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. 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 relatively new MRI technique that has been utilized in the study of stroke, cancer, neurodegenerative diseases in both humans and animal models. A CEST MRI experiments seeks to obtain indirect information about the concentration and exchange rate of labile protons associated with mobile molecules through the principle of direct chemical exchange. In a CEST experiment, labile protons, resonating at a specific range of offset frequencies can be selectively saturated with a low-power, narrow bandwidth RF irradiation at an offset frequency sensitive to the resonance frequency of the labile protons of interest. If the labile protons are in slow to intermediate exchange and have concentrations that are sufficiently large to be detected, then after an RF irradiation, an observed attenuation of the water signal can be observed, which is related to the concentration and exchange rate of the exchanging protons.1
Typically a CEST experiment consists of obtaining signals at different RF irradiation offsets and powers (so-called CEST z-spectrum) and then the magnitude of the CEST effect is characterized through either asymmetry analysis, lorentzian fitting, or more sophisticated modeling of the CEST z-spectra.
Generally, CEST has been exploited to derive sensitivity to amide protons2 (so-called amide proton transfer), amine protons (gluCEST3) or hydroxyl protons (MiCEST4 or GAG-CEST5), and more recently for compounds such as creatine6. For a number of years, CEST has been studied in animal models, and recently some CEST experiments have been deployed in humans in the study of cancer, stroke, multiple sclerosis, degenerative disk and cartilage diseases, and other conditions such as epilepsy.
The challenge, however, is in utilizing CEST in a translational fashion. While many studies have utilized CEST in humans to derive measures sensitive to the pathology of interest, the adoption of CEST to clinical studies has not yet been wide. Some reasons for this are the length of time that it takes to obtain high-quality CEST data, low spatial resolution, limitations on MRI hardware and software, and lack of consensus on quantifying CEST data in the presence of changes in relaxation, magnetization transfer (MT) and NOE effects. Furthermore, in disease, concomitant tissue changes may further complicate CEST analysis. Therefore, there is a great desire to obtain high quality, rapid, optimized CEST data in patient cohorts, yet CEST applications to clinical populations are still in their infancy.
· 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