Molecular Imaging Using a Targeted Magnetic Resonance Hyperpolarized Biosensor

Schröder, Leif; Lowery, Thomas J.; Hilty, Christian; Wemmer, David E.; Pines, Alexander

doi:10.1126/science.1131847

Cited by 436 publications

(430 citation statements)

References 20 publications

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“…Whereas direct detection requires high host concentrations, selective RF saturation is very efficient in causing a loss in the abundant free Xe signal. The 5 combination of hyperpolarized xenon and detection with CEST amplification (Hyper-CEST 9 ) allows such host structures to be detected at concentrations at the pM to nM level. The typical Hyper-CEST agent has a hydrophobic xenon binding site in a cage-like molecule that can be functionalized to bind molecular targets.…”

mentioning

confidence: 99%

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Kunth

Witte

et al. 2018

ACS Nano

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Signal amplification strategies are critical for overcoming the intrinsically poor sensitivity of nuclear magnetic resonance (NMR) reporters in noninvasive molecular detection. A mechanism widely used for signal enhancement is chemical exchange saturation transfer (CEST) of nuclei between a dilute sensing pool and an abundant detection pool. However, the dependence of CEST amplification on the relative size of these spin pools confounds quantitative molecular detection with a larger detection pool typically making saturation transfer less efficient. Here we show that a recently discovered class of genetically encoded nanoscale reporters for 129 Xe magnetic resonance overcomes this fundamental limitation through an elastic binding capacity for NMR-active nuclei. This approach pairs high signal amplification from hyperpolarized spins with ideal, self-adjusting saturation transfer behavior as the overall spin ensemble changes in size. These reporters are based on gas vesicles, i.e., microbe-derived, gas-filled protein nanostructures. We show that the xenon fraction that partitions into gas vesicles follows the ideal gas law, allowing the signal transfer under hyperpolarized xenon chemical exchange saturation transfer (Hyper-CEST) imaging to scale linearly with the total xenon ensemble. This conceptually distinct elastic response allows the production of quantitative signal contrast that is robust to variability in the concentration of xenon, enabling virtually unlimited improvement in absolute contrast with increased xenon delivery, and establishing a unique principle of operation for contrast agent development in emerging biochemical and in vivo applications of hyperpolarized NMR and magnetic resonance imaging.

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confidence: 99%

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Kunth

Witte

et al. 2018

ACS Nano

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“…The development of xenon-based contrast agents has been largely enabled by the development and application of the Hyper-CEST acquisition method (12). Hyper-CEST is a technique which combines the advantages of hyperpolarized xenon gas (hp-Xe) (13) with the chemical exchange saturation transfer (CEST) detection method (14,15) to significantly enhance signal to noise.…”

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confidence: 99%

Development of an antibody-based, modular biosensor for¹²⁹Xe NMR molecular imaging of cells at nanomolar concentrations

Rose

Witte

Rossella

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

104

119

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Significance The field of xenon magnetic resonance imaging (MRI) is moving closer to the development of targeted xenon biosensors for in vivo applications. It is motivated by a ca. 10 8 -fold improved sensitivity compared with conventional proton MRI. This has been enabled by significant improvements to hardware (xenon polarizer design) and sensitivity (through the hyperpolarized 129 Xe chemical exchange saturation transfer technique). In this paper, we capitalize on these improvements by demonstrating targeted xenon imaging on cells using a modular xenon biosensor. With this method, we can detect target cells with as little as 20 nM of our xenon contrast agent. Imaging of such low levels of cell-specific xenon hosts is unprecedented and reinforces the potential of xenon–cryptophane biosensors for molecular imaging applications.

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“…Among many formidable challenges, efficient nuclear spin hyperpolarization and manipulation at room temperature (RT) are essential to the success of future solid-state quantum computation using nuclear spin qubits [8][9][10][11][12][13][14][15][16] , as well as in highly sensitive magnetic resonance imaging (MRI) 17,18 . The most common approach employed so far in achieving nuclear spin hyperpolarization is based on dynamic nuclear polarization (DNP).…”

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Efficient room-temperature nuclear spin hyperpolarization of a defect atom in a semiconductor

et al. 2013

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Nuclear spin hyperpolarization is essential to future solid-state quantum computation using nuclear spin qubits and in highly sensitive magnetic resonance imaging. Though efficient dynamic nuclear polarization in semiconductors has been demonstrated at low temperatures for decades, its realization at room temperature is largely lacking. Here we demonstrate that a combined effect of efficient spin-dependent recombination and hyperfine coupling can facilitate strong dynamic nuclear polarization of a defect atom in a semiconductor at room temperature. We provide direct evidence that a sizeable nuclear field (B150 Gauss) and nuclear spin polarization (B15%) sensed by conduction electrons in GaNAs originates from dynamic nuclear polarization of a Ga interstitial defect. We further show that the dynamic nuclear polarization process is remarkably fast and is completed in o5 ms at room temperature. The proposed new concept could pave a way to overcome a major obstacle in achieving strong dynamic nuclear polarization at room temperature, desirable for practical device applications.

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Molecular Imaging Using a Targeted Magnetic Resonance Hyperpolarized Biosensor

Cited by 436 publications

References 20 publications

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Development of an antibody-based, modular biosensor for¹²⁹Xe NMR molecular imaging of cells at nanomolar concentrations

Efficient room-temperature nuclear spin hyperpolarization of a defect atom in a semiconductor

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Molecular Imaging Using a Targeted Magnetic Resonance Hyperpolarized Biosensor

Cited by 436 publications

References 20 publications

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Development of an antibody-based, modular biosensor for129Xe NMR molecular imaging of cells at nanomolar concentrations

Efficient room-temperature nuclear spin hyperpolarization of a defect atom in a semiconductor

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Development of an antibody-based, modular biosensor for¹²⁹Xe NMR molecular imaging of cells at nanomolar concentrations