Preclinical studies of inflammation with multimodal in vivo optical imaging

In vivo optical inflammation imaging

Multimodal in vivo optical imaging of inflammation involves several imaging techniques to comprehend the details of health conditions associated with inflammation. It has been employed in various preclinical models and is able to depict inflammation and immunobiology of the subject in studies of infection, orthopedics, autoimmunity and oncology.

The imaging technique allows cells and molecular events involved with the inflammatory process to be monitored. Increased blood flow to the site is linked to inflammation and immune activation, and optical inflammation imaging probes can monitor these changes and detect signs of hyperemia. Preclinical imaging also offers the ability to evaluate candidates and make therapeutic and drug delivery decisions based on the results. X-ray imaging enables anatomical changes associated with inflammatory conditions to be visualized. Probes can detect inflammatory molecules involved in the signaling cascades, even in early stages of the inflammatory response.

Fluorescence optical imaging may offer the advantage of guiding surgical procedures, with its ability to produce near-instant images that depict specific areas affected. There are several techniques used to create fluorescence required for fluorescence imaging. Fluorophores may be endogenous molecules such as hemoglobin or exogenous synthetic optical probes and both can be excited using an external light source or with another agent.

A lipophilic near-infrared (NIR) agent known as Invitrogen (DiR) can be used to label the macrophage cells fluorescently. Macrophage cells labelled by this agent administered via intravenous injection create a short-term method of monitoring the infiltration of the cells. Indocyanine Green (ICG) is an agent characterized by its quick ability to bind to plasma proteins and builds up in inflamed areas of the body, as a result of the increased blood flow to the site.

Lymph drainage using ICG. One nM ICG was administered SQ. Three hours PI in vivo fluorescent imaging was performed using the Bruker In-Vivo Xtreme. Inguinal lymph node and lymph vessels are clearly visible.

Lymph drainage using ICG. One nM ICG was administered SQ. Three hours PI in vivo fluorescent imaging was performed using the Bruker In-Vivo Xtreme. Inguinal lymph node and lymph vessels are clearly visible.
Neutrophil MPO detection in TBI model. Fluorescent apoptosis specific probe PSVue794 (blue) and 5 mg luminol MPO (fire) were administered 1 hr and 4 hr respectively post TBI (cryolesion). Sequential X-ray, luminescence and fluorescence imaging was performed using the In-Vivo Xtreme (control animal at left).
Neutrophil MPO detection in TBI model. Fluorescent apoptosis specific probe PSVue794 (blue) and 5 mg luminol MPO (fire) were administered 1 hr and 4 hr respectively post TBI (cryolesion). Sequential X-ray, luminescence and fluorescence imaging was performed using the In-Vivo Xtreme (control animal at left).

Research using inflammation imaging

It is a widespread practice for white blood cells to be radiolabeled and used to monitor inflammation or infection. Using similar principles, it is possible for NIR Invitrogen to label macrophage cells with fluorescence and model granuloma formulation. This effect has been used in a model of experimental mice and allows the short-term infiltration of macrophage cells to be observed. The bacterial endotoxin lipopolysaccharide (LPS) was used to induce inflammation in the hind flank and the infiltration of the fluorescently labelled macrophage cells injected was monitored for the following seven days.

ICG has been used in several studies with fluorescent in vivo imaging to depict the structure lymphatic system and efficacy of the drainage system. A rat model utilized intravenous administration of ICG to demonstrate early detection of antigen-induced arthritis, which proved to be a sensitive test.

Combined with multimodal X-ray detection, preclinical optical imaging can provide a more comprehensive model of the inflammation associated with arthritis. Collagen induced arthritis (CIA) is associated with inflammation and upregulation of endothelium leukocyte adhesion molecule E-selectin and, as a result, an NIT probe has been developed with specificity this. This has been used in research to evaluate therapeutic response of candidates using a bispecific ligand trap RB200.

Alternative probes have been designed with specificity to inflammatory markers involved with signaling cascades and respiratory burst. These are able to recognize early signs of inflammatory response with a high specificity. In vivo models of contact dermatitis, CIA and Leishmania infection have shown that the probes prove to be useful in the detection of inflammation.

Multimodal in vivo optical imaging systems

Multimodal in vivo optical imaging systems have been used in various preclinical studies in the field of inflammation and immunobiology and are able to detect and monitor inflammatory markers, drug delivery and track immune cells.

The Bruker In-Vivo Multispectral FX PRO and the In-Vivo Xtreme systems can be used to create an effective multimodal optical imaging system. They offer bioluminescence, fluorescence, radioisotopic and X-ray imaging to assist with in vivo research and also allow the selection of flexible probes. These Bruker platforms have been used to create the inflammation and immunobiology research outlined in this article and offer highest industry standard imaging solutions.

References

About Bruker

Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI).

Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI ,EPR and Time-Domain (TD) NMR.

In addition Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research.

Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.


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Last updated: Jun 30, 2015 at 4:24 AM

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