CEST and PARACEST MR contrast agents
GE Global Research Center, Niskayuna, NY, USA.Acta Radiologica (Impact Factor: 1.6). 10/2010; 51(8):910-23. DOI: 10.3109/02841851.2010.502126
In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and speculate about the next steps that may be taken towards the demonstration of CEST MR imaging in clinical applications.
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- "Lauffer briefly discussed the properties of copper as a platform for the design of imaging agents 25 years ago, deeming it unsuitable for use due to its poor relaxivity (Lauffer 1987). However, with the advent of better imaging software, access to higher field strengths, more sophisticated pulse sequences and the emergence of chemical exchange saturation transfer (CEST) as a relaxation mechanism, the need for metals with such high relaxivity may be coming to an end (De Leon- Rodriguez et al. 2009; Aime et al. 2009; Hancu et al. 2010; Sherry and Wu 2013). The design of MRI contrast agents has developed significantly over the Table 1 The properties of gadolinium and certain first row transition metal species key to their ability to perform as contrast agents (Tobe 1972; Weast 1980) No. unpaired electrons and relevant oxidation state "
ABSTRACT: The study reports an advance in designing copper-based redox sensing MRI contrast agents. Although the data demonstrate that copper(II) complexes are not able to compete with lanthanoids species in terms of contrast, the redox-dependent switch between diamagnetic copper(I) and paramagnetic copper(II) yields a novel redox-sensitive contrast moiety with potential for reversibility.
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- "Chemical exchange saturation transfer (CEST) (Aime et al., 2009; Ali et al., 2009; Guivel-Scharen et al., 1998; Hancu et al., 2010; Sherry and Woods, 2008; van Zijl and Yadav, 2011; Ward et al., 2000; Zhou and van Zijl, 2006) is a type of magnetization transfer (MT) that employs the transfer of saturation from low concentration exogenous or endogenous pools of exchangeable protons to the bulk water proton pool. These include amide or imino (NH) protons, amine (NH 2 ) protons , and hydroxyl (OH) protons. "
ABSTRACT: Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus an relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.
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ABSTRACT: Magnetic resonance has an established role in investigations on the evolution of stroke and the assessment of therapeutic strategies in experimental animals. Here we show that the technique has also an important place for the study of stem cell-mediated regenerative therapies after stroke. We review the literature by bridging from the methodological aspects of stem cell labeling via grafting and monitoring of cell dynamics after implantation into the brain all the way to MRI's role in analyzing the stem cell-mediated functional improvement. Thus, we have aimed at a view combining the focus on the monitoring of the cell activities with the aspect of lesion evolution while including also the essence of a potential functional improvement by the implantation of stem cells following stroke.
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