Small animal imaging
Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging modalities that are non-invasive and in vivo have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Techniques such as high-frequency micro-ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) are usually used for anatomical imaging, while optical imaging (fluorescence and bioluminescence), positron emission tomography (PET), and single photon emission computed tomography (SPECT) are usually used for molecular visualizations.
These days, many manufacturers provide multi-modal systems combining the advantages of anatomical modalities such as CT and MR with the functional imaging of PET and SPECT. As in the clinical market, common combinations are SPECT/CT, PET/CT and PET/MR.
Principle: High-frequency micro-ultrasound works through the generation of harmless sound waves from transducers into living systems. As the sound waves propagate through tissue, they are reflected back and picked up by the transducer, and can then be translated into 2D and 3D images. Micro-ultrasound is specifically developed for small animal research, with frequencies ranging from 15 MHz to 80 MHz.
Strengths: Micro-ultrasound is the only real-time imaging modality per se, capturing data at up to 1000 frames per second. This means that not only is it more than capable of visualizing blood flow in vivo, it can even be used to study high speed events such as blood flow and cardiac function in mice. Micro-ultrasound systems are portable, do not require any dedicated facilities, and is extremely cost-effective compared to other systems. It also does not run the risk of confounding results through side-effects of radiation. Currently, imaging of up to 30 µm is possible, allowing the visualization of tiny vasculature in cancer angiogenesis. To image capillaries, this resolution can be further increased to 3-5 µm with the injection of microbubble contrast agents. Furthermore, microbubbles can be conjugated to markers such as activated glycoprotein IIb/IIIa (GPIIb/IIIa) receptors on platelets and clots, αvβ3 integrin, as well as vascular endothelial growth factor receptors (VEGFR), in order to provide molecular visualization. Thus, it is capable of a wide range of applications that can only be achieved through dual imaging modalities such as micro-MRI/PET. Micro-ultrasound devices have unique properties pertaining to an ultrasound research interface, where users of these devices get access to raw data typically unavailable on most commercial ultrasound (micro and non-micro) systems.
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