Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors

Meldrum, Tyler; Bajaj, Vikram S.; Wemmer, David E.; Pines, Alexander

doi:10.1016/j.jmr.2011.06.027

Cited by 25 publications

(25 citation statements)

References 27 publications

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“…It has been shown that, compared with CW saturation, pulsed saturation can achieve comparable saturation efficiency at lower power, thus minimizing RF heating. 69 Recently, hyper-CEST data with CB[6] in whole blood was reported using prepulse train with a SAR of 0.025 W/kg, well below the FDA limit of 4 W/kg. 59 …”

Section: Discussionmentioning

confidence: 99%

An Expanded Palette of Xenon-129 NMR Biosensors

Wang

Dmochowski

2016

Acc. Chem. Res.

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ConspectusMolecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, by determining the location and relative concentration of specific molecules of interest. Proton-based magnetic resonance imaging (1H MRI) is nonionizing and provides good spatial resolution for clinical imaging but lacks sensitivity for imaging low-abundance (i.e., submicromolar) molecular markers of disease or environments with low proton densities. To address these limitations, hyperpolarized (hp) 129Xe NMR spectroscopy and MRI have emerged as attractive complementary methodologies. Hyperpolarized xenon is nontoxic and can be readily delivered to patients via inhalation or injection, and improved xenon hyperpolarization technology makes it feasible to image the lungs and brain for clinical applications.In order to target hp 129Xe to biomolecular targets of interest, the concept of “xenon biosensing” was first proposed by a Berkeley team in 2001. The development of xenon biosensors has since focused on modifying organic host molecules (e.g., cryptophanes) via diverse conjugation chemistries and has brought about numerous sensing applications including the detection of peptides, proteins, oligonucleotides, metal ions, chemical modifications, and enzyme activity. Moreover, the large (∼300 ppm) chemical shift window for hp 129Xe bound to host molecules in water makes possible the simultaneous identification of multiple species in solution, that is, multiplexing. Beyond hyperpolarization, a 106-fold signal enhancement can be achieved through a technique known as hyperpolarized 129Xe chemical exchange saturation transfer (hyper-CEST), which shows great potential to meet the sensitivity requirement in many applications.This Account highlights an expanded palette of hyper-CEST biosensors, which now includes cryptophane and cucurbit[6]uril (CB[6]) small-molecule hosts, as well as genetically encoded gas vesicles and single proteins. In 2015, we reported picomolar detection of commercially available CB[6] via hyper-CEST. Inspired by the versatile host–guest chemistry of CB[6], our lab and others developed “turn-on” strategies for CB[6]-hyper-CEST biosensing, demonstrating detection of protein analytes in complex media and specific chemical events. CB[6] is starting to be employed for in vivo imaging applications. We also recently determined that TEM-1 β-lactamase can function as a single-protein reporter for hyper-CEST and observed useful saturation contrast for β-lactamase expressed in bacterial and mammalian cells. These newly developed small-molecule and genetically encoded xenon biosensors offer significant potential to extend the scope of hp 129Xe toward molecular MRI.

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Section: Discussionmentioning

confidence: 99%

An Expanded Palette of Xenon-129 NMR Biosensors

Wang

Dmochowski

2016

Acc. Chem. Res.

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“…The exact field strength allowed is a complicated question, as SAR will also be affected by the choice of transmit coil and use of smaller transmit coils (108) or parallel transmit coils (109) can reduce the deposition of heat. However, in the case that the hardware doesn't allow sufficiently strong cw pulses for saturation, an alternative is to use a train of shaped pulses instead (110), often called pulsed-CEST MRI. A number of waveforms have been tested which were previously used in NMR spectroscopy and conventional MTC studies including: Fermi (96,111), e-burp (67,112), Gaussian (50,113), SEDUCE (110), d-SNOB (110), and Blackman-shaped inversion pulses (114).…”

Section: Introductionmentioning

confidence: 99%

“…Fig. 7 shows two alternative shapes which have been used previously, dSNOB (110) (Fig. 7d-f), and Fermi(96) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Nuts and bolts of chemical exchange saturation transfer MRI

et al. 2013

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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 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 detecting changes in their environment (e.g. pH, metabolites, etc) through MR contrast. Currently a large number of new imaging schemes and techniques have been developed to improve the temporal resolution and specificity and to correct the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the last decade have been summarized with the different imaging strategies and post-processing methods discussed from a practical point of view including describing their relative merits for detecting 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, Post-Processing, and also includes a brief Introduction section 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 choice of magnetic field, pulse sequence, saturation pulse, imaging scheme, and strategies to separate MT 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 improving CEST contrast maps.

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“…Recent studies demonstrated that, compared to a continuous wave, a band-selective saturation sequence based on multiple pulse inversion elements can yield saturation bandwidth tunable over a wide range, while inducing less RF power in the sample and therefore preventing RF tissue heating during imaging. 66 Thus, according to the remarks done in the previous Sections, the quest for a host molecule for which xenon exhibits a strong affinity -and still a high in-out exchange -is made important again. In this sense, so far cryptophanes seem to be the best candidates, as they could provide the higher contrast at low saturation strength.…”

Section: Future Directionsmentioning

confidence: 98%

¹²⁹Xe NMR-based sensors: biological applications and recent methods

Mari

Berthault

2017

Analyst

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aXenon is a first-rate sensor of biological events, due to its large polarizable electron cloud inducing significant modification of NMR parameters through slight changes in its local environment. The use of xenon as a sensor is of increasing interest for sensitive magnetic resonance imaging, since its signal can be enhanced by several orders of magnitude, mainly by spinexchange optical pumping. Furthermore xenon can be vectorized toward targets of interest by using functionalized host systems, enabling their detection at subnanomolar concentrations. Associated with a new generation of detection methods this gives rise to a powerful molecular imaging approach, where xenon can be delivered on purpose several times after introduction of the functionalized host system. IntroductionFrom simple photograph of the inside of the human body providing information on bone structure or form and abnormalities of various organs, molecular imaging now offers a dynamic view of biological processes occurring locally, witnessing for instance the presence of infectious cells or metabolic deregulations. The development of powerful imaging techniques is the key to early diagnosis of disease, best follow-up treatments and also biomedical research tools. These techniques developed particularly in the 21th century form part of the molecular imaging concept. Magnetic resonance imaging (MRI) is a good compromise to achieve molecular imaging in vivo in real time without any perturbative radiation. The major advantages of MRI are its potential high spatial resolution (25-100 µm), its low invasiveness, its harmlessness and the excellent tissue contrast it can provide. In this context, MRI complements and sometimes overruns other molecular imaging approaches by enabling monitoring of events at the cellular or even subcellular level. However, classical implementation of this technique suffers from low sensitivity due to the very low population differences between nuclear spin energy levels at Boltzmann equilibrium. Hyperpolarization techniques 1 that transiently increase the nuclear spin polarization of a very dilute agent by several orders of magnitude circumvent the MRI sensitivity problem. Among the species that can be spinhyperpolarized, xenon is of high interest, due to its exogenous nature (leading to the absence of background signal) and the fact that it can act as a spy of biological events without interfering with them. Moreover, it can be endlessly reloaded and simply removed from the sample since it is a gas at ambient temperature and pressure. Finally, owing to the high deformability of its large electron cloud xenon is deeply sensitive to its local environment and constitutes a perfect probe for various biological interactions. Soluble in most biological fluids, xenon can cross the plasma membrane in a few tens of milliseconds without losing its hyperpolarization. 2The initial applications of hyperpolarized xenon in biology were the anatomical imaging of the lung 3 and the investigation of hydrophobic binding pockets in proteins ...

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Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors

Cited by 25 publications

References 27 publications

An Expanded Palette of Xenon-129 NMR Biosensors

An Expanded Palette of Xenon-129 NMR Biosensors

Nuts and bolts of chemical exchange saturation transfer MRI

¹²⁹Xe NMR-based sensors: biological applications and recent methods

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Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors

Cited by 25 publications

References 27 publications

An Expanded Palette of Xenon-129 NMR Biosensors

An Expanded Palette of Xenon-129 NMR Biosensors

Nuts and bolts of chemical exchange saturation transfer MRI

129Xe NMR-based sensors: biological applications and recent methods

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¹²⁹Xe NMR-based sensors: biological applications and recent methods