Molecular imaging of myocardial infarction with Gadofluorine P – A combined magnetic resonance and mass spectrometry imaging approach

Abstract

BackgroundMolecular MRI is becoming increasingly important for preclinical research. Validation of targeted gadolinium probes in tissue however has been cumbersome up to now. Novel methodology to assess gadolinium distribution in tissue after in vivo application is therefore needed.PurposeTo establish combined Magnetic Resonance Imaging (MRI) and Mass Spectrometry Imaging (MSI) for improved detection and quantification of Gadofluorine P deposition in scar formation and myocardial remodeling.Materials and methodsAnimal studies were performed according to institutionally approved protocols. Myocardial infarction was induced by permanent ligation of the left ascending artery (LAD) in C57BL/6J mice. MRI was performed at 7T at 1 week and 6 weeks after myocardial infarction. Gadofluorine P was used for dynamic T1 mapping of extracellular matrix synthesis during myocardial healing and compared to Gd-DTPA. After in vivo imaging contrast agent concentration as well as distribution in tissue were validated and quantified by spatially resolved Matrix-Assisted Laser Desorption Ionization (MALDI) MSI and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) imaging.ResultsBoth Gadofluorine P enhancement as well as local tissue content in the myocardial scar were highest at 15 minutes post injection. R1 values increased from 1 to 6 weeks after MI (1.62 s−1 vs 2.68 s−1, p = 0.059) paralleled by an increase in Gadofluorine P concentration in the infarct from 0.019 mM at 1 week to 0.028 mM at 6 weeks (p = 0.048), whereas Gd-DTPA enhancement showed no differences (3.95 s−1 vs 3.47 s−1, p = 0.701). MALDI-MSI results were corroborated by elemental LA-ICP-MS of Gadolinium in healthy and infarcted myocardium. Histology confirmed increased extracellular matrix synthesis at 6 weeks compared to 1 week.ConclusionAdding quantitative MSI to MR imaging enables a quantitative validation of Gadofluorine P distribution in the heart after MI for molecular imaging.

A novel calibration strategy based on internal standard–spiked gelatine for quantitative bio-imaging by LA-ICP-MS: application to renal localization and quantification of uranium

“…In this work, in-house solid matrix-matched standards were prepared from uranium-spiked kidney homogenate. Nevertheless, further calibration strategies are found in the literature including the solution-based calibration [27], fabrication xerogel solid calibration standards which are more suitable for the calibration of glasses and silicate matrices [28], the synthesis of metal-spiked polymer films [29], the use of dried droplets or dried matrix spots (DMS) deposited on different substrates [30][31][32][33][34], and the spiking and sectioning of gelatine droplets, whose use has increased noticeably in recent years for the quantitative analysis of biological tissues [35][36][37][38][39][40][41]. For internal standardization, three different approaches are mainly described in the literature for the quantitative elemental imaging of biological samples: (i) the simultaneous nebulization of a standard solution [42], (ii) the use of an element naturally occurring in the sample [43][44][45], and (iii) the addition of an internal standard-spiked layer between the sample and support or on the sample [46][47][48][49][50][51].…”

MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice

“…The entire cradle was then centered in the scanner. For enhanced T 1 imaging, gadopentetate dimeglumine (Magnevist) (0.2 mmol/kg) was diluted 1:5 in 0.9% sodium chloride and was injected 5 min before the scan via tail vein catheter (63). The volume of delivered prepared contrast solution was ∼0.2 mL After scanning, mice were given an s.c. saline injection and placed on a heating pad to recover.…”

Mass Spectrometry Imaging of atherosclerosis-affine Gadofluorine following Magnetic Resonance Imaging

“…Generated sections were mounted onto glass slides (VWR, Darmstadt, Germany). For a quantitative analysis, external calibration was performed by using matrix-matched standards based on gelatin prepared as described previously 11 .…”

“…The applicability for Gd-based contrast agents has to be proven since these molecules are highly water-soluble and IMC workflow contains washing and equilibration steps in aqueous solution. Mass spectrometry imaging of gadolinium chelates has been achieved by matrix-assisted laser desorption ionization imaging (MALDI MSI) 9 and laser ablation -inductively coupled plasma -mass spectrometry (LA-ICP-MS) [10][11][12] . Mass spectrometry imaging has been used in the past years to provide comprehensive maps of lipid and protein distribution in experimental and clinical atherosclerosis down to a spatial resolution of 30 μm.…”