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Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy. © 2011 Tremoleda et al.

Atherosclerotic lesions have a highly non-uniform distribution in regions of arterial branching and curvature, consistent with hemodynamic factors, in particular wall shear stress (WSS), controlling their development. The widespread and increasing use of the mouse as a model for studying atherosclerosis has encouraged investigation of the hemodynamics of the mouse aortic arch [1–3], in which previous studies have revealed areas of high and low lesion prevalence and variation in the expression of pro-atherogenic molecules [4]. Our previous computational simulations [1–2] did not produce distributions of WSS that explain the pattern of lesions. We are currently investigating whether incorporation of more realistic aortic root velocity measurements, obtained using phase-contrast magnetic resonance imaging (PC-MRI), into these simulations can improve the correlation with disease. Here we present velocities obtained by PC-MRI and preliminary simulations employing the data.

The implementation of imaging technologies has dramatically increased the efficiency of preclinical studies, enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time and testing new therapies. The ability to image live animals is one of the most important advantages of these technologies. However, this also represents an important challenge as, in contrast to human studies, imaging of animals generally requires anaesthesia to restrain the animals and their gross motion. Anaesthetic agents have a profound effect on the physiology of the animal and may thereby confound the image data acquired. It is therefore necessary to select the appropriate anaesthetic regime and to implement suitable systems for monitoring anaesthetised animals during image acquisition. In addition, repeated anaesthesia required for longitudinal studies, the exposure of ionising radiations and the use of contrast agents and/or imaging biomarkers may also have consequences on the physiology of the animal and its response to anaesthesia, which need to be considered while monitoring the animals during imaging studies. We will review the anaesthesia protocols and monitoring systems commonly used during imaging of laboratory rodents. A variety of imaging modalities are used for imaging rodents, including magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computed tomography, high frequency ultrasound and optical imaging techniques such as bioluminescence and fluorescence imaging. While all these modalities are implemented for non-invasive in vivo imaging, there are certain differences in terms of animal handling and preparation, how the monitoring systems are implemented and, importantly, how the imaging procedures themselves can affect mammalian physiology. The most important and critical adverse effects of anaesthetic agents are depression of respiration, cardiovascular system disruption and thermoregulation. When anaesthetising rodents, one must carefully consider if these adverse effects occur at the therapeutic dose required for anaesthesia, if they are likely to affect the image acquisitions and, importantly, if they compromise the well-being of the animals. We will review how these challenges can be successfully addressed through an appropriate understanding of anaesthetic protocols and the implementation of adequate physiological monitoring systems.

Background Acute traumatic coagulopathy (ATC) identified in the first hour of trauma patients is associated with worse outcomes and increased risk of death [1]. Identification of critical coagulation pathways involved in ATC is important for future targeted drug discovery. Previous studies have demonstrated an activation of the thrombomodulin-protein C pathway during ATC [2]. We examined the effect of reduced thrombomodulin generation in an experimental model of ATC.