighted (APTw) imaging is a molecular MRI technique that generates image contrast based on endogenous mobile proteins and peptides in tissue 1,2 . As a type of CEST imaging, 3 the principles and applications of APTw imaging have been reviewed in several articles 4–21 . Key abbreviations and nomenclatures used in the field of APTw imaging are listed in Table 1.…”

“…1,2 As a type of CEST imaging, 3 the principles and applications of APTw imaging have been reviewed in several articles. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Key abbreviations and nomenclatures used in the field of APTw imaging are listed in Table 1. Data from numerous institutions worldwide have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnoses, such as the detection and grading of tumors, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] the assessment of treatment effect versus tumor recurrence, [38][39][40][41][42][43][44][45] prognosis related to tumor progression and survival, [46]…”

Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response

“…Clinically relevant molecular information can be obtained using a variety of imaging modalities, including positron emission and single photon emission computed tomographic imaging (PET and SPECT), ultrasound, optical imaging, X-ray computed tomography (CT), and magnetic resonance imaging (MRI) [ 37 , 47 , 48 , 49 , 50 , 51 , 52 ]. The latter stands out due to several characteristics: (1) It is an extremely versatile modality, where the image contrast can be programmed to emphasize a variety of biophysical properties; (2) It provides excellent soft tissue contrast, at any tissue depth; (3) It does not require the use of ionizing radiation; (4) It can detect molecular-based phenomena using contrast enhancing materials (similar to PET, SPECT, and ultrasound) but also via endogenous (injection-free) mechanisms.…”