Edinburgh Preclinical Imaging (EPI)
- About EPI
- Magnetic Resonance Imaging
- Preclinical Ultrasound Imaging Facility
- Optical Imaging
- EPI Research Committee
- Selected recent publications
Edinburgh Preclinical imaging is a state-of-the-art facility providing in vivo, non-invasive imaging of structure and function of all organs and tissues of the body. EPI houses 3 imaging modalities: high-field magnetic resonance imaging (MRI), ultrasound and optical imaging. The facility is within the campus at Little France where it is ideally placed to provide cross-disciplinary work in cardiovascular biology, neuroscience and physiology. We aim to establish an integrated strategy for the development and application of novel in vivo imaging technologies to further understand the mechanisms of disease and develop therapeutic strategies.
• MRI • ULTRASOUND • OPTICAL •
Magnetic Resonance Imaging
Imaging has become a powerful research tool in medicine, enabling the non-invasive detection of biomarkers of disease. Whilst clinical imaging such as CT, MRI and ultrasound is nowadays widespread, the scaling down of these techniques for translational preclinical imaging is less well established.
The University boasts a state-of-the-art preclinical MRI facility that is available for collaborative studies with internal and external researchers. It enables the collection of anatomical, functional and dynamic imaging data from living experimental animals, including genetically modified models. Being embedded within the animal house permits longitudinal in vivo studies generating data that is more powerful than conventional histology alone and satisfies the requirements for reduction and refinement.
The preclinical MRI facility is directed by Professor Ian Marshall, an MR physicist with 20 years’ experience of clinical and preclinical imaging. The facility is managed by Dr Maurits Jansen, a medical biologist with more than ten years’ experience of preclinical imaging and special expertise in cardiac imaging.
Best known for its highly detailed images of soft tissues (such as the brain and liver), MRI is an extremely versatile modality that can also be used to collect dynamic, functional and metabolic information in vivo. Specialised techniques enable the study of fat distribution, brain microstructure and metabolism, brain function and cardiac function. Ex vivo scanning is also possible to achieve the highest possible spatial resolution. The equipment consists of a 7T superconducting scanner that can accommodate mice, rats and rabbits. A range of magnetic field gradients and radiofrequency probes ensures optimum image quality for each application. The system is also fully equipped to measure signals from other NMR sensitive nuclei, in particular Carbon-13, Fluorine-19 and Phosphorus-31. Examples of their use include research into the metabolism of fluorinated drugs, and cellular metabolism using 31P.
Examples of MRI Techniques
Whole body imaging
The 3-dimensional capability of MRI readily allows the complete coverage of an experimental animal, for example to determine the distribution of fat.
Brain structure and microstructure
Standard anatomical imaging provides in-plane resolution of the order of 100μm, whilst diffusion-weighted imaging provides image contrast based on the microstructure of white matter fibres. Quantitative analysis of diffusivity, anisotropy and tract characteristics is proving useful in the investigation of neurodegenerative diseases such as dementia.
(from left to right) T2-weighted fast spin echo image, mean diffusivity, fractional anisotropy and fibre direction maps. 300μm resolution. Stack of 20 slices acquired in 40 minutes (Horsburgh lab).
Small changes in local blood flow and oxygenation accompany neuronal activity and lead to intensity changes on suitable MRI images. By comparing images acquired at ‘baseline’ with those acquired during a specific ‘condition’ (e.g. visual stimulation), maps of brain activity can be generated.
For more information on how we created a study-specific rat brain template for use in SPM analysis of fMRI data, click on the link on the left hand side under 'attachments'.
Dynamic cardiac imaging
(left) short axis and (middle) 4-chamber cine images of a mouse heart. (right) A Gadolinium contrast agent can be used to measure infarct size (pale grey myocardium). Images at twelve different phases of the cardiac cycle are acquired in approximately 3 minutes (Gray lab).
The magnetic properties of the haemoglobin in the blood change with oxygenation and this can be imaged non-invasively by blood oxygenation level-dependent MRI (BOLD MRI); deoxyhaemoglobin acting as an endogenous contrast agent.
Parametric maps of a mouse kidney; on the M0 image, the anatomy of the kidney is clearly visible. When the O2 concentration of the gas mixture the animal was breathing was decreased, the MRI parameter T2* also decreased, indicating poorer oxygenation of the kidney. This technique can be used to investigate the pathofysiology of kidneys of different transgenic mouse models for kidney diseases characterised by hypertension and hypokalaemia (Bailey lab).
Preclinical Ultrasound Imaging Facility
The Vevo 770 high resolution ultrasound scanner imaging system is for in vivo, REAL-TIME, non-invasive small animal research. The scanning facilitates visualisation and measurement of small animal anatomy and the quantification of physiology in adult, neo-natal and (in utero) embryonic small animals. Image resolution of anatomical and physiological structures of 60 microns can be achieved.
Located in Room 13 in Phase 2 of the Biological Research Facility at Little France, the preclinical ultrasound imaging facility is managed by Dr Carmel M Moran while Mr Adrian Thomson performs the high resolution ultrasound scanning.
To book the high resolution ultrasound scanner, click here.
The Vevo 770 scanner gives the cardiovascular researcher the ability to image in vivo the functionality of small animal anatomical and physiological features as well as the ability to measure blood flow. The system provides the ability to perform longitudinal studies of disease progression and regression in individual subjects.
A normal and infarcted long-axis view of a rat heart (Gray lab).
Using Pulsed Wave Doppler function, researchers can evaluate quantitatively the physiological function of the developing mouse organs and associated major vessels, all in real-time. In addition, contrast agents can be infused and measured quantitatively in real-time (using contrast specific imaging) as they enter the kidney vasculature.
The 3D package allows users to view a series of 2D images as a 3D volume and analyze any arbitrary plane and perform 3D volume measurements.
The Vevo 770 allows the researcher to visualize image-guided needle injections and extractions. Targeted injections of cells, genetic material, drugs and retroviruses can be visualized from small animal embryos through to adulthood.
Using our highest resolution, both zebrafish and mice embryos can be visualised.
The preclinical optical imaging facility incorporates three advanced in vivo optical imaging systems providing research opportunities for high-sensitivity imaging of radioisotopic, bioluminescence and fluorescence reporters. This will facilitate non-invasive, longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals (images courtesy of the Optical Imaging Group of the Centre for Inflammation Research).
In vivo Fluorescence Imaging System that performs fluorescence imaging primarily using transillumination to provide quantitative data regardless of depth in mice. Two Imaging modes: Reflectance Imaging and 3D Fluorescence-based Quantitative Tomography. Available laser wavelengths: Excitation = 670 nm, Emission = 700 nm or Channel 2: Excitation = 745 nm, Emission = 780 nm.
Caliper IVIS | Spectrum
• Twenty eight high efficiency filters spanning 430 – 850nm
KODAK Multispectral System FX
EPI Research Committee
The research committee oversees the smooth running of the imaging facilities. It comprises of medical physicists and biomedical scientists who have an interest in using imaging techniques in their research. If you have an interest in using EPI facilities then contact Maurits Jansen (Co-ordinator of EPI) and he will instigate discussion with the appropriate members of the committee to advise on the appropriate imaging modalities and protocols to use.
Prof Megan Holmes (Chair) Interests: Neuroscience, cardiovascular, neuroendocrinology. Modalities: fMRI, MRS, ultrasound
Prof Ian Marshall (Head of MRI facility)
Dr Carmel Moran (Head of Ultrasound facility)
Dr Maurits Jansen (Co-ordinator of EPI, manager of MRI facility)
Dr Paul Fitch (Co-ordinator of Optical imaging)
Dr Scott Semple: Liason from CRIC
Dr Gillian Gray Interests: Cardiovascular. Modalities: ultrasound, MRI
Dr Karen Horsburgh Interests: brain changes in stroke and Alzheimer's disease. Modalities: MRI
Dr Kev Dhaliwal Interests: Models of Inflammatory disease. Modalities: Optical imaging
Dr Guillermina Girardi Interests: Rodent models of pregnancy complications. Modalities: MRI, ultrasound
Selected recent publications
- Brydges NM, Whalley HC, Jansen MA, Merrifield GD, Wood ER, Lawrie SM, Wynne SM, Day M, Fleetwood-Walker S, Steele D, Marshall I, Hall J, Holmes MC. Imaging conditioned fear circuitry using awake rodent FMRI. PLoS One. 2013;8(1):e54197.
- Gray GA, White CI, Thomson A, Marshall I, Kozak AM, Moran CM, Jansen MA. Imaging the healing myocardial infarct-ultrasound, MRI and near-infrared fluorescence. Exp Physiol. 2012 Oct 12. [Epub ahead of print]
- Fortune S, Jansen MA, Anderson T, Gray GA, Schneider JE, Hoskins PR, Marshall I. Development and characterization of rodent cardiac phantoms: comparison with in vivo cardiac imaging. Magn Reson Imaging. 2012 Oct;30(8):1186-91.
- Evans LC, Livingstone DE, Kenyon CJ, Jansen MA, Dear JW, Mullins JJ, Bailey MA. A urine-concentrating defect in 11β-hydroxysteroid dehydrogenase type 2 null mice. Am J Physiol Renal Physiol. 2012 Aug 15;303(4):F494-502.
- Holland P, Bastin M, Jansen MA, Merrifield GD, Coltman RB, Scott F, Nowers H, Khallout K, Marshall I, Wardlaw JM, Deary IJ, McCulloch J, Horsburgh K. MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice (2010). Neurobiology of Ageing, 32(12):2325.e1-6
- Jackson SJ, Hussey R, Jansen MA, Merrifield GD, Marshall I, Maclullich A, Yau JL, Bast T. Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl(2): Hippocampal signal enhancement without disruption of hippocampus-dependent behaviour (2011). Behav Brain Res 216(1), 293-300
- Dhaliwal K, Alexander L, Escher G, Unciti-Broceta A, Jansen M, Mcdonald N, Cardenas-Maestre JM, Sanchez-Martin R, Simpson J, Haslett C, Bradley M. Multi-modal molecular imaging approaches to detect primary cells in preclinical models (2011) Faraday Discuss, 149, 115-123
- Thrippleton MJ, Bastin ME, Munro KI, Williams AR, Oniscu A, Jansen MA, Merrifield GD, McKillop G, Newby DE, Semple SI, Marshall I, Critchley HO. Ex Vivo Diffusion Tensor MRI of the Fibroid Uterus at 7 Tesla: a Novel Method for Assessing Tissue Morphology (2011) J Magn Reson Imaging 34(6):1445-51
- McSweeney SJ, Hadoke PWF, Kozak A, Small GR, Khalid H, Walker BR & Gray GA. Improved cardiac function follows enhanced inflammatory cell recruitment and angiogenesis in 11β-hydroxysteroid dehydrogenase type 1 deficient mice post-MI. (2010) Cardiovasc Res 88, 159-167.
- Smith, LB ; Hadoke, PWF; Dyer E,; Denvir, MA ; Brownstein, D ; Miller, E ; Nelson, N ; Wells, S ; Cheeseman, M ; Greenfield, A Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel model of the vascular type of Ehlers-Danlos syndrome (2011) Cardiovasc Res 90:182-190
- Moran C M, Pye SD, Ellis W, Janeczko A, Morris KD, McNeilly AS, Fraser HM. A Comparison of the Imaging Performance of High Resolution Ultrasound Scanners for Pre-clinical Imaging (2011) Ultrasound Med Biol 37;493-501
- Sun C, Pye S, Janeczko A, Ellis B, Brewin M, Butler M, Sboros V, Thomson A, Browne J, Moran C. The acoustic attenuation of an IEC agar-based tissue-mimicking material measured at 12 - 47 MHz (2011). IEEE proceedings (In press)
- Dhaliwal K, Escher G, Unciti-Broceta A, McDonald N, Simpson JA, Haslett C and Bradley M. Far red and NIR dye-peptoid conjugates for efficient immune cell labelling and tracking in preclinical models (2011). Med Chem Commun, 2, 1050-1053
- Unciti-Broceta A, Moggio L, Dhaliwal K, Pidgeon L, Finlayson K, Haslett C and Bradley M. Safe and efficient in vitro and in vivo gene delivery: tripodal cationic lipids with programmed biodegradability (2011). J Mater Chem, 21, 2154-2158
- Alexander L, Dhaliwal K, Simpson J, Bradley M. Dunking doughnuts into cells--selective cellular translocation and in vivo analysis of polymeric micro- doughnuts (2008). Chem Commun (Camb), 30, 3507-9
- Sun C, Pye SD, Browne JE, Janeczko A, Ellis B, Butler MB, Sboros V, Thomson AJW, Brewin MP, Earnshaw CLH, Moran CM. The speed of sound and attenuation of an IEC agar-based tissue-imicking material for high frequency ultrasound applications. Ultrasound Medicine and Biology (in press)