SQUID-based ultralow-field MRI of a hyperpolarized material using signal amplification by reversible exchange

Lee, Seong-Joo; Jeong, Keunhong; Shim, Jae-Hyeok; Lee, Hyun Joon; Min, Sein; Chae, Heelim; Namgoong, Sung Keon; Kim, Ki Woong

doi:10.1038/s41598-019-48827-5

Cited by 25 publications

(17 citation statements)

References 47 publications

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“…The magnetic field generated by the controlled current was measured using a Lakeshore Gaussmeter. Favipiravir (5 mg, 3.1 × 10 −2 mmol) and the pre-catalyst ([Ir(IMes)(COD)Cl], 2 mg, 3.1 × 10 −3 mmol) were dissolved in CD 3 OD (900 μL) 43 . Chloroquine and hydroxychloroquine samples for hyperpolarization were prepared by mixing a solution of the substrate (3.9 × 10 −3 mmol) and [Ir(IMes)(COD)Cl] (2 mg, 3.1 × 10 −3 mmol) in CD 3 OD (900 μL).…”

Section: Methodsmentioning

confidence: 99%

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Jeong

Min

Chae

et al. 2020

Sci Rep

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Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies. Coronavirus pneumonia (COVID-19) is a serious respiratory infectious disease that has emerged recently. Patients with coronavirus infection demonstrate fever with body temperature exceeding 38 °C, and symptoms, such as dry cough, fatigue, dyspnea, difficulty in breathing, and frosted glass-like symptoms in the lungs 1. The disease is known to be highly transmittable without the occurrence of severe symptoms. The number of cases has reached over tens of millions worldwide. To overcome this pandemic, many researchers have started working on developing a vaccine. However, ongoing vaccine developments are estimated to take over a year before becoming available for public use. As a result, the global clinical community is attempting to repurpose existing drugs to tackle the COVID-19 crisis. Recently, several drugs that can inhibit specific functions of the virus have been proposed and tested as part of the latest clinical treatment approaches. These drugs include chloroquine and hydroxychloroquine. Although the role of these drugs in the treatment of COVID-19 is controversial, hydroxychloroquine is more soluble than chloroquine and produces relatively less toxic metabolites 2-4. Although chloroquine (7-chloro-4-(4-diethylamino-1-methylbutylamino)-quinoline) and hydroxychloroquine (2-[4-[(7-chloroquinolin-4-yl)amino]pentylethylamino]ethanol), which have been in clinical usage for the last seventy years, are drugs for the treatment of autoimmune disease, they are also used as antimalarial drugs. These compounds have recently been reported as potential broad-spectrum antiviral drugs for COVID-19 5 ; however, their benefits against COVID-19 are controversial, with no evident effect on hospitalized patients 6. From a molecular perspective, the...

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Section: Methodsmentioning

confidence: 99%

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Jeong

Min

Chae

et al. 2020

Sci Rep

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“…The schematic image of a common sensing element of the dc SQUID magnetometer is presented in Figure 3. These sensors are widely used in the detection of low magnetic fields starting from the magnetic properties of materials to ultra low-field sensing in magnetic resonance imaging [52,53]. The sensing element of the dc SQUID magnetometer can be presented as a semiconducting loop with two separated parallel Josephson junctions.…”

Section: Squid Magnetometersmentioning

confidence: 99%

Ultrasensitive Magnetic Field Sensors for Biomedical Applications

Murzin

Mapps

Levada

et al. 2020

Sensors

131

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The development of magnetic field sensors for biomedical applications primarily focuses on equivalent magnetic noise reduction or overall design improvement in order to make them smaller and cheaper while keeping the required values of a limit of detection. One of the cutting-edge topics today is the use of magnetic field sensors for applications such as magnetocardiography, magnetotomography, magnetomyography, magnetoneurography, or their application in point-of-care devices. This introductory review focuses on modern magnetic field sensors suitable for biomedicine applications from a physical point of view and provides an overview of recent studies in this field. Types of magnetic field sensors include direct current superconducting quantum interference devices, search coil, fluxgate, magnetoelectric, giant magneto-impedance, anisotropic/giant/tunneling magnetoresistance, optically pumped, cavity optomechanical, Hall effect, magnetoelastic, spin wave interferometry, and those based on the behavior of nitrogen-vacancy centers in the atomic lattice of diamond.

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“…We note that a similar approach was used by Hövner and co-workers to demonstrate continuous hyperpolarization and MRI using SABRE with Earth’s field detection [27,31]. In addition, SABRE hyperpolarization has been observed in low and ultra-low fields using standard detectors [32], superconducting quantum interference devices (SQUIDs) [33,34,35], and atomic magnetometers [36]. PHIP hyperpolarization has also been observed using in situ detection, where the polarization transfer and detection are both achieved in the mT regime [37,38].…”

Section: Introductionmentioning

confidence: 97%

In Situ SABRE Hyperpolarization with Earth’s Field NMR Detection

et al. 2019

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Hyperpolarization methods, which increase the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), have the potential to expand the range of applications of these powerful analytical techniques and to enable the use of smaller and cheaper devices. The signal amplification by reversible exchange (SABRE) method is of particular interest because it is relatively low-cost, straight-forward to implement, produces high-levels of renewable signal enhancement, and can be interfaced with low-cost and portable NMR detectors. In this work, we demonstrate an in situ approach to SABRE hyperpolarization that can be achieved using a simple, commercially-available Earth’s field NMR detector to provide 1H polarization levels of up to 3.3%. This corresponds to a signal enhancement over the Earth’s magnetic field by a factor of ε > 2 × 108. The key benefit of our approach is that it can be used to directly probe the polarization transfer process at the heart of the SABRE technique. In particular, we demonstrate the use of in situ hyperpolarization to observe the activation of the SABRE catalyst, the build-up of signal in the polarization transfer field (PTF), the dependence of the hyperpolarization level on the strength of the PTF, and the rate of decay of the hyperpolarization in the ultra-low-field regime.

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SQUID-based ultralow-field MRI of a hyperpolarized material using signal amplification by reversible exchange

Cited by 25 publications

References 47 publications

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Ultrasensitive Magnetic Field Sensors for Biomedical Applications

In Situ SABRE Hyperpolarization with Earth’s Field NMR Detection

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