The NIF Bioimaging Facility provides access to advance in vivo micro-CT, multispectral fluorescence and bioluminescence imaging, high frequency ultrasound and photoacoustic imaging and the NIF Flagship magnetic resonance imaging (MRI) instrument.
These systems can image anaesthetised small animals such as mice and rats non-in-invasively with real time physiological monitoring including respiration, animal temperature and heart rate. Animals can be imaged in real time and cells, protein or bacteria tracked over time, to provide a more biologically relevant understanding of tumour growth, disease progression or mechanisms of drug action.
Applications include the study of infectious diseases, oncology, cardiology, molecular biology, neurobiology, musculoskeletal, vascular, respiratory, inflammation, toxicology, metabolism, embryology, animal development, endocrine disruption, drug development and spectroscopy.
In vivo fluorescence imaging
In vivo fluorescence imaging detects the light emitted by a fluorescently tagged gene, molecule or cell in an animal and provides non-invasive analyses of the strength of the fluorescent signal. The light emitted by a fluorophore can be measured and analysed over time in the same live animal enabling tracking of gene expression, disease or tumour progression or the effects of a new drug.
Fluorescent imaging does require an external light source to excite the fluorophore restricting imaging depth and increasing background signals. However, the technique permits the use of a far wider range of fluorescent probes.
In vivo multispectral imaging and unmixing
More than one fluorescent signal can be imaged in vivo simultaneously. Spectral unmixing techniques can be used to unmix (separate) fluorescent signals within the same tissue as well as remove any autofluorescence. This technique enables reliable quantitation of fluorescent signals and improves sensitivity allowing much smaller or fainter in vivo signals to be detected.
In vivo fluorescence imaging is limited in sensitivity by the presence of autofluorescent signals mostly arising from the skin of the animal or food in the gut. The autofluorescence signals mask the fluorescent signals that are actually being measured. Spectral unmixing techniques can be used to remove autofluorescence, improving sensitivity and enabling reliable quantitation of the fluorescent signal of interest.
In vivo bioluminescence imaging
In vivo bioluminescence imaging is a highly sensitive technique for measuring gene expression or for tracking cells non-invasively in a small animal. Bioluminescence is the production and emission of light by a living organism as a result of a chemical reaction between a substrate, for example luciferin and a luciferase enzyme. Cells or genes can be tagged with luciferase and imaged within an animal. Since light is endogenously emitted in response to stimulation no excitation light source is required so background light levels are extremely low and will not obscure low light signals.
In vivo X-ray micro computed tomography (micro-CT)
This technique uses X-rays to non-destructively image samples in 3D. The technique provides high-resolution information about the internal structure of a sample without the need to section or damage the specimen. An in vivo micro-CT system enables non-invasive imaging of an anaesthetised mice or rat, providing 3D detail of tissue or organs within the animal. A series of projection images are collected at different angular rotations through the sample or animal which map the X-ray absorption at each point. The projection images are subsequently reconstructed to form a 3D model of the specimen.
NIF Flagship magnetic resonance imaging (MRI)
Magnetic resonance imaging (MRI) uses applied magnetic fields to non-invasively (and non-destructively) image samples with non-ionising radiation (unlike X-ray based techniques). MRI can rapidly provide excellent in-vivo soft-tissue image contrast for qualitative analyses, 3D images for quantitative volumetric measurements, and access to parameter maps (for example, MR relaxation, diffusion, flow) related to underlying tissue structure. Rapid imaging techniques can also be used to study dynamic processes, such as the cardiac cycle.
A wide range of MRI experiments are available to study organ function, including blood oxygenation level dependent (BOLD) contrast (commonly used for functional MRI), perfusion, and vascular imaging. In addition, magnetic resonance spectroscopy (MRS) enables in-vivo NMR spectroscopy measurements to be made from predefined volumes of interest, and facilitates the linkage of underlying biochemical processes to disease progression, treatment and the like.
MRI studies on nuclei other than protons (H-1) are also possible, including C-13, F-19, Na-23, and P-31.
High Frequency Ultrasound and Photoacoustic Imaging
Our High Frequency Ultrasound transducers deliver an acoustic pulse into the small animal’s body. Tissues of different densities absorb and reflect sound waves differently resulting in high-resolution grayscale images when the partially reflected sound waves return to the transducer.
Photoacoustic imaging allows the delivery of light energy that is absorbed by tissues causing a thermoelastic expansion. This expansion then generates ultrasound waves that are detected by the transducer and produce images of optical absorption contrast within tissues. New laser technology provides faster, more sensitive image acquisition at a wider wavelength range (680 - 970 nm and 1200 - 2000 nm).