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Welcome to the fourth Edinburgh Preclinical Imaging newsletter with news and articles on what we have been doing the past few months. 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. 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.
Below are some examples of studies that we have been conducting the past months. We also have a new Guess-The-Image competition. If you would like to discuss a new project, please get in touch. Contact details can be found on our website.
We hope you will enjoy reading this newsletter.
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Preclinical MRI scanner electronics upgrade
This summer, the electronics of the preclinical MRI scanner will be upgraded with a Bruker Biospec console. A big thanks to Prof Peter Kind and Simons Initiative for the Developing Brain for making this possible. Bruker Biospin is the world leading manufacturer of preclinical imaging systems. The new system will allow us to stay up-to-date with the latest developments in the field of preclinical MRI and explore new avenues. It is anticipated that the new scanner will be in operation from September this year. For more information and examples of new imaging possibilities, please contact Maurits Jansen. Click on the picture below for a brochure with examples of applications.
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New collaboration with Royal (Dick) School of Veterinary Studies: Feline cognitive dysfunction
Professor Danielle Gunn-Moore, professor of Feline Medicine, is an internationally recognised expert in her field. One of her research interests focuses on aging of the feline brain and associated cognitive dysfunction. Cognitive dysfunction syndrome (CDS) is defined as the deterioration of cognitive abilities as a result of ageing. It is a recognised disorder in senior cats and dogs, characterised by specific behavioural changes (such as increased vocalisation, loss of litter box training, and alterations in interactions with family members), when no other medical cause can be found. A study suggests that around 28% of cats between 11 and 14 years of age developed at least one behavioural problem related to CDS; moreover, this percentage was found to increase to 50% in cats over 15 years old. Together with Dr Tobias Schwarz (Senior Lecturer in Diagnostic Imaging) and Lorena Sordo (PhD student), we have developed a protocol to scan post mortem cat brains to study structural changes with age and test whether these changes correlate with clinical signs of dementia.
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First high-resolution T1-weighted MR images of a fixed cat brain (top row) acquired with the 7T preclinical MRI scanner and a tractography image showing the white matter tracts.
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Activation of GPR81 in vivo causes a decrease in renal blood flow, shown by Doppler ultrasound
Natalie K Jones
G protein-coupled receptor 81 (GPR81) is highly expressed in adipocytes and activation by the endogenous ligand lactate or by the specific agonist AZ’5538 inhibits lipolysis. The receptor is also found in non-adipose tissue but the function here is not well understood; recent studies show that GPR81 activation increases blood pressure, an effect which is not seen in GPR81 null mice. Adult male C57BL/6JCrl mice were terminally anaesthetised with Inactin (120mg/mL IP) before cannulation of the jugular vein for IV infusion. Animals were placed in the supine position (Figure 1) and pulse-wave Doppler was used to take measurements of blood flow from the right renal artery (Figure 3). Peak velocity, velocity time integral (VTI) and Pourcelot resistive index were all measured at baseline and over a 5 minute infusion period of both vehicle (5% pH matched Mannitol) and GPR81 agonist (AZ’5538, 3mM) at a rate of 0.2mL/10g/Hr. Compared to vehicle control, both VTI and velocity were significantly reduced (Figure 2). This shows that GPR81 is able to influence renal vascular function and haemodynamics although the mechanisms controlling this are yet to be elucidated. The sensitivity of the renal circulation to GPR81 activation may become physiologically significant when lactate concentration rises, as can occur in renal disease.
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Fig 1. Representative long axis B Mode image taken of the right kidney of C57BL/6JCrl mouse
Right kidney highlighted in blue and blood flow measurements taken along the axis highlighted in yellow.
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Fig 2. AZ’5538 causes a decrease in blood flow in the renal artery
Change in velocity was measured each minute over the 5 minute infusion of 3mM AZ’5538 or vehicle infused at 0.2mL/10g/Hr. Data shown as mean±SEM (n=4). Significance determined using 2 way ANOVA (P=0.0002)
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Fig 3. Doppler blood flow in renal artery. Vehicle infused showing maximum velocities
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18F-Fluoro-prolines as imaging biomarkers of fibrosis
Adriana Tavares
Magnetic resonance imaging can quantify established replacement and diffuse fibrosis using late gadolinium enhancement and T1 mapping. However, it cannot assess the activity of fibrosis directly. Non-invasive metabolic imaging of cardiac fibrosis activity will provide major insights into the development of fibrosis during disease as well as serve as a biomarker for development of novel disease-modifying therapies. This project aims to develop 18F-Fluoro-prolines as positron-emitting radiotracers for non-invasive cardiovascular fibrosis activity imaging. If successful, this approach could be applied to a wide range of cardiovascular disorders with major pathophysiological, diagnostic and clinical relevance. Recently, cis and trans 18F-Fluoro-proline tracers were successfully manufactured in Edinburgh and used for PET scanning of rats with a myocardial infarction. The same animals also underwent MRI scanning using the adjacent MRI facility for comparison. Below are some first images from this exciting new research area.
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Late-Gd MRI (left), 18F-Proline PET (middle) and MR-PET fusion image of a rat heart 10 days after LAD occlusion. Increased uptake of 18F-Fluoro-proline can be seen in the infarct as well as in the chest wall where the incision for the LAD-occlusion surgery was made indicating active fibrosis at this stage of infarct healing.
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Image Competition 4
Click on the video below. What is this? If you can guess what it is, and which imaging modality was used, send an email to m.a.jansen@ed.ac.uk with your solution to be entered in a draw for a chance to win a free imaging session of the preclinical imaging modality of your choice (max 1 hour, contrast agents/radio tracers not included), a selection box or an Amazon voucher. Be as specific as possible. Deadline 30 June 2018.
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Newly awarded grants
ISSF3
PET Imaging Studies Of Transplanted GMP Grade Mesenchymal Stromal Cells That Promote The Long-Term Function Of Human Islets In Type 1 Diabetes. £49,159. PI: Shareen Forbes
Synaptome imaging: development of synapse molecular imaging for neurology and psychiatry. £35,000. PI: Seth Grant
British Heart Foundation Project Grant
Novel imaging biomarker for detection of regional cardiovascular inflammation using Positron Emission Tomography (PET). £276,970. PI: Adriana Tavares.
Carnegie Trust Research Incentive Grant
Selecting hit chemical scaffold from library of novel sphingosine-1-phosphate-5 (S1P5) compounds. 2018; 1 year. £9,955 PI: Adriana Tavares.
SPRINT-MND/MS funded PhD studentship
Imaging myelination/remyelination processes with Positron Emission Tomography (PET) and a selective sphingosine-1-phosphate-5 (S1P5) radiotracer. £76,763 PI: Adriana Tavares.
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Other news
- Recently, Carmel Moran, head of the preclinical ultrasound facility, was promoted to personal Chair, for her outstanding internationally-recognised contribution to ultrasound imaging and its application in translational research. Congratulations, Carmel!
- Mark MacAskill got an oral presentation and Wendy McDougald got a poster presentation at the upcoming World Molecular Imaging Congress (WMIC) 2018 in Seattle USA. Well done, both!
- Edinburgh Imaging organises bi-weekly seminars. Click here for more information.
- Every first Monday of the month, there is a PET is Wonderful (PiW) talk. Please contact Adriana (adriana.tavares@ed.ac.uk) to be included in the email distribution list.
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MacAskill MG, Saif J, Condie A, Jansen MA, MacGillivray TJ, Tavares AAS, Fleisinger L, Spencer HL, Besnier M, Martin E, Biglino G, Newby DE, Hadoke PWF, Mountford JC, Emanueli C, Baker AH. Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product. Mol Ther. 2018 Mar 28.
Forsythe RO, Dweck MR, McBride OMB, Vesey AT, Semple SI, Shah ASV, Adamson PD, Wallace WA, Kaczynski J, Ho W, van Beek EJR, Gray CD, Fletcher A, Lucatelli C, Marin A, Burns P, Tambyraja A, Chalmers RTA, Weir G, Mitchard N, Tavares A, Robson JMJ, Newby DE. (18)F-Sodium Fluoride Uptake in Abdominal Aortic Aneurysms: The SoFIA(3) Study. J Am Coll Cardiol. 2018 Feb 6;71(5):513-523.
Rabell-Montiel A, Thomson AJ, Anderson TA, Pye SD, Moran CM. Acoustic Properties of Small Animal Soft Tissue in the Frequency Range 12-32 MHz. Ultrasound Med Biol. 2018 Mar;44(3):702-713.
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Who's who @ Edinburgh Preclinical Imaging
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Prof. Megan Holmes
Director Edinburgh Preclinical Imaging
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Dr Maurits Jansen
Manager Edinburgh Preclinical Imaging
Manager MRI Facility
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Prof. Ian Marshall
Director Preclinical MRI Facility
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Ross Lennen
MRI Research Associate
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Prof Carmel Moran
Director Preclinical Ultrasound Facility
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Adrian Thomson
Ultrasound and Optical Imaging Research Assistant
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Dr Adriana Tavares
Director Preclinical PET/CT Facility
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Carlos Alcaide
PET/CT Technical Assistant
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Agne Stadulyte
PET/CT Technical Assistant
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