Seeing is believing: An update on modalities to image inflammation in vivo

Abstract

Inflammation is the body’s adaptive response to noxious and potentially harmful stimuli and conditions such as infection or tissue damage (1–3). What was defined by Celsius as ‘rubor, calor, dolor, and tumor’ has now developed into a challenge for researchers in many fields including systems biology, signal transduction, and physiology. Translation of findings from basic science to clinical applications requires understanding of the underlying processes, development, evaluation, and optimisation of lead compounds as well as diagnosis and staging of patients. All of these stages require a broad spectrum of intravital imaging modalities that cover optical and non-optical, invasive and non-invasive, high resolution and deep tissue penetration techniques. In this theme issue of Thrombosis and Haemostasis we have collected five review articles and two original contributions of experts in the field of intravital imaging of inflammation covering imaging of the various aspects of the inflammatory response including acute inflammatory processes with platelet activation, permeability increases, and leukocyte recruitment as well as processes of rather chronic inflammatory diseases such as angiogenesis. In addition, each contribution also describes usage of different imaging modalities covering a broad spectrum from subcellular imaging to detection at tissue levels as well as clinical applications. This variety of herein described imaging techniques may challenge the reader to cross-bridge and adapt the illustrated methodology for application in different fields of research, or ultimately, stimulate the use of complementary imaging modalities and labelling agents for multimodal imaging. Platelet activation is among the earliest events during the inflammatory processes. Upon vascular injury the haemostatic process must rapidly stanch blood loss while avoiding obstruction of flowing blood within the vessel. In recent years, methods for studying coagulation in vivo such as the ferric chloride injury model and the laser injury model have been standardised. Bellido-Martin et al. highlight imaging modalities that have been employed over the last decade to increase our understanding of fibrin formation and platelet activation (4). Activation of platelets also induces subsequent activation of neutrophils which are of primary importance in regulation of inflammatory transendothelial permeability changes (5). Increases in vascular permeability contribute to containing and resolving the inflammatory cascade as that way complement factors and immunoglobulins may enter the tissue. On the other hand, overzealous oedema formation in e.g. brain injury or acute lung injury may result in fatal outcomes. Kenne and Lindbom review modalities for intravital imaging of inflammatory permeability changes by use of optical (e.g. fluorescence microscopy) as well as of non-optical imaging (e.g. PET and MRI) techniques (6). While the former are primarily employed in experimental setups, the latter are frequently used in clinical settings. The endothelial glycocalyx is one determinant of the endothelial barrier in the microvasculature. Its degradation is known to facilitate leukocyte adhesion and to increase vascular permeability to fluids and proteins. By use of intravital microscopy of the cremaster muscle, Constantinescu et al. show that hyperlipidaemia, a Correspondence to: Remco Megens or Oliver Soehnlein Institute for Cardiovascular Prevention Ludwig-Maximilians-University Munich Pettenkoferstr. 9, 80336 Munich, Germany Tel.: +49 89 5160 4673, Fax: +49 89 5160 4352 E-mail: remco.megens@med.uni-muenchen.de or oliver.soehnlein@med.uni-muenchen.de