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Early assessment of pulmonary inflammation by 19F MRI in vivo.

ABSTRACT: 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.

SUBMITTER: Ebner B

PROVIDER: S-EPMC3138443 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Early assessment of pulmonary inflammation by 19F MRI in vivo.

Ebner Bernd B Behm Patrick P Jacoby Christoph C Burghoff Sandra S French Brent A BA Schrader Jürgen J Flögel Ulrich U

Circulation. Cardiovascular imaging 20100108 2

<h4>Background</h4>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.<h4>Methods and results</h4>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 ...[more]

PMID: 20061515

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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.

Project description:BackgroundThe brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy.MethodsWe acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature.ResultsThis in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology.ConclusionsThe use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders.Relevance statementIn vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation.Key points• The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T). • In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures. • Ex vivo imaging and histology confirmed all the structures identified in vivo. • χ and frequency imaging revealed more brainstem structures than magnitude imaging.

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Early assessment of pulmonary inflammation by 19F MRI in vivo.

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Early assessment of pulmonary inflammation by 19F MRI in vivo.

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