Creative applications of pulse techniques can provide a way to increase detectability and specificity of CEST contrast. In this presentation, we will discuss the advantages and limitations of several pulsed CEST techniques including pulsed saturation, chemical exchange rotation transfer (CERT), frequency labeled exchange (FLEX), and variable delay multi-pulse (VDMP) methods.
· The longer T2 of small molecule CEST agents allows for the design of novel pulse sequences for detection;
· Both saturation and excitation can be used to label CEST agents;
· Design of pulsed CEST techniques can aid in the separation of multiple magnetization transfer mechanisms.
Outcome objectives
After this presentation, participants should be able to:
· Understand the similarities and differences between CEST and conventional magnetization transfer contrast;
· Realize the power and limitations of several pulsed CEST technologies;
· Choose the appropriate saturation/excitation scheme according to the CEST agent/molecules of interest.
CEST labeling is similar to conventional magnetization transfer contrast (MTC). Therefore traditional CEST labeling is achieved by continuous wave saturation or pulsed saturation when scanner hardware duty cycle and specific absorption rates become limiting factors. In fact, CEST MRI is more versatile than MTC because the exchangeable protons on smaller molecules have longer lifetimes (T2) than the protons on the semisolid macromolecules that are responsible for MTC.(1) This property enables the use of spectroscopic techniques for signal editing. The longer lifetime allows one to encode protons during the evolution of transverse magnetization. This will not work for MTC since the signal dephases rapidly in the transverse plane. In this presentation we will discuss several pulsed CEST technologies that can compensate for scanner hardware constraints, improve CEST detection limits, or separate different exchange pathways.
We will discuss two classes of pulse sequence for CEST MRI: Saturation based and excitation based exchange transfer sequences. Saturation based sequences include contrast prepared off (2-4) and on (5) resonance saturation and pulsed steady state saturation transfer methods.(6) For excitation based sequences we will talk about methodologies such as chemical exchange rotation transfer (CERT)(7,8), frequency labeled exchange transfer (FLEX)(9,10), variable delay multi-pulse (VDMP)(11,12) and transfer rate edited CEST (TRE-CEST)(13).
1. van Zijl PCM, Sehgal AA. Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI. eMagRes 2016; 5(2): 1307-1332 DOI: 10.1002/9780470034590.emrstm1482
2. Pike GB, Glover GH, Hu BS, Enzmann DR. Pulsed magnetization transfer spin-echo MR imaging. Journal of magnetic resonance imaging : JMRI 1993;3(3):531-539.
3. Hu BS, Conolly SM, Wright GA, Nishimura DG, Macovski A. Pulsed saturation transfer contrast. Magnetic resonance in medicine 1992;26(2):231-240.
4. Pike GB. Pulsed magnetization transfer contrast in gradient echo imaging: a two-pool analytic description of signal response. Magnetic resonance in medicine 1996;36(1):95-103.
5. Vinogradov E, Zhang S, Lubag A, Balschi JA, Sherry AD, Lenkinski RE. On-resonance low B1 pulses for imaging of the effects of PARACEST agents. Journal of magnetic resonance (San Diego, Calif : 1997) 2005;176(1):54-63.
6. Jones CK, Polders D, Hua J, Zhu H, Hoogduin HJ, Zhou J, Luijten P, van Zijl PC. In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T. Magnetic resonance in medicine 2012;67(6):1579-1589.
7. Zu Z, Janve VA, Xu J, Does MD, Gore JC, Gochberg DF. A New Method for Detecting Exchanging Amide Protons Using Chemical Exchange Rotation Transfer. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine 2013;69(3):637-647.
8. Zu Z, Xu J, Li H, Chekmenev EY, Quarles CC, Does MD, Gore JC, Gochberg DF. Imaging amide proton transfer and nuclear overhauser enhancement using chemical exchange rotation transfer (CERT). Magnetic resonance in medicine 2014;72(2):471-476.
9. Friedman JI, McMahon MT, Stivers JT, Van Zijl PC. Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer. Journal of the American Chemical Society 2010;132(6):1813-1815.
10. Yadav NN, Jones CK, Xu J, Bar-Shir A, Gilad AA, McMahon MT, van Zijl PCM. Detection of rapidly exchanging compounds using on-resonance frequency labeled exchange (FLEX) transfer. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine 2012;68(4):1048-1055.
11. Xu J, Yadav NN, Bar-Shir A, Jones CK, Chan KWY, Zhang J, Walczak P, McMahon MT, van Zijl PCM. Variable delay multi-pulse train for fast chemical exchange saturation transfer and relayed-nuclear overhauser enhancement MRI. Magnetic resonance in medicine 2014;71(5):1798-1812.
12. Xu J, Chan KWY, Xu X, Yadav N, Liu G, van Zijl PCM. On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules. Magnetic resonance in medicine 2017;77(2): 730–739.
13. Friedman JI, Xia D, Regatte RR, Jerschow A. Transfer Rate Edited Experiment for the Selective Detection of Chemical Exchange via Saturaion Transfer (TRE-CEST). Journal of magnetic resonance 2015;256:43-51.