Variable delay multi-pulse train for fast chemical exchange saturation transfer and relayed-nuclear overhauser enhancement MRI

Xu, Jiadi; Yadav, Nirbhay N.; Bar‐Shir, Amnon; Jones, Craig K.; Chan, Kannie W. Y.; Zhang, Jiangyang; Walczak, Piotr; McMahon, Michael T.; Zijl, Peter C.M. van

doi:10.1002/mrm.24850

Cited by 117 publications

(194 citation statements)

References 79 publications

(133 reference statements)

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“…While we have concentrated on the performance of the IM-SHY scaffold using continuous wave saturation transfer preparation, the measurements included do not represent the performance of these compounds using pulsed exchange transfer methods such as two frequency irradiation [20] , CERT [21] , Frequency labeled EXchange transfer (FLEX) [22] or Variable Delay Multiple Pulse (VDMP) transfer [23] as these sequences are still under development at 3T. The use of a limited series of short selective high-power pulses has advantages for detecting rapidly exchanging compounds [7d] as recently demonstrated using FLEX on a paraCEST agent with a water k ex of 19,000 Hz.…”

Section: Resultsmentioning

confidence: 99%

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

Yang

Yadav

Song

et al. 2014

Chemistry A European J

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We characterize what the optimal exchange properties are for CEST contrast agents on 3T clinical scanners using CW saturation transfer, and demonstrate that the exchangeable protons in phenols can be tuned to reach these criteria through proper ring substitution. Systematic modification allows the chemical shift of the exchangeable protons to be positioned between 4.8 ppm to 12 ppm from water and enables adjustment of the proton exchange rate to maximize CEST contrast at these shifts. In particular, 44 hydrogen-bonded phenols are investigated for their potential as CEST MRI contrast agents and the stereoelectronic effects on their CEST properties summarized. Furthermore, we identify a pair of compounds, 2,5-dihydroxyterephthalic acid (42) and 4,6-dihydroxyisophthalic acid (43), which produce the highest sensitivity through incorporating two exchangeable protons per ring.

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Section: Resultsmentioning

confidence: 99%

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

Yang

Yadav

Song

et al. 2014

Chemistry A European J

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“…These transfer rate estimates are in close agreement with consensus literature values that have been made under similar conditions. [18] Tellingly however, the experimental iso-transfer curves show systematic deviations from the general shape predicted by Bloch simulation. The APT peak (black diamonds) in particular has a significantly flatter profile than any of the surrounding simulated iso-transfer contours.…”

Section: Resultsmentioning

confidence: 95%

Transfer Rate Edited experiment for the selective detection of Chemical Exchange via Saturation Transfer (TRE-CEST)

Friedman

Xia

Regatte

et al. 2015

Journal of Magnetic Resonance

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Chemical Exchange Saturation Transfer (CEST) magnetic resonance experiments have become valuable tools in magnetic resonance for the detection of low concentration solutes with far greater sensitivity than direct detection methods. Accurate measures of rates of chemical exchange provided by CEST are of particular interest to biomedical imaging communities where variations in chemical exchange can be related to subtle variations in biomarker concentration, temperature and pH within tissue using MRI. Despite their name, however, traditional CEST methods are not truly selective for chemical exchange and instead detect all forms of magnetization transfer including through-space NOE. This ambiguity crowds CEST spectra and greatly complicates subsequent data analysis. We have developed a Transfer Rate Edited CEST experiment (TRE-CEST) that uses two different types of solute labeling in order to selectively amplify signals of rapidly exchanging proton species while simultaneously suppressing ‘slower’ NOE-dominated magnetization transfer processes. This approach is demonstrated in the context of both NMR and MRI, where it is used to detect the labile amide protons of proteins undergoing chemical exchange (at rates ≥ 30 s−1) while simultaneously eliminating signals originating from slower (~ 5 s−1) NOE-mediated magnetization transfer processes. TRE-CEST greatly expands the utility of CEST experiments in complex systems, and in-vivo, in particular, where it is expected to improve the quantification of chemical exchange and magnetization transfer rates while enabling new forms of imaging contrast.

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“…Thus, both long and short T 2 spin systems and slow and fast transferring components contribute to the MTR asym , the relative magnitude of which depends on the B 1 field used. 53,69,75 At low B 1 , slow exchanging protons (<100 Hz, mainly amide protons) and rNOEs from mobile MMs dominate. As B 1 is increased, the comparatively faster exchanging amide, amine, imino, and hydroxyl protons and the partially asymmetric conventional MTC effect become dominant.…”

Section: In Vivo Cest Spectrummentioning

confidence: 99%

“…The VDMP (variable-delay multi-pulse) approach of Xu et al 69 exploits the differences in transfer time between different mechanisms to select out the ones of interest. Figure 9(a) shows this principle based on Bloch simulations for MTC, rNOE, amide protons, and amine protons for the pulse sequence in Figure 6(b1) with 16 RF pulses and multiple delay times.…”

Section: Saturation-based Editing Sequencesmentioning

confidence: 99%

“…This approach can be employed with a high B 1 and a limited number of pulses (16-64, B 1 = 3.4 μT, t sat = 20 ms) to provide a sufficient CEST effect. 69,73 The RF pulses serve both as a relaxation filter for the interfering saturation contributions as well as an exchange rate filter for the CEST contributions. This enables application to many different types of protons.…”

Section: Exchange Transfer Sequences Employing Excitationmentioning

confidence: 99%

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Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

Zijl

Sehgal

2016

eMagRes

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Proton magnetic resonance spectroscopy ( 1 H MRS) of biological systems has higher specificity than MRI because resonances of multiple metabolites can be distinguished, reflecting chemistry and physiology in situ. Unfortunately, this approach has very low sensitivity as the metabolites are typically at millimolar concentrations compared to the molar signal strength of water-based MRI. As a consequence, even though 1 H MRS is a powerful and common research tool, its inroad into daily clinical practice has been limited. Until very recently, 1 H MRS applications have focused on the resonances upfield (i.e., at lower frequency) of the water resonance. This article deals with protons that are generally not observed in a typical water-suppressed spectrum, namely, the exchangeable protons found predominantly downfield from water. These can usually be detected by MRS only if the transfer of water proton saturation (established during water suppression) is not a confounding factor, or by using water exchange (WEX) spectroscopy, in which RF labeling of the water protons is transferred to the exchangeable protons and subsequently detected. More importantly, it has recently become clear that the presence of such exchangeable protons on low concentration solute molecules can be detected via the water signal by RF labeling of these protons and subsequent transfer of this label to water protons. This process, leading to saturation of the water signal and enhancement of the effect through repeated exchange, can be used for the imaging of metabolite signals or exchangeable-proton-based contrast agents with enhanced sensitivity. This has given rise to the field of chemical exchange saturation transfer (CEST) MRI, which has greatly increased the potential for translating spectroscopic methods to the clinic. Examples include the measurement of pH, temperature, and enzyme activity as well as detection of cellular metabolites, ions, and proteins and peptides. In addition, bio-organic compounds can now be used for contrast agents, cell and nanoparticle labeling, and reporter genes.

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Variable delay multi-pulse train for fast chemical exchange saturation transfer and relayed-nuclear overhauser enhancement MRI

Cited by 117 publications

References 79 publications

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

Transfer Rate Edited experiment for the selective detection of Chemical Exchange via Saturation Transfer (TRE-CEST)

Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

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