tri preclinical imaging facility: equipment and services

Xstrahl Small Animal Radiation Research Platform (SARRP) (image-guided radiotherapy / stereotactic irradiation)

The SARRP enables replication of the clinical process of image-guided radiotherapy (IGRT) / stereotactic irradiation in the preclinical setting. This capability drives the development of novel and individualised radiotherapy regimens for cancer and other conditions, through enhanced knowledge of the biological response to ionizing radiation at in vivo, cellular and molecular levels.

The workflow involves CT imaging, target localisation, treatment planning, then delivery of orthovoltage (220kV) X-ray beams to precise anatomical targets. Targeted irradiation drastically minimises normal tissue and adjacent tissue damage.

Targeted irradiation is achieved through the use of a selection of fixed collimators (1mm circular, 3mm x 3mm, 3mm x 9mm, 5mm circular, 10mm circular, and 10mm x 10mm) or a variable motorised collimator (from 1mm x 1mm, up to 40mm x 80mm) that enables conformal radiation therapy commonly used in clinical practice. The SARRP can deliver static beams, parallel opposed beams, continuous arc therapies, multiple isocenter treatments, and non-planar arcs.

TRI is home to the first preclinical IGRT / stereotactic irradiator in Queensland.

Visualsonics Vevo 2100/LAZR (high-frequency ultrasound and photoacoustic imaging)

The Vevo LAZR is a fully integrated high-frequency ultrasound and photoacoustic imaging system designed for small laboratory animals. Photoacoustics is a cutting-edge imaging modality which detects ultrasound waves generated by molecules of interest due to thermoelastic expansion following absorption of light (the “photoacoustic effect”). The instrument co-registers anatomical information (high-resolution ultrasound images) with functional data (eg oxygen saturation or nanoparticle distribution).

The ultrasound component (Vevo 2100) is fitted with two high-frequency transducers; MS550S and MS250S. Common high-frequency ultrasound applications include measurement of tissue volume, vascularity (power, colour, and pulsed-wave Doppler), perfusion (microbubble contrast agent), cardiac function, and image-guided injection.

The photoacoustic component is fitted with two transducers; LZ250 and LZ400. Applications include detection and quantification of endogenous contrast agents (oxygenated and deoxygenated haemoglobin, melanin), and exogenous contrast agents such nanoparticles (eg carbon, gold) and dyes (eg indocyanine green, and methylene blue).

Our Vevo LAZR was the first one installed in Australia (2015).

Perkin Elmer IVIS Spectrum (optical imaging)

The IVIS Spectrum enables high sensitivity bioluminescence, fluorescence and/or Cerenkov imaging of samples in vivo, ex vivo and in vitro. The instrument has an ultra-cooled CCD camera designed for optimal detection of low intensity light. The IVIS Spectrum allows for spectral scanning from blue to near-infrared (NIR) wavelengths by using 10 narrow band excitation filters (30nm bandwidth) and 18 narrow band emission filters (20nm bandwidth). The spectral unmixing tool enables separation of multiple fluorescent reporters within the same sample. High throughput imaging (5 mice) is possible with the 23cm FOV, and high resolution (20µm) with the 3.9cm FOV. 

Major applications of optical imaging include monitoring of disease progression (eg primary tumour growth and metastatic spread), tracking of adoptively transferred immune cells, and bio-distribution of fluorescently-labelled nanoparticles. 

Lions Australia Bruker Skyscan 1272  (ultra-high resolution µCT)

The Skyscan 1272 is a state-of-the-art ex vivo µCT scanner capable of producing ultra-high resolution images with a voxel size down to 0.35 µm. With a variable X-ray source (20-100kV) and an automatic 6-position filter changer, samples of ranging densities can be successfully imaged. Rapid 3D reconstruction is enabled through use of the Instarecon 3D reconstruction software. The system is also fitted with a 16-position sample changer, allowing for high-throughput and sequential scanning of multiple samples. Common applications include high-resolution imaging of bone (trabecular), teeth, bone defect models, tumours in soft tissue (liver, lungs etc), biomaterials, and inorganic materials eg wood.

The Skyscan 1272 was purchased by the Mater Foundation using funds donated by the Lions Club of Australia. It was installed in 2017.

Molecubes β-Cube and X-Cube (µPET-CT)

The new benchtop Molecubes µPET-CT system co-registers sequentially acquired PET and CT data from anaesthetised small laboratory animals. 

The PET system (β-Cube) provides sub-millimeter spatial resolution, with a maximal Field of View (FOV) of 130mm (axial) x 72mm (transaxial). High-throughput imaging is achievable due to high detector sensitivity (short acquisition times), use of a multi-mouse hotel (simultaneous imaging of 4 mice), and a user-friendly software graphical interface. Our facility is licensed to handle multiple PET radioisotopes including F18, Zr89, Ga68 and Cu64. Common PET-CT applications include glucose uptake, tumour-specific imaging, bio-distribution of newly developed radiotracers, and brain dopamine metabolism.

The CT component (X-Cube), which utilises a variable X-ray source (20-80kV), enables rapid whole animal imaging (mice and rats) through a large FOV of 63mm (transaxial) x 200mm (axial). CT images are typically reconstructed at 50µm voxel size resolution. The novel respiration gating functionality minimises breathing artefacts, providing clear CT images. The X-Cube can be used independently, and common CT applications include longitudinal assessment of osteogenesis, calcification of biomaterials, osteoporosis, patient-derived explants (samples inside plates), and healing in bone defect models.   

Bruker Minispec LF50H (nuclear magnetic resonance)

The Minispec LF50H uses nuclear magnetic resonance (NMR) principles to accurately quantify fat mass, lean tissue mass and free fluid mass in conscious mice. This method is the gold standard for fat and lean tissue measurement in vivo in the pharmaceutic industry, and diabetes and obesity research institutes worldwide. Very commonly used in mechanism studies on metabolic syndrome.

Key features include: non-invasive and no anaesthesia required (mice just sit inside a tube during imaging), rapid acquisition (approx. 1 min per mouse), supports broad mouse weight range (10-60grams), non-destructive (fat, lean tissue and fluid are not “destroyed” during imaging, ideal for longitudinal studies), and the machine is very user friendly.

Faxitron Ultrafocus 100 (2D X-ray)

The Faxitron Ultrafocus 100 is a fully shielded X-ray cabinet system which allows for rapid acquisition (<10sec) of high resolution 2D X-ray images. At 10X geometric magnification, high resolution images can be acquired (focal spot of 8µm, up to 100 lp/mm). The largest FOV size is 10cm x 15cm, enough for whole small animal imaging. Common applications include assessment of bone structure, calcification of bioengineered implants, x-ray angiography of organs using suitable contrast agents, and imaging of metallic implants or other materials in vivo and ex vivo. 

Perkin Elmer 2480 Wizard (gamma counting)

The 2480 Wizard gamma counter is the premier system for counting high-energy gamma emitters, as well as low activity and environmental samples. With an energy range of 15-2000KeV, up to six different nuclides can be measured simultaneously. The instrument has an automated sample changer for high-throughput counting of 1000 samples. 

Gamma counting is commonly used to determine the bio-distribution profile of molecular probes labelled with PET radioisotopes, or other gamma-producing radioisotopes. Harvested organs are placed inside plastic tubes which are then fed into instrument for ex vivo gamma quantification. 

Targeted radionuclide therapy

Targeted radionuclide therapy involves the use of antibodies, peptides or other bioactive molecules conjugated with radioisotopes which emit toxic radiation. This approach has major applications in oncology. Our facility is currently licensed to handle the following radionuclides for preclinical therapeutic studies:

  • Lutetium (Lu)-177: beta particle emitter
  • Actinium (Ac)-225: alpha particle emitter

High Performance Analysis Computers 

Two high-performance analysis computers running Intel Xeon 16-core processors and dedicated graphics cards are bookable online and free to use. The machines have all the relevant software installed and are are available for analysis and processing of large data sets.

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