Pre-clinical imaging

In vivo imaging offers a range of state-of-the-art pre-clinical imaging modalities and research time on a clinical 3T whole-body MRI scanner. A high-resolution NMR spectrometer is managed as part of this facility. Access is limited to authorised users with safety training in radiation and high magnetic fields.

Pre-clinical imaging is a collaborative Facility that manages a wide range of imaging instrumentation for the CI.

IVIS 200 and an IVIS lumina imaging systems (Perkin Elmer) are available for whole-animal in vivo photonic imaging. These can perform sensitive and relatively high-throughput in vivo bioluminescence imaging (BLI), in conjunction with luciferase labelled cells or tissues. Typical scans take less than one minute and up to five subjects can be imaged at a time. Fluorescence imaging (at defined wavelengths between 400 and 900 nm) can also be performed in vivo, although this approach is less sensitive. A MultiSpectral Optoacoustic Tomography (MSOT) system (iThera Medical) has been acquired recently to enable access to the high contrast of optical imaging with the spatial resolution and penetration depth of ultrasound. Imaging is possible between 680 and 950 nm, at a repetition rate of 10 wavelengths per second, enabling dynamic monitoring of oxygenation and contrast agent uptake. The facility also has several ultrasound systems.

The two Agilent MRI systems have integrated animal monitoring, cardiac and respiratory gating, heating and isoflurane anaesthesia. The 9.4 T has higher sensitivity, whereas the 7 T’s smaller susceptibility effects make it more suitable for techniques such as echo-planar imaging; both perform 1H MRI and multi-nuclear MRS. Improved 1H MRS methods that minimise chemical shift artefacts have been implemented. The core is developing quantitative MT-MRI and motion-insensitive DW-MRI methods for tumours in the abdomen, which are subject to respiratory and cardiac motion.

The core is also developing hyperpolarized 13C MR imaging as a novel cancer imaging tool. This allows the spatial distribution of injected 13C-labelled metabolites to be imaged as well as the metabolites formed from them and this has been used to image tumour response to chemotherapy, tumour pH and necrosis. There are two pre-clinical polarizers in the facility and a clinical device in the Department of Radiology, which is allowing us to translate the core’s preclinical work to the clinic.

The facility houses a NanoScan PET/CT (Mediso, Hungary) and a NanoSPECT (Bioscan, USA) for multimodality radionuclide imaging. These systems offer the greatest sensitivity of any in vivo imaging modality and can provide non-invasive assessment of pharmacological (target tissue exposure, target engagement and functional activity) and biological processes (blood flow, perfusion and metabolism). These scanners have nanomolar sensitivity and good resolution (~0.4 mm for SPECT and ~1 mm for PET) and so are ideal for small animal imaging.

Radiochemistry facilities have been set up in collaboration with the Wolfson Brain Imaging Centre at the University of Cambridge and the Radiopharmacy at Addenbrooke’s Hospital. These facilities include all the techniques necessary for radiolabelling with 99mTc , 111In, 123I for SPECT and 11C, 18F and 64Cu for PET/CT.  Molecular probes currently under investigation include [11C]acetate, [18F]FLT, [18F]FMISO, [18F]FET and [99mTc]C2Am for imaging fatty acid synthesis, proliferation, hypoxia, amino acid uptake and cell death respectively.

We are planning a central imaging database that will allow easy retrieval of images that have been acquired from a single animal using any of the different imaging modalities.