CEST sources

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To get the basic idea of CEST here a list of recent reviews. Best to for beginners is maybe

Chemical exchange saturation transfer (CEST): what is in a name and what isn't? by Peter van Zijl and NirbhayYadav.

or

Wu B, Warnock G, Zaiss M, Lin C, Chen M, Zhou Z, Mu L, Nanz D, Tuura R, Delso G. An overview of CEST MRI for non-MR physicists. EJNMMI Phys. 2016 Dec;3(1):19. doi: 10.1186/s40658-016-0155-2. Epub 2016 Aug 26. PMID: 27562024; PMCID: PMC4999387.

 

Here the list of reviews in chronologic order:

Zaiss M, Jin T, Kim SG, Gochberg DF. Theory of chemical exchange saturation transfer MRI in the context of different magnetic fields. NMR Biomed. 2022 Nov;35(11):e4789. doi: 10.1002/nbm.4789. Epub 2022 Jul 16. PMID: 35704180.


Zhou Y, Bie C, van Zijl PCM, Yadav NN. The relayed nuclear Overhauser effect in magnetization transfer and chemical exchange saturation transfer MRI. NMR Biomed. 2022 May 31:e4778. doi: 10.1002/nbm.4778. Epub ahead of print. PMID: 35642102; PMCID: PMC9708952.

Xu J, Chung JJ, Jin T. Chemical exchange saturation transfer imaging of creatine, phosphocreatine, and protein arginine residue in tissues. NMR Biomed. 2022 Jan 3:e4671. doi: 10.1002/nbm.4671. Epub ahead of print. PMID: 34978371; PMCID: PMC9250548.


Zhou J, Zaiss M, Knutsson L, Sun PZ, Ahn SS, Aime S, Bachert P, Blakeley JO, Cai K, Chappell MA, Chen M, Gochberg DF, Goerke S, Heo HY, Jiang S, Jin T, Kim SG, Laterra J, Paech D, Pagel MD, Park JE, Reddy R, Sakata A, Sartoretti-Schefer S, Sherry AD, Smith SA, Stanisz GJ, Sundgren PC, Togao O, Vandsburger M, Wen Z, Wu Y, Zhang Y, Zhu W, Zu Z, van Zijl PCM. Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors. Magn Reson Med. 2022 Aug;88(2):546-574. doi: 10.1002/mrm.29241. Epub 2022 Apr 22. PMID: 35452155; PMCID: PMC9321891.

van Zijl PCM, Lam WW, Xu J, Knutsson L, Stanisz GJ. Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI. Features and analysis of the field-dependent saturation spectrum. Neuroimage. 2018 Mar;168:222-241. doi: 10.1016/j.neuroimage.2017.04.045. Epub 2017 Apr 21. PMID: 28435103; PMCID: PMC5650949.

Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss ("saturation"). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum. In tissue, these Z-spectra contain the convolution of multiple saturation transfer effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange contributions from protons in semi-solid and mobile macromolecules or tissue metabolites. As a consequence, their appearance depends on the magnetic field strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and length, and interpulse delay, which presents a major problem for quantification and reproducibility of MTC and CEST effects. The use of higher B0 can bring several advantages. In addition to higher detection sensitivity (signal-to-noise ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the saturation transferred to water to be retained longer. While MTC studies are non-specific at any field strength, CEST specificity is expected to increase at higher field because of a larger chemical shift dispersion of the resonances of interest (similar to MRS). In addition, shifting to a slower exchange regime at higher B0 facilitates improved detection of the guanidinium protons of creatine and the inherently broad resonances of the amine protons in glutamate and the hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due to the higher mobility of the contributing protons in CEST versus MTC, many new pulse sequences can be designed to more specifically edit for CEST signals and to remove MTC contributions.


Wu B, Warnock G, Zaiss M, Lin C, Chen M, Zhou Z, Mu L, Nanz D, Tuura R, Delso G. An overview of CEST MRI for non-MR physicists. EJNMMI Phys. 2016 Dec;3(1):19. doi: 10.1186/s40658-016-0155-2. Epub 2016 Aug 26. PMID: 27562024; PMCID: PMC4999387.

The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts. 

 

Phys Med Biol. 2013 Nov 21;58(22):R221-69.
**Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a
review of theoretical approaches and methods.**
Zaiss M, Bachert P.


Chemical exchange saturation transfer (CEST) of metabolite protons that undergo
exchange processes with the abundant water pool enables a specific contrast for
magnetic resonance imaging (MRI). The CEST image contrast depends on physical and
physiological parameters that characterize the microenvironment such as
temperature, pH, and metabolite concentration. However, CEST imaging in vivo is a
complex technique because of interferences with direct water saturation
(spillover effect), the involvement of other exchanging pools, in particular
macromolecular systems (magnetization transfer, MT), and nuclear Overhauser
effects (NOEs). Moreover, there is a strong dependence of the diverse effects on
the employed parameters of radiofrequency irradiation for selective saturation
which makes interpretation of acquired signals difficult. This review considers
analytical solutions of the Bloch–McConnell (BM) equation system which enable
deep insight and theoretical description of CEST and the equivalent off-resonant
spinlock (SL) experiments. We derive and discuss proposed theoretical treatments
in detail to understand the influence of saturation parameters on the acquired
Z-spectrum and how the different effects interfere and can be isolated in MR
Z-spectroscopy. Finally, we provide an overview of reported CEST effects in vivo
and discuss proposed methods and technical approaches applicable to in vivo CEST
studies on clinical MRI systems.

Curr Radiol Rep. 2013 Jun 1;1(2):102-114.
Chemical Exchange Saturation Transfer (CEST) Imaging: Description of Technique
and Potential Clinical Applications.
Kogan F(1), Hariharan H, Reddy R.

Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging
(MRI) contrast enhancement technique that enables indirect detection of
metabolites with exchangeable protons. Endogenous metabolites with exchangeable
protons including many endogenous proteins with amide protons, glycosaminoglycans
(GAG), glycogen, myo-inositol (MI), glutamate (Glu), creatine (Cr) and several
others have been identified as potential in vivo endogenous CEST agents. These
endogenous CEST agents can be exploited as non-invasive and non-ionizing
biomarkers of disease diagnosis and treatment monitoring. This review focuses on
the recent technical developments in endogenous in vivo CEST MRI from various
metabolites as well as their potential clinical applications. The basic
underlying principles of CEST, its potential limitations and new techniques to
mitigate them are discussed.



J Neuroimaging. 2013 Oct;23(4):526-32. doi: 10.1111/j.1552-6569.2012.00751.x.
Epub 2013 Feb 12.
Application of chemical exchange saturation transfer (CEST) MRI for endogenous
contrast at 7 Tesla.
Dula AN(1), Smith SA, Gore JC.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI)
indirectly images exchangeable solute protons resonating at frequencies different
than bulk water. These solute protons are selectively saturated using low
bandwidth RF irradiation and saturation is transferred to bulk water protons via
chemical exchange, resulting in an attenuation of the measured water proton
signal. CEST MRI is an advanced MRI technique with wide application potential due
to the ability to examine complex molecular contributions. CEST MRI at high field
(7 Tesla [7 T]) will improve the overall results due to increase in signal, T1
relaxation time, and chemical shift dispersion. Increased field strength
translates to enhanced quantification of the metabolite of interest, allowing
more fundamental studies on underlying pathophysiology. CEST contrast is affected
by several tissue properties, such as the concentrations of exchange partners and
their rate of proton exchange, whose effects have been examined and explored in
this review. We have highlighted the background of CEST MRI, typical
implementation strategy, and complications at 7 T.

Copyright © 2013 by the American Society of Neuroimaging.


NMR Biomed. 2013 Jul;26(7):810-28. doi: 10.1002/nbm.2899. Epub 2013 Jan 10.
Nuts and bolts of chemical exchange saturation transfer MRI.
Liu G(1), Song X, Chan KW, McMahon MT.

Chemical exchange saturation transfer (CEST) has emerged as a novel MRI contrast
mechanism that is well suited for molecular imaging studies. This new mechanism
can be used to detect small amounts of contrast agent through the saturation of
rapidly exchanging protons on these agents, allowing a wide range of
applications. CEST technology has a number of indispensable features, such as the
possibility of simultaneous detection of multiple 'colors' of agents and of
changes in their environment (e.g. pH, metabolites, etc.) through MR contrast.
Currently, a large number of new imaging schemes and techniques are being
developed to improve the temporal resolution and specificity and to correct for
the influence of B0 and B1 inhomogeneities. In this review, the techniques
developed over the last decade are summarized with the different imaging
strategies and post-processing methods discussed from a practical point of view,
including the description of their relative merits for the detection of CEST
agents. The goal of the present work is to provide the reader with a fundamental
understanding of the techniques developed, and to provide guidance to help refine
future applications of this technology. This review is organized into three main
sections ('Basics of CEST contrast', 'Implementation' and 'Post-processing'), and
also includes a brief Introduction and Summary. The 'Basics of CEST contrast'
section contains a description of the relevant background theory for saturation
transfer and frequency-labeled transfer, and a brief discussion of methods to
determine exchange rates. The 'Implementation' section contains a description of
the practical considerations in conducting CEST MRI studies, including the choice
of magnetic field, pulse sequence, saturation pulse, imaging scheme, and
strategies to separate magnetization transfer and CEST. The 'Post-processing'
section contains a description of the typical image processing employed for B0
/B1 correction, Z-spectral interpolation, frequency-selective detection and
improvement of CEST contrast maps.
Copyright © 2013 John Wiley & Sons, Ltd.



 J Magn Reson. 2013 Apr;229:155-72. doi: 10.1016/j.jmr.2012.11.024. Epub 2012 Dec
CEST: from basic principles to applications, challenges and opportunities.
Vinogradov E(1), Sherry AD, Lenkinski RE.

Chemical Exchange Saturation Transfer (CEST) offers a new type of contrast for
MRI that is molecule specific. In this approach, a slowly exchanging NMR active
nucleus, typically a proton, possessing a chemical shift distinct from water is
selectively saturated and the saturated spin is transferred to the bulk water via
chemical exchange. Many molecules can act as CEST agents, both naturally
occurring endogenous molecules and new types of exogenous agents. A large variety
of molecules have been demonstrated as potential agents, including small
diamagnetic molecules, complexes of paramagnetic ions, endogenous macromolecules,
dendrimers and liposomes. In this review we described the basic principles of the
CEST experiment, with emphasis on the similarity to earlier saturation transfer
experiments described in the literature. Interest in quantitative CEST has also
resulted in the development of new exchange-sensitive detection schemes. Some
emerging clinical applications of CEST are described and the challenges and
opportunities associated with translation of these methods to the clinical
environment are discussed.

Copyright © 2012 Elsevier Inc. All rights reserved.


Magn Reson Med. 2011 Apr;65(4):927-48. doi: 10.1002/mrm.22761. Epub 2011 Feb 17.
Chemical exchange saturation transfer (CEST): what is in a name and what isn't?
van Zijl PC, Yadav NN.

Chemical exchange saturation transfer (CEST) imaging is a relatively new magnetic
resonance imaging contrast approach in which exogenous or endogenous compounds
containing either exchangeable protons or exchangeable molecules are selectively
saturated and after transfer of this saturation, detected indirectly through the
water signal with enhanced sensitivity. The focus of this review is on basic
magnetic resonance principles underlying CEST and similarities to and differences
with conventional magnetization transfer contrast. In CEST magnetic resonance
imaging, transfer of magnetization is studied in mobile compounds instead of
semisolids. Similar to magnetization transfer contrast, CEST has contributions of
both chemical exchange and dipolar cross-relaxation, but the latter can often be
neglected if exchange is fast. Contrary to magnetization transfer contrast, CEST
imaging requires sufficiently slow exchange on the magnetic resonance time scale
to allow selective irradiation of the protons of interest. As a consequence,
magnetic labeling is not limited to radio-frequency saturation but can be
expanded with slower frequency-selective approaches such as inversion, gradient
dephasing and frequency labeling. The basic theory, design criteria, and
experimental issues for exchange transfer imaging are discussed. A new
classification for CEST agents based on exchange type is proposed. The potential
of this young field is discussed, especially with respect to in vivo application
and translation to humans.

Copyright © 2011 Wiley-Liss, Inc.


Contrast Media Mol Imaging. 2010 Mar-Apr;5(2):78-98. doi: 10.1002/cmmi.369.
Encoding the frequency dependence in MRI contrast media: the emerging class of
CEST agents.

Terreno E(1), Castelli DD, Aime S.

CEST agents represent a very promising class of MRI contrast media as they encode
a frequency dependence that is not like the classical relaxation-based agents.
This peculiar property enables novel applications such as the detection of more
than one agent in the same MR image as well as the set-up of ratiometric methods
for the quantitative assessment of physico-chemical and biological parameters
that characterize the micro-environment in which they are distributed. This
survey is aimed at providing the reader with the basic properties and the
potential of these compounds. Fundamental aspects, such as the theoretical basis
of the saturation transfer via chemical exchange, the generation of the CEST
contrast, the classification and sensitivity of CEST agents, and some
representative examples displaying their potential in the field of MR-molecular
imaging, are presented and discussed in detail.

2010 John Wiley & Sons, Ltd.


Annu Rev Biomed Eng. 2008;10:391-411. doi:
10.1146/annurev.bioeng.9.060906.151929.
Chemical exchange saturation transfer contrast agents for magnetic resonance
imaging.
Sherry AD(1), Woods M.

Magnetic resonance imaging (MRI) contrast agents have become an important tool in
clinical medicine. The most common agents are Gd(3+)-based complexes that shorten
bulk water T(1) by rapid exchange of a single inner-sphere water molecule with
bulk solvent water. Current gadolinium agents lack tissue specificity and
typically do not respond to their chemical environment. Recently, it has been
demonstrated that MR contrast may be altered by an entirely different mechanism
based on chemical exchange saturation transfer (CEST). CEST contrast can
originate from exchange of endogenous amide or hydroxyl protons or from
exchangeable sites on exogenous CEST agents. This has opened the door for the
discovery of new classes of responsive agents ranging from MR gene reporter
molecules to small molecules that sense their tissue environment and respond to
biological events.

 

Progress in Nuclear Magnetic Resonance Spectroscopy, Volume 48, Issues 2–3, 30 May 2006, Pages 109-136, ISSN 0079-6565,
Chemical exchange saturation transfer imaging and spectroscopy
http://dx.doi.org/10.1016/j.pnmrs.2006.01.001.
Jinyuan Zhou, Peter C.M. van Zijl,
CEST sources

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