The idea of chemical exchange
saturation transfer (CEST) as a method to detect small concentrations of
metabolites, based on magnetization exchange between exchangeable protons and
water, was first suggested by Balaban and co-workers 16 years ago [1]. Selective
long CW irradiation on the exchangeable protons on the metabolites causes their
saturation, and the magnetization flowing from the water protons by chemical
exchange causing reduction in the water peak. Thus, millimolar concentrations
of metabolites induce changes in the much larger water proton pool (about 110
molar). Recently this idea started be used for imaging with multitude of
applications.
CEST agents can be divided into the
following classes: diamagnetic CEST (diaCEST), paramagnetic CEST (paraCEST),
and hyperpolarized CEST (hyperCEST). In the talk examples will be given for the
diaCEST. A number of excellent reviews have been written on the CEST method and
applications [2-7].
diaCEST can be further divided into
the classes of endogenous and exogenous agents. Lee et al give a survey of the
in vitro CEST properties of endogenous CEST agents that are commonly found in
biological tissues and organs at 3T and 7T and at various pH values [8].
Examples of applications of
endogenous agents are:
glycoCEST for the detection glycogen, the primary storage form of glucose in mammalian tissues [9];
gagCEST for the glycosaminoglycans
detection in cartilage and in intervertebral discs [10-13];
gluCEST for detection of glutamate,
which is the major excitatory neurotransmitter in the brain and its
applications for Alzheimer's disease and epilepsy [14-20];
Amide Proton Transfer (APT) based on
proton exchange from amide NH groups from proteins [21,22];
crCEST, for creatine in muscle
tissues [23-27];
miCEST: Myo-inositol is a marker of glial cells proliferation. Its
concentration is altered in many brain disorderes and has been shown to
increase in early Alzheimer’s disease (AD) pathology [28-29];
sialoCEST and mucCEST: Sialic acid (SA)
residues are attached to cell-surfaces and proteins as in glycoproteins, and
peptides as in mucopolysaccharides. The mammalian central nervous system has
the highest concentration of SA, most of which is present in gangliosides and
glycoproteins. Mucins are highly glycosylated proteins containing SA residues
that are over-expressed in many types of tumors and are associated with their malignancy [30-31].
Examples of exogenous agents:
glucoCEST: The property of cancer
cells to preferentially absorb glucose is known as the Warburg Effect. Enhanced
CEST-MRI of tumors was reported following administration of glucose and of its
analogues 2-deoxy-D-glucose, 2-fluoro-2-deoxy-D-glucose, and of
3-O-methyl-D-glucose [32-36];
acidoCEST: In addition to tissue pH measurements
using endogenous agents such as APT of proteins [ 21], gluCEST of glutamate [19,
21] and crCEST of creatine [27], the use
of exogenous agents was developed for the determination of extra-cellular pH [37-45].
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