No abstract

Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost 13 C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) 13 C-labelled precursors with a time resolution of seconds. The exogenous administration of the metabolite L-lactate was shown to decrease lesion size and ameliorate neurological outcome in preclinical studies in rodent stroke models, as well as influencing brain metabolism in clinical pilot studies of acute brain injury patients. The aim of this study was to demonstrate the feasibility of measuring HP [1-13 C] L-lactate metabolism in real-time in the mouse brain after ischaemic stroke when administered after reperfusion at a therapeutic dose. We showed a rapid, time-after-reperfusion-dependent conversion of [1-13 C] L-lactate to [1-13 c] pyruvate and [ 13 c] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-13 C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.

Low throughput is one of dissolution Dynamic Nuclear Polarization (dDNP) main shortcomings. Especially for clinical and preclinical applications, where direct 13C nuclei polarization is usually pursued, it takes hours to generate one single hyperpolarized (HP) sample. Being able to hyperpolarize more samples at once represents a clear advantage and can expand the range and complexity of the applications. In this work, we present the design and performance of a highly versatile and customizable dDNP cryogenic probe, herein adapted to a 5 T “wet” preclinical polarizer, that can accommodate up to three samples at once and, most importantly, it is capable of monitoring the solid-state spin dynamics of each sample separately, regardless of the kind of radical used and the nuclear species of interest. Within 30 min, the system was able to dispense three HP solutions with high repeatability across the channels (30.0 ± 1.2% carbon polarization for [1-13C]pyruvic acid doped with trityl radical). Moreover, we tested multi-nucleus NMR capability by polarizing and monitoring simultaneously 13C, 1H and 129Xe. Finally, we implemented [1-13C]lactate/[1-13C]pyruvate polarization and back-to-back dissolution and injection in a healthy mouse model to perform multiple-substrate HP Magnetic Resonance Spectroscopy (MRS) at 14.1 T.

Simultaneous scalp electroencephalography and functional magnetic resonance imaging (EEG-fMRI) enable noninvasive assessment of brain function with high spatial and temporal resolution. However, at ultra-high field, the data quality of both modalities is degraded by mutual interactions. Here, we thoroughly investigated the radiofrequency (RF) shielding artifact of a state-of-the-art EEG-fMRI setup, at 7 T, and design a practical solution to limit this issue. Methods: Electromagnetic field simulations and MR measurements assessed the shielding effect of the EEG setup, more specifically the EEG wiring. The effectiveness of segmenting the wiring with resistors to reduce the transmit field disruption was evaluated on a wire-only EEG model and a simulation model of the EEG cap. Results:The EEG wiring was found to exert a dominant effect on the disruption of the transmit field, whose intensity varied periodically as a function of the wire length. Breaking the electrical continuity of the EEG wires into segments shorter than one quarter RF wavelength in air (25 cm at 7 T) reduced significantly the RF shielding artifacts. Simulations of the EEG cap with segmented wires indicated similar improvements for a moderate increase of the power deposition. Conclusion:We demonstrated that segmenting the EEG wiring into shorter lengths using commercially available nonmagnetic resistors is effective at reducing RF shielding artifacts in simultaneous EEG-fMRI. This prevents the formation of RF-induced standing waves, without substantial specific absorption rate (SAR) penalties, and thereby enables benefiting from the functional sensitivity boosts achievable at ultra-high field.

No abstract

Dissolution Dynamic Nuclear Polarization (dDNP) is the most versatile hyperpolarization technique to enhance NMR sensitivity in the liquid state. The unprecedented signal enhancement is the key for a large range of applications spanning from fast chemical reaction monitoring to metabolism investigation in real time. Unfortunately, this exceptional time resolution does not come without a price. Low throughput is one of dDNP main shortcomings. Especially for clinical and preclinical applications, where direct 13C nuclei polarization is usually pursued, it takes hours to generate one single hyperpolarized (HP) sample. Therefore, being able to hyperpolarize more samples at once represents a clear advantage and can expand the range and complexity of the applications. Some clinical and preclinical systems are equipped with a multi-sample option. Nevertheless, the solid-state NMR detection is far from optimal, not being sample selective or requiring the displacement of the sample to acquire and monitor its signal. In this work, we present the design and performance of a highly versatile and customizable dDNP cryogenic probe, herein adapted to a 5 T “wet” preclinical polarizer, that can not only accommodate up to three Custom Fluid Paths (CFPs), but it is also capable of monitoring the solid-state dynamics of each sample separately, thanks to dedicated pseudo-Alderman-Grant coils and multi-nuclei parallel Nuclear Magnetic Resonance (NMR) acquisition on three distinct channels. Within 30 min, the system was able to dispense three HP solutions with high repeatability across the channels (30.0 ± 1.2% carbon polarization for [1-13C]pyruvic acid doped with trityl radical). Moreover, we tested multi-nucleus NMR capability by polarizing and monitoring simultaneously 13C, 1H and 129Xe. Finally, we implemented [1-13C]lactate/[1-13C]pyruvate polarization and back-to-back dissolution and injection in a healthy mouse model to perform multiple-substrate HP Magnetic Resonance Spectroscopy (MRS) at 14.1 T.

Dissolution DNP (dDNP) is an alternative for hyperpolarizing 129Xe to the well acknowledged method spin exchange optical pumping (SEOP). As opposed to SEOP, DNP takes place in the solid state at very low temperatures. Therefore, it can potentially produce a large volume of hyperpolarized gas after dissolution. In this study, by implementing a new way of preparing the sample, we ease the overall process and establish a superior incorporation of the gas atoms into the solvent. Additionally, due to a surprisingly short radical electron T1, we show that a higher polarization was achieved by applying microwave frequency modulation.

The present work describes a quantitative analysis of lactate 13C-labeling pattern following the metabolism of hyperpolarized [2H7,U-13C6]-D-glucose. This lactate production results from 12 biochemical steps including glucose transport, 10 enzymatic steps of glycolysis, and LDH mediated pyruvate-to-lactate conversion. The 3-compartment model description was found a good compromise to interpret the hyperpolarized metabolic curves. This demonstrates the potential of hyperpolarized [2H7, U-13C6]-D-glucose as a new biochemical probe for brain energy metabolism.