On-resonance low B1 pulses for imaging of the effects of PARACEST agents

Vinogradov, Elena; Zhang, Shanrong; Lubag, Angelo; Balschi, James A.; Sherry, A. Dean; Lenkinski, Robert E.

doi:10.1016/j.jmr.2005.05.016

Cited by 51 publications

(66 citation statements)

References 34 publications

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“…Consistent with a previous study (24), RF pulse power within the range of 2.5-14 T did not affect the OPARACHEE sensitivity in the absence or presence of macromolecules for a given pulse duration. These simulated results were also verified experimentally (data not shown).…”

Section: Resultssupporting

confidence: 90%

“…The power (265 Hz ϭ 6.35 T) and the duration of the RF pulse (0.48 sec) used for the simulations were the values used for the in vitro experiments described below. The T 1 and T 2 relaxation time constants and exchange rates associated with the PARACEST agent and the macromolecule pools were estimated from the literature (24,27), and the T 1 and the T 2 of bulk water were estimated using the standard inversion recovery method and CurrPurcell-Meiboom-Gill method, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Though dysprosium-, thulium (Tm 3ϩ )-, and ytterbium-based PARACEST agents have bound water chemical shifts beyond the MT effect range, the fast proton exchange between the bound water of these compounds and the bulk water results in an undetectable CEST signal within specific absorption rate power limits. However, the irradiation of bulk water (on-resonance) in solutions with fast proton exchange between bound water and bulk water may also produce contrast due to chemical exchange (24).…”

mentioning

confidence: 99%

“…The proton exchange between the bound water of PARACEST agents and bulk water in solution following on-resonance excitation using a WALTZ-16 pulse train (26) has been thoroughly modeled by Vinogradov et al (24) for a two-pool system based on the modified Bloch equations with exchange terms. The effects of relaxation time, agent concentration, frequency offset, and irradiation power were investigated.…”

mentioning

confidence: 99%

“…The effects of relaxation time, agent concentration, frequency offset, and irradiation power were investigated. However, the model proposed by Vinogradov et al (24) is not directly applicable in vivo due to the inherent MT effect from macromolecule-bound protons in biologic systems. Recently, Vinogradov et al (25) have observed the OPARACHEE effect in mouse kidney.…”

mentioning

confidence: 99%

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Optimized MRI contrast for on‐resonance proton exchange processes of PARACEST agents in biological systems

Suchý

Jones

et al. 2009

Magnetic Resonance in Med

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Image contrast associated with paramagnetic chemical exchange saturation transfer agents can be generated by off-resonance irradiation of agent-bound water or amide protons or on-resonance irradiation of bulk water. Previously, a four-pool model was developed to describe an in vivo system. The model incorporated the magnetization transfer effect from macromolecules when using off-resonance irradiation. In the current study, this four-pool model is modified to describe the in vivo system when using on-resonance irradiation. The influences of pulse power, pulse duration, the chemical shift of bound water, the proton exchange rate between bulk water and bound water, and agent concentration on the on-resonance paramagnetic agent chemical exchange effects were simulated using a WALTZ-16 pulse train in the absence and presence of the macromolecule pool. The results demonstrated that while contrast increases with pulse duration in aqueous solution, there is an optimal pulse duration that maximizes on-resonance paramagnetic agent chemical exchange effects contrast in vivo. Diamagnetic and paramagnetic chemical exchange saturation transfer (PARACEST) (1-12) agents have many possible medical and biologic applications, including the measurement of tissue pH based on the pH dependence of the exchange rate of amide protons with bulk water protons (13-15), the measurement of tissue temperature using the linear dependence of the bound water chemical shift on temperature (16,17), enzymatic activity (18), and metabolite levels (19-21). The CEST detection sensitivity (or CEST effect) is defined as the change in the bulk water signal intensity of the agent solution following irradiation of the exchangeable protons. The PARACEST effect and the chemical shift of bound protons can be modified using different metals in the lanthanide series or ligands (22). Currently, the most efficient PARACEST agents are europium (Eu 3ϩ ) based, with a bound water chemical shift around 45 parts per million (ppm) and visible CEST contrast from millimolar concentrations.Despite the large chemical shift of the bound water and amide protons associated with PARACEST agents, the relatively high saturation power needed for in vivo PARAC-EST imaging results in the simultaneous observation of inherent magnetization transfer (MT) from macromolecule-bound protons (17,23). Though dysprosium-, thulium (Tm 3ϩ )-, and ytterbium-based PARACEST agents have bound water chemical shifts beyond the MT effect range, the fast proton exchange between the bound water of these compounds and the bulk water results in an undetectable CEST signal within specific absorption rate power limits. However, the irradiation of bulk water (on-resonance) in solutions with fast proton exchange between bound water and bulk water may also produce contrast due to chemical exchange (24).The detected effect of a PARACEST agent based on the radiofrequency (RF) excitation of bulk water was previously described as the on-resonance paramagnetic agent chemical exchange effect (OPARACHEE) to differe...

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Optimized MRI contrast for on‐resonance proton exchange processes of PARACEST agents in biological systems

Suchý

Jones

et al. 2009

Magnetic Resonance in Med

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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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