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Lotte Bonde Bertelsen

Publications and source records attributed to Lotte Bonde Bertelsen.

3 recordsLinked to original sources

Stable electron-irradiated [1-$^{13}$C]alanine radicals for clinically viable metabolic imaging with Dynamic Nuclear Polarization

Dissolution Dynamic Nuclear Polarisation (dDNP) increases the sensitivity of magnetic resonance experiments by $>10^4$-fold, permitting isotopically-labelled molecules to be transiently visible in MRI scans. dDNP requires a source of unpaired electrons in contact with labelled nuclei, cooled to $\sim$1K, and spin-pumped into a given state by microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as UV irradiation, generate lower polarisation and require cryogenic transport. We present ultra-high-dose-rate electron irradiation as a novel alternative for generating non-persistent radicals in alanine/glycerol mixtures. These are stable for months at room temperature, quench spontaneously upon dissolution, are present in dose-dependent concentrations, and generate comparable nuclear polarisation to trityl radicals used clinically (20\%) through a novel mechanism. This process is inherently sterilising, permitting imaging of alanine metabolism \textit{in vivo}. As well as scientific novelty, this overcomes the biggest barrier to clinically translating dDNP.

physics.med-ph↗

Consensus Recommendations for Hyperpolarized [1-13C]pyruvate MRI Multi-center Human Studies

Magnetic resonance imaging of hyperpolarized (HP) [1-13C]pyruvate allows in-vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. Consensus on best practice for multi-center studies is required to develop clinical applications. This paper presents the results of a 2-round formal consensus building exercise carried out by experts with HP [1-13C]pyruvate human study experience. Twenty-nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data-analysis; with the goal of providing recommendations and best practice statements on conduct of multi-center human studies of HP [1-13C]pyruvate MRI. Overall, the group reached consensus on approximately two-thirds of 246 statements in the questionnaire, covering 'HP 13C-Pyruvate Preparation', 'MRI System Setup, Calibration, and Phantoms', 'Acquisition and Reconstruction', and 'Data Analysis and Quantification'. Consensus was present across categories, examples include that: (i) different HP pyruvate preparation methods could be used in human studies, but that the same release criteria have to be followed; (ii) site qualification and quality assurance must be performed with phantoms and that the same field strength must be used, but that the rest of the system setup and calibration methods could be determined by individual sites; (iii) the same pulse sequence and reconstruction methods were preferable, but the exact choice should be governed by the anatomical target; (iv) normalized metabolite area-under-curve (AUC) values and metabolite AUC were the preferred metabolism metrics. The work confirmed areas of consensus for multi-center study conduct and identified where further research is required to ascertain best practice.

physics.med-ph↗

In-vivo real-time 13C-MRSI without polarizer on site: across cities transportable hyperpolarization using UV-induced labile radicals

Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging (HP 13C-MRSI) has the potential to greatly improve diagnostic radiology thanks to its unique capability to detect, noninvasively, a wide range of diseases entailing aberrant metabolism. Nevertheless, it struggles to enter everyday clinical practice as an alternative and/or complement to Positron Emission Tomography (PET). Because of the minute-long hyperpolarization lifetime of the MR HP contrast agents, one of the reasons is, differently from PET, the need and financial burden to have the polarizing machine on site and, as close as possible to the MR scanner. In this work, we show that dDNP samples prepared with UV-induced labile radicals can bridge the technical gap with PET and provide MRI facilities with hours-long relaxing HP contrast agents. As a demonstration, we show the first across cities HP 13C-MRSI experiment in vivo and on a clinical scanner for a perfusion/angiography ([1-13C]HP001) and a metabolic ([U-13C, d7]glucose) contrast agent.

physics.med-ph↗