arXiv subjects

Christoffer Laustsen

Publications and source records attributed to Christoffer Laustsen.

7 recordsLinked to original sources

arXiv2025

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↗

arXiv2025

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↗

arXiv2025

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↗

arXiv2023

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the HP 13C MRI Consensus Group as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality.

physics.med-ph↗

arXiv2021

Di-chromatic Interpolation of Magnetic Resonance Metabolic Imagery

Magnetic resonance imaging with hyperpolarized contrast agents can provide unprecedented \textit{in-vivo} measurements of metabolism, but yields images that are lower resolution than that achieved with proton anatomical imaging. In order to spatially localize the metabolic activity, the metabolic image must be interpolated to the size of the proton image. The most common methods for choosing the unknown values rely exclusively on values of the original un-interpolated image. In this work, we present an alternative method that uses the higher-resolution proton image to provide additional spatial structure. The interpolated image is the result of a convex optimization algorithm which is solved with the Fast Iterative Shrinkage Threshold Algorithm (FISTA). Results are shown with images of hyperpolarized pyruvate, lactate, and bicarbonate using data of the heart and brain from healthy human volunteers, a healthy porcine heart, and a human with prostate cancer.

eess.IV↗

arXiv2019

The detection of acute kidney injury with hyperpolarized 13C Urea and multi-exponential fitting

Purpose: To assess the utility of Laplacian fitting to describe the differences in hyperpolarized 13C urea T2 relaxation in ischemic and healthy rodent kidneys. Theory and Methods: Six rats with unilateral renal ischemia were investigated. 13C urea T2 mapping was undertaken with a radial fast spin echo method, with subsequent post-processing performed with regularised Laplacian fitting. Results: Simulations showed that Laplacian fitting was stable down to a signal to noise ratio of 20. In vivo results showed a significant increase in the mono- and decrease in bi-exponential pools in IRI kidneys, in comparison to healthy (14+-10% vs 4+-2%, 85+-10% vs 95+-3%, p<0.05). Conclusion: We demonstrate, for the first time, the differences in multi-exponential behaviour of 13C,15N2-urea between the healthy and ischemic rodent kidney. The distribution of relaxation pools were found to be both visually and numerically significantly different. The ability to improve the information level in hyperpolarized MR, by utilizing the relaxation contrast mechanisms is an appealing option, that can easily be adopted in large animals and even in clinical studies in the near future.

physics.med-ph↗

arXiv2014

Superparamagnetic iron oxide polyacrylic acid coated γ-Fe2O3 nanoparticles does not affect kidney function but causes acute effect on the cardiovascular function in healthy mice

This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe2O3 NPs (10 mg kg-1) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid-base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 and 7.41 in mice 0.5 h after injections of saline or NP, and did not change over the next 12h. In addition, the injections of NP did not affect arterial PCO2 or [HCO3-] either. Twenty-four and 96h after NP injections, the GFR averaged 11.0 and 13.0 ml min-1 g-1, respectively, values which were statistically comparable with controls (14.0 and 14.0 ml min-1 g-1). Mean arterial blood pressure (MAP) decreased 12-24h after NP injections (111 vs 123 min-1) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterise endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure.

physics.med-ph↗