The goal of this educational presentation is to discuss the important contributions that CEST MRI can have for clinical-translational studies, by highlighting the unique contrasts available and examining the current applications of CEST MRI in the literature. We will further discuss the potential limitations for more clinically viable adoption of CEST and discuss the opportunities to overcome these limitations, including some studies that have begun to take the clinical leap. We will close by discussing the potential impact of a unique contrast to clinical-translational studies of the human condition.
Chemical Exchange Saturation Transfer (CEST) is a unique MRI technique that has been available to the MRI community for a number of years and its goal is to elicit sensitive (and potentially specific) contrast from small, mobile molecules and chemical compounds. In fact, it can be argued that CEST MRI is one of the few molecular imaging MRI techniques on the market. The contrast in CEST results from transfer of selective labeling (saturation) of exchangeable protons (chemical exchange) with surrounding water and has been utilized in the research community to study stroke, cancer, psychiatric, and neurodegenerative diseases in humans and animals. The question is, how close is CEST MRI to clinical adoption and, a better question is what does clinical adoption of CEST MRI look like? The goal of this presentation is to discuss the “almost clinical” applications of CEST MRI and to ask the question of what is necessary to take the next step.
CEST MRI experiments seek to obtain indirect information about the concentration and exchange of labile protons associated with mobile molecules through direct chemical exchange. In a CEST experiment, labile protons, resonating at a specific offset frequency can be selectively saturated with a narrow bandwidth RF irradiation at an offset frequency sensitive to the resonance frequency of the labile protons of interest. If the labile protons can be efficiently saturated (slow to intermediate exchange rates) and have concentrations that are sufficiently large, then after an RF saturation, we observe an attenuation of the measured water signal, related to the concentration and exchange rate of the labile protons.1 Typically, a CEST experiment consists of obtaining multiple data points at different RF irradiation offsets and powers (CEST z-spectrum) and then the magnitude of the CEST effect is characterized through either asymmetry, fitting, or advanced spectral analyses.
Generally, CEST has been exploited to derive indices reflective of sensitivity to amide2 (so-called amide proton transfer), amine (gluCEST)3 or hydroxyl protons (MiCEST4 or GAG-CEST5), and more recently for compounds such as creatine6. Being sensitive to these associated protons provides an opportunity to probe aspects of cancer, stroke, multiple sclerosis, degenerative disk and cartilage diseases, and other conditions such as epilepsy. However, the ability to translate CEST MRI to true clinical adoption has lagged behind other techniques for a variety of reasons. That having been said, there has been tremendous achievements over the past few years that have, for the first time, provided glimpses of what the future may be for clinical adoption of CEST methods. Nevertheless, while glimpses are encouraging, there are still some hurdles to overcome, thus the focus of this presentation is on the “almost clinical” picture, but to encourage thinking about how close we are to utilizing CEST to make a clinical impact.
· Description of CEST in the context of translational MRI
· Overview of the unique contrasts that CEST can offer
· How can CEST be used in disease, and what is missing from conventional MRI
· Improvements that could be made to achieve clinical-translational impact
· Discussion of the value of CEST in a more clinical context
1. van Zijl PC, Yadav NN. Chemical exchange saturation transfer (CEST): what is in a name and what isn’t? Magn Reson Med. 2011 Apr;65(4):927-48
2. Zhou J, Payen JF, Wilson DA, Traystman RJ, van Zijl PC. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 2003 Aug;9(8):1085-90.
3. Cai K, Haris M, Singh A, Kogan F, Greenberg JH, Hariharan H, Detre JA, Reddy R. Magnetic resonance imaging of glutamate. Nat Med. 2012 Jan 22;18(2):302-6
4. Haris M, Cai K, Singh A, Hariharan H, Reddy R. In vivo mapping of brain myo-inositol. Neuroimage. 2011 Feb 1;54(3):2079-85
5. Singh A, Haris M, Cai K, Kassey VB, Kogan F, Reddy D, Hariharan H, Reddy R. Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med. 2012 Aug;68(2):588-94
6. Kogan F, Haris M, Singh A, Cai K, Debrosse C, Nanga RP, Hariharan H, Reddy R. Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer. Magn Reson Med. 2014 Jan;71(1):164-72