NMR Hyperpolarization Techniques of Gases

Barskiy, Danila A.; Coffey, Aaron M.; Nikolaou, Panayiotis; Mikhaylov, Dmitry M.; Goodson, Boyd M.; Branca, Rosa T.; Lu, George J.; Shapiro, Mikhail G.; Telkki, Ville‐Veikko; Живонитко, Владимир В.; Koptyug, Igor V.; Salnikov, Oleg G.; Kovtunov, Kirill V.; Bukhtiyarov, Valerii I.; Rosen, Matthew S.; Barlow, Michael J.; Safavi, Shahideh; Hall, Ian P.; Schröder, Leif; Chekmenev, Eduard Y.

doi:10.1002/chem.201604827

Cited by 20 publications

(27 citation statements)

References 148 publications

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“…Hyperpolarized 129 Xe-MRI is an active area of molecular imaging research, which is currently mainly performed in vitro with pure contrast agents or labeled cells 18 , 19 , while in vivo techniques are being developed 12 , 13 . This protocol describes the imaging of GVs using hyperpolarized 129 Xe MRI in vitro , as previously done with purified GVs, GV-expressing cells and GV-labeled cells 11 .…”

Section: Experimental Designmentioning

confidence: 99%

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Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

et al. 2017

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Gas vesicles are a unique class of gas-filled protein nanostructures whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and magnetic resonance imaging (MRI), detectable at sub-nanomolar concentrations. Here we provide a protocol for isolating gas vesicles from native and heterologous host organisms, functionalizing these nanostructures with moieties for targeting and fluorescence, characterizing their biophysical properties and imaging them using ultrasound and magnetic resonance imaging. Gas vesicles can be isolated from natural cyanobacterial and haloarchaeal host organisms or from E. coli expressing a heterologous gas vesicle gene cluster, and purified using buoyancy-assisted techniques. They can then be modified by replacing surface-bound proteins with engineered, heterologously expressed variants, or through chemical conjugation, resulting in altered mechanical, surface and targeting properties. Pressurized absorbance spectroscopy is used to characterize their mechanical properties, while dynamic light scattering and transmission electron microscopy are used to determine nanoparticle size and morphology, respectively. Gas vesicles can then be imaged with ultrasound in vitro and in vivo using pulse sequences optimized for their detection versus background. They can also be imaged with hyperpolarized xenon MRI using chemical exchange saturation transfer between gas vesicle-bound and dissolved xenon – a technique currently implemented in vitro. Taking 3–8 days to prepare, these genetically encodable nanostructures enable multi-modal, noninvasive biological imaging with high sensitivity and potential for molecular targeting.

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Section: Experimental Designmentioning

confidence: 99%

“…In addition, the distinct chemical shifts of GVs in different microbial species enable multiplexed imaging. HyperCEST is currently performed in vitro , but is advancing toward in vivo use 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

et al. 2017

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“…Likewise, MRI is capable of whole‐body imaging with spatial resolution on the order of 100 µm, and uses a variety of contrast mechanisms arising from nuclear spin behavior . Among these mechanisms, hyperpolarized MRI provides particularly high molecular sensitivity using nuclei, such as 129 Xe, prepared with nonequilibrium polarization several orders of magnitude higher than that available under equilibrium conditions . Hyperpolarized 129 Xe can be administered through inhalation or injection for in vivo imaging.…”

Section: Introductionmentioning

confidence: 99%

Recombinantly expressed gas vesicles as nanoscale contrast agents for ultrasound and hyperpolarized MRI

Farhadi

Kunth

et al. 2018

AIChE Journal

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Ultrasound and hyperpolarized magnetic resonance imaging enable the visualization of biological processes in deep tissues. However, few molecular contrast agents are available to connect these modalities to specific aspects of biological function. We recently discovered that a unique class of gas-filled protein nanostructures known as gas vesicles could serve as nanoscale molecular reporters for these modalities. However, the need to produce these nanostructures via expression in specialized cultures of cyanobacteria or haloarchaea limits their broader adoption by other laboratories and hinders genetic engineering of their properties. Here, we describe recombinant expression and purification of Bacillus megaterium gas vesicles using a common laboratory strain of Escherichia coli, and characterize the physical, acoustic and magnetic resonance properties of these nanostructures. Recombinantly expressed gas vesicles produce ultrasound and hyperpolarized 129Xe MRI contrast at sub-nanomolar concentrations, thus validating a simple platform for their production and engineering.

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“…This low polarization results in overall MRI signals approximately 10 5 times weaker than they could be if all the available spins aligned with the applied magnetic field. This limitation can be overcome with hyperpolarization – an advanced technique in which nuclei are prepared via physical methods in a state of non-equilibrium polarization that is up to 10,000-fold stronger than baseline 33 . Hyperpolarized nuclei such as the noble gas 129 Xe can then be delivered to the body by inhalation to be imaged during their polarization half-life of a few seconds.…”

Section: Biomolecular Tools For Magnetic Resonance Imagingmentioning

confidence: 99%

Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

et al. 2017

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Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function – based on fluorescent or light-controlled proteins – work best in cultured cells, transparent model species or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for actuation. These capabilities are widely used in clinical techniques such as diagnostic ultrasound, magnetic resonance imaging, focused ultrasound ablation and magnetic particle hyperthermia. Each of these modalities offers spatial and temporal precision that could be used to study a multitude of cellular processes in vivo. However, connecting these techniques to cellular functions such as gene expression, proliferation, migration and signaling requires the development of new biochemical tools that can interact with sound waves and magnetic fields as optogenetic tools interact with photons. Here, we discuss the exciting challenges this poses for biomolecular engineering, and provide examples of recent advances pointing the way to greater depth in in vivo cell biology.

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NMR Hyperpolarization Techniques of Gases

Cited by 20 publications

References 148 publications

Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

Recombinantly expressed gas vesicles as nanoscale contrast agents for ultrasound and hyperpolarized MRI

Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

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