13C MRI of hyperpolarized pyruvate at 120 µT.

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth's magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth's magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years.

LIGHT-SABRE Hyperpolarizes 1-13C-Pyruvate Continuously without Magnetic Field Cycling.

Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at the 121 µT magnetic field (approximately twice Earth's field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the J-coupling network of reversibly exchanging Ir-complexes. Using ∼100% parahydrogen at ambient pressure, we polarized 51 mM 1-13C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at -8 °C, where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse 13C magnetization along the applied magnetic field, 13C z-magnetization along the main field B 0, and 13C-1H zz-spin order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from 1H-13C J-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz and at -8 °C.

Coherent Evolution of Signal Amplification by Reversible Exchange in Two Alternating Fields (alt-SABRE).

Parahydrogen (pH2 ) is a convenient and cost-efficient source of spin order to enhance the magnetic resonance signal. Previous work showed that transient interaction of pH2 with a metal organic complex in a signal amplification by reversible exchange (SABRE) experiment enabled more than 10 % polarization for some 15 N molecules. Here, we analyzed a variant of SABRE, consisting of a magnetic field alternating between a low field of ∼1 µT, where polarization transfer is expected to take place, and a higher field >50 µT (alt-SABRE). These magnetic fields affected the amplitude and frequency of polarization transfer. Deviation of a lower magnetic field from a "perfect" condition of level anti-crossing increases the frequency of polarization transfer that can be exploited for polarization of short-lived transient SABRE complexes. Moreover, the coherences responsible for polarization transfer at a lower field persisted during magnetic field variation and continued their spin evolution at higher field with a frequency of 2.5 kHz at 54 µT. The latter should be taken into consideration for an efficient alt-SABRE. Theoretical and experimental findings were exemplified with Iridium N-heterocyclic carbene SABRE complex and 15 N-acetonitrole, where a 30 % higher 15 N polarization with alt-SABRE compared to common SABRE was reached.

Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol.

INTRODUCTION: Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT. METHODS AND ANALYSIS: DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0-2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0-2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment. ETHICS AND DISSEMINATION: The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT03969511.