Fluorine (19F) MRS and MRI in biomedicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Ruiz-Cabello J
PROVIDER: S-EPMC3051284 | biostudies-other | 2011 Feb
REPOSITORIES: biostudies-other
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Project description:Using fluorinated probes for 19F MRI imaging is an emerging field with potential utility in cellular imaging and cell tracking in vivo, which complements conventional 1H MRI. An attractive feature of 19F-based imaging is that this is a bio-orthogonal nucleus and the naturally abundant isotope is NMR active. A significant hurdle however in the 19F MRI arises from the tendency of organic macromolecules, with multiple fluorocarbon substitutions, to aggregate in the aqueous phase. This aggregation results in significant loss of sensitivity, because the T2 relaxation times of these aggregated 19F species tend to be significantly lower. In this report, we have developed a strategy to covalently trap nanoscopic states with an optimal degree of 19F substitutions, followed by significant enhancement in T2 relaxation times through increased segmental mobility of the side chain substituents facilitated by the stimulus-responsive elements in the polymeric nanogel. In addition to NMR relaxation time based evaluations, the ability to obtain such signals are also evaluated in mouse models. The propensity of these nanoscale assemblies to encapsulate hydrophobic drug molecules and the availability of surfaces for convenient introduction of fluorescent labels suggest the potential of these nanoscale architectures for use in multimodal imaging and therapeutic applications.
| S-EPMC6449047 | biostudies-literature
Project description:UnlabelledBackgroundNon-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present.MethodsCollagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28.ResultsQuantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease.ConclusionThese results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.
| S-EPMC3506445 | biostudies-literature
Project description:PurposeTo a) achieve cardiac 19F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantification.MethodsTheoretical simulations and experimental comparisons of spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at free precession (SSFP) pulse sequences, and phantom validations, were conducted using 19F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell labeling was confirmed using flow cytometry and confocal microscopy. For CPC and macrophage concentration quantification, in vitro and post-mortem cardiac validations were pursued with the use of the transfection agent FuGENE. Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in vivo, and in post-mortem murine skeletal and cardiac applications.ResultsSPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. 19F MRI indicated lack of additional benefits upon label concentrations above 7.5-10 mg/ml/million cells. The minimum detectable CPC load was ~500k (~10k/voxel) in two-dimensional (2D) acquisitions (3-5 min) using the butterfly coil. Additionally, absolute 19F based concentration and intensity estimates (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post-CPC injections in the post-mortem state) scaled linearly with fluorine concentrations. Fast, quantitative cardiac 19F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3-5 min, using a butterfly coil.ConclusionThe developed methodologies achieved in vivo cardiac 19F of exogenously injected labeled CPCs for the first time, accelerating imaging to a total acquisition of a few minutes, providing evidence for their potential for possible translational work.
| S-EPMC5764257 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pone.0190558.].
| S-EPMC6872145 | biostudies-literature
Project description:Fluorine-19 (19F) Magnetic Resonance Imaging (MRI) is an emerging modality for molecular imaging and cell tracking. The hydrophobicity of current exogenous probes, perfluorocarbons (PFCs) and perfluoropolyethers (PFPEs), limits the formulation options available for in vivo applications. Hydrophilic probes permit more formulation flexibility. Further, the broad Nuclear Magnetic Resonance (NMR) chemical shift range of organofluorine species enables multiple probes with unique 19F MR signatures for simultaneous interrogation of distinct molecular targets in vivo. We report herein a flexible approach to stable liposomal formulations of hydrophilic fluorinated molecules (each bearing numerous magnetically equivalent 19F atoms), with 19F encapsulation of up to 22.7?mg/mL and a per particle load of 3.6?×?106 19F atoms. Using a combination of such probes, we demonstrate, with no chemical shift artifacts, the simultaneous imaging of multiple targets within a given target volume by spectral 19F MRI.
| S-EPMC5811496 | biostudies-literature
Project description:Magnetic resonance imaging (MRI) is an important key for non-invasive visualization of immigrating cells in in vivo studies. We use Perflourcarbons (PFC) coupled to green fluorescent protein (GFP) for a 1H and 19F MRI detection. To this end, we engineered synthetic cell surface receptors, “Cargo Internalization Receptors” (CIR), which contain a GFP-nanobody and specifically bind GFP, followed by a rapid internalization of the GFP-PFC particles, but without inducing any signaling in the targeted cells. In order to explore the suitability of different uptake mechanisms we constructed three different CIRs, which contain different cytoplasmic domains that have different internalizations motifs and properties to enable the specific uptake of the GFP-PFC cargo in CIR-transfected cells. We show that the CIR approach is working in vitro, and has the potential to specifically track CIR containing cells by 1H and 19F MRI.
2019-05-27 | GSE106215 | GEO
Project description:Emulsified perfluorocarbons (PFCs) are preferentially phagocytized by monocytes/macrophages and are readily detected by (19)F MRI. This study tests the hypothesis that (19)F MRI can be used to quantitate pulmonary inflammation by tracking of infiltrating PFC-loaded monocytes.Pneumonia was induced in mice by intratracheal instillation of lipopolysaccharides (LPS) followed by intravenous injection of PFCs. Whereas regular (1)H MRI provided no evidence of lung injury 24 hours after LPS, the concurrent (19)F images clearly show PFC accumulation in both pulmonary lobes. Imaging at 48 hours after LPS revealed signals in (1)H images at the same location as the 24-hour (19)F signals. Thus, progressive pneumonia was first predicted by (19)F MRI early after PFC administration. Without LPS, at no time were (19)F signals observed within the lung. Histology and fluorescence-activated cell sorting (FACS) combined with (19)F MRI confirmed the presence of infiltrating PFC-loaded monocytes/macrophages after LPS challenge. Additional experiments with graded doses of LPS demonstrated that (19)F signal intensity strongly correlated with both LPS dose and pathological markers of lung inflammation. In separate studies, dexamethasone and CGS21680 (adenosine 2A receptor agonist) were used to demonstrate the ability of (19)F MRI to monitor anti-inflammatory therapies.PFCs serve as a contrast agent for the prognostic and quantitative assessment of pulmonary inflammation by in vivo (19)F MRI, which is characterized by a high degree of specificity due to the lack of any (19)F background. Because PFCs are biochemically inert, this approach may also be suitable for human applications.
| S-EPMC3138443 | biostudies-literature
Project description:We report a protein-observe (19)F NMR-based ligand titration binding study of human PDI b'x with ?-somatostatin that also emphasises the need to optimise recombinant protein fluorination when using 5- or 6-fluoroindole. This study highlights a recombinant preference for 5-fluoroindole over 6-fluoroindole; most likely due to the influence of fluorine atomic packing within the folded protein structure. Fluorination affords a single (19)F resonance probe to follow displacement of the protein x-linker as ligand is titrated and provides a dissociation constant of 23 ± 4 ?M.
| S-EPMC4157668 | biostudies-literature
Project description:Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor.
| S-EPMC1164700 | biostudies-other
Project description:BackgroundIn this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F-MRI offers unambiguous detection and in vivo quantification of labeled cells.MethodsWe investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. 19F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using 19F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.ResultsImmediately following transplantation, 19F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable 19F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the 19F signal was related to the presence of bystander labeled macrophages, and not original MSC.ConclusionsOur results show that 19F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.
| S-EPMC4358825 | biostudies-literature