Published: October 20th, 2013
We demonstrate how to perform macrophage MR imaging using ultrasmall superparamagnetic contrast agent (USPIO) in septic arthritis, allowing an initial and longitudinal in vivo non-invasive evaluation of macrophages infiltration and an assessment of therapy efficacy.
Macrophages are key-cells in the initiation, the development and the regulation of the inflammatory response to bacterial infection. Macrophages are intensively and increasingly recruited in septic joints from the early phases of infection and the infiltration is supposed to regress once efficient removal of the pathogens is obtained. The ability to identify in vivo macrophage activity in an infected joint can therefore provide two main applications: early detection of acute synovitis and monitoring of therapy.
In vivo noninvasive detection of macrophages can be performed with magnetic resonance imaging using iron nanoparticles such as ultrasmall superparamagnetic iron oxide (USPIO). After intravascular or intraarticular administration, USPIO are specifically phagocytized by activated macrophages, and, due to their magnetic properties, induce signal changes in tissues presenting macrophage infiltration. A quantitative evaluation of the infiltrate is feasible, as the area with signal loss (number of dark pixels) observed on gradient echo MR images after particles injection is correlated with the amount of iron within the tissue and therefore reflects the number of USPIO-loaded cells.
We present here a protocol to perform macrophage imaging using USPIO-enhanced MR imaging in an animal model of septic arthritis, allowing an initial and longitudinal in vivo noninvasive evaluation of macrophages infiltration and an assessment of therapy action.
Magnetic resonance imaging (MRI) is considered to be the imaging modality of choice for the demonstration of infectious synovitis due to its high spatial resolution and soft tissue contrast. Signal changes observed on MRI in arthritis low T1 and high T2 signal reflecting the increased presence of extracellular water content, and a marked enhancement after gadolinium based-contrast agent administration, consistent with the histologically findings of increased vascularity owing to vasodilation and angiogenesis1. Nevertheless, MRI is often unable to demonstrate resolution of infection during antibiotic therapy as persistent enhancement can be observed in the j....
All procedures involving animal subjects have been approved by the University Hospital Institutional Animal Care committee.
1. Intraarticular Bacterial Inoculation
On unenhanced images, the synovium of infected knees presents a diffuse swelling of intermediate signal that is non distinguishable from surrounding soft tissue, while femur and patella appear as low signal structures (Figure 1).
On the USPIO-enhanced images, 24 hr after the contrast agent administration, synovial area containing USPIO-loaded macrophages will demonstrate signal loss (Figures 1 and 2).
While nonspecific gadolinium-based contrast agents provide information about the volume and perfusion of the extracellular space, macrophage imaging by USPIO-enhanced MR allows a precise anatomical localization and a qualitative evaluation of macrophage infiltration within infected synovium without the need of tissue sampling9. Due to their high sensitivity, USPIO can demonstrate even subtle cellular infiltrate present in the early phases of infection. Under successful antibiotic therapy, as the pathogens are .......
|Name of Reagent/Material
|Dose: 150 μmol Fe/kg
|Ketamine (500 mg/ml ketamine)
|Dose: 30 mg/kg
|Rompun (20 mg/ml Xylazine)
|Dose: 4 mg/kg
|Dose: 0.1 mg/kg/8 hr
|BD 22 G, 1 inch
|BD 25 G, 5/8 inch
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