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MRC Precision Medicine DTP: Novel methods for analysis of total-body Positron Emission Tomography (PET) imaging datasets


Project Description

Background
Non-invasive Positron Emission Tomography (PET) imaging provides in vivo quantification of multidimensional and multiparameter data. PET is able to measure specific biochemical processes in the living body, via assessment of kinetic properties of tissues, owing to the so called “radiotracer principle" [1]. It has served as a valuable biomarker for understanding the development and progression of a variety of diseases; as well as a companion biomarker in drug discovery programmes. Pharmaceutical companies have an avid interest in companion PET biomarkers to support their drug discovery efforts and regulatory bodies often require PET data to confirm target engagement and dosing schedules of new drugs [2].

Currently a new clinical total-body PET scanner [3,4] is in an advanced stage of development. This major advance in instrumentation will allow, for the first time, the scientific community to gain access to continuous all-levels whole-body PET human dynamic datasets – something only currently available for small animals. This new feature will be invaluable for integrated systems level analyses. Introducing the use of whole-body PET to understand and interpret biology at a whole organism level will also allow for quantification of off-target drug engagement. The immediate consequence of this new stream of PET research would include ability to advise pharmaceutical companies better not only on optimal dosage for target engagement (current reality), but instead optimal dosage for target engagement with minimal off-target effects (future reality). There are, however, challenges to fully realizing this potential, in particular harnessing even larger PET datasets and understanding the dynamics of multi-organ systems.

At the University of Edinburgh, Dr Tavares is leading a program of radiotracer discovery and development for various targets, including inflammation (18kD translocator protein, TSPO, radiotracers), angiogenesis (nicotinic alpha7 receptors) and fibrosis (proline analogues). The imaging datasets generated from these research avenues will be made available for data mining and the development of novel image analysis methods proposed in this project. This PhD studentship aims to develop new PET kinetic modelling tools (software and plug ins) to quantify target and off target kinetics of PET radiotracers in the whole-body. Currently available and traditional PET kinetic modelling tools were designed for exclusive modelling of brain PET data. Ultimately, the methods developed here would be useful to pharmaceutical companies and regulators when assessing performance of new medicines. Furthermore, this studentship aims to assess the use of network analysis for mining and interpretation of big PET whole-body datasets (led by Prof Tom Freeman). If successful, this alternative approach would help mining big PET datasets with potential for drug companies and regulators to undertake re-purposing screening exercises more efficiently and rapidly.

Aims
This PhD project is truly a multidisciplinary proposal that brings together cutting-edge specialised molecular imaging expertise from biology, medical physics and bioengineering disciplines. This project aims to develop software and methods of image analysis, which will help extract data from rich multiparameter and multidimensional PET images.

Training outcomes
The student will be primarily based at the Edinburgh Preclinical Imaging (Dr Tavares) facility, a state-of-the-art infrastructure with a unique set up for in vivo preclinical imaging. Adjacent to this facility is the image analysis lab, part of the Edinburgh Imaging-QMRI, where cutting-edge
imaging software is available and novel software is continuously been developed. At the Roslin Institute, cutting-edge network analysis software is currently being developed (Prof Freeman) and its applicability of such software to PET imaging datasets will be explored in this project.
The student will have the opportunity to gain specialized skills in the following techniques: animal biology, medical physics, computer programming, image processing and network analysis, bioengineering, kinetic modelling and in vivo small animal imaging techniques.
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This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location:

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you should contact the primary supervisor prior to making your application. Additional information on the application process if available from the link above.

For more information about Precision Medicine visit:

http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2019

Qualifications criteria: Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualifications, in an appropriate science/technology area.

Residence criteria: The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £14,777 (RCUK rate 2018/19) for UK and EU nationals that meet all required eligibility criteria.

Full eligibility details are available: View Website

Enquiries regarding programme:

References

[1]. Ruth, T., Reports on Progress in Physics, 2009. 72 1-23.
[2]. Brooks, D., NeuroRx, 2005. 2 226–236.
[3]. Xuezhu, Z., et al., Physics in Medicine & Biology, 2017. 62 (6): p. 2465. [4]. Cherry, S.R., et al., Journal of Nuclear Medicine, 2018. 59 (1): p. 3-12.

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