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27 Feb 17. Job - PhD vacancy

PhD opportunity to stratify lung fibrotic disease using computer-aided CT imaging & integration with molecular endotyping.

PhD opportunity with co-supervision between Edinburgh Imaging and the Precision Medicine Doctoral Training Programme, physically based at the Centre for Inflammation Research, Queen’s Medical Research Institute (QMRI, Edinburgh.

Project Details - Computer-aided CT imaging and integration with molecular endotyping to stratify lung fibrotic disease.

Prof Edwin Van Beek is the Edinburgh Imaging co-supervisor with Dr Nik Hirani, Prof Aziz Sheikh, & Dr Kev Dhallwal.

​Full details - http://www.ed.ac.uk/usher/precision-medicine/how-to-apply/computer-aided-ct-imaging-and-integration  

The project would be particularly suited to candidates with degrees in computational engineering, digital imaging processing, physics, machine learning or allied disciplines. 

The deadline for 17/18 applications will be 5pm on Thursday 23rd March 2017

All applications should be made via the University of Edinburgh: http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

 

Background

Lung fibrotic conditions are a significant burden of disease worldwide and are a cause of approximately 7000 deaths/year in the UK, most of which are due to idiopathic pulmonary fibrosis (IPF). The incidence of IPF is comparable to stomach, liver and cervical cancers, and the survival worse than for breast, colon and stage II lung cancer.

The fibrotic lung diseases, including IPF are highly heterogeneous, and their current classification is inadequate because: 1. It is overly reliant on lung biopsy, an invasive procedure with a 2-7% mortality that many patients will not undergo, leading to a diagnosis of  ‘unclassifiable disease’; 2. It does not reliably inform of either prognosis or treatment efficacy.

In contrast to lung biopsy, all patients will have high-resolution CT imaging as part of the diagnostic work-up, but the clinical reporting of CT’s is subjective and not quantitative.

We and others have studied automated CT texture analysis platforms, such as the Adaptive Multiple Features Method (AMFM) and the Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) and shown their potential clinical utility (1,2). Crucially these platforms have not yet been tested in longitudinal ‘real-world’ cohorts in which ground truth (survival, rate of decline in lung function, response to treatment) is known.

The Edinburgh Lung Fibrosis (ELF) Clinic, image-bank and biobank: We have established a unique prospectively populated database designed to capture the natural history of lung fibrosis allied to a gene- and bio-bank. This is the largest incident cohort of unselected lung fibrosis patients globally. The cohort from 01/01/07-31/12/15 consists of >1100 consecutively presenting patients with lung fibrosis. Less than 1% of our cohort has been lost to follow-up.  All patients have volumetric (high resolution) CT scans and >800 patients have serial scans. CT scans are hosted within National Services Scotland (NSS) and this is co-located with the Farr network in the Edinburgh Farr node, enabling a safe haven analytic environment for imaging, clinical and ‘omic data. This platform is being leveraged by Dr Dhaliwal for lung cancer diagnostics (‘LUNG SOLVE’ http://www.hra.nhs.uk/news/research-summaries/lung-solve-version-3/). 

We have ‘banked’ serum and genomic DNA samples from 1070 subjects from our cohort with longitudinal follow up of >12 months (median 4.8 years) and a complete dataset of variables including disease phenotype according to clinical-,CT-,biopsy-category, serial lung function. We are currently interrogating the serum molecular and genetic signatures from patients, beginning with a semi-biased approach according to known IPF-related targets and our own hypothesis-driven concepts (1,2) and extending to a genome-wide (GWAS and whole exome-sequencing) search of candidate genes. We have established international collaborations with groups that have similar but smaller, less mature datasets in which to validate our findings.

Aims

  1. Develop and test an interactive protocol for classification of CT scans using in house (CALIPER) texture analysis platforms.

  2. Interrogate the Edinburgh lung fibrosis cohort of CTs with a texture analysis platform and integrate with molecular endotype data.

  3. Test and validate key findings in separate datasets globally

Training Outcomes

  1. Methodology to iteratively develop and test automatic and interactive image classification 

  2. Integrate large real world ‘omic datasets through standard statistical and machine learning techniques

  3. Develop collaborative interdisciplinary skills

The project would be particularly suited to candidates with degrees in computational engineering, digital imaging processing, physics, machine learning or allied disciplines. 

References

  1. Idiopathic Pulmonary Fibrosis: Adaptive Multiple Features Method Fibrosis Association with Outcomes. Salisbury ML, Lynch DA, van Beek EJ, Kazerooni EA, Guo J, Xia M, Murray S, Anstrom KJ, Yow E, Martinez FJ, Hoffman EA, Flaherty KR; IPFnet Investigators. Am J Respir Crit Care Med. 2016 Oct 21.
  2. Imaging biomarkers in the clinic. van Beek EJ. Biomark Med. 2016 Oct;10(10):1073-1079
  3. Nicol L, Mills R,  Seth S,  MacKinnon A,  McFarlane P, William W,  Stewart G, Howie S,  Dhaliwal D,  Murchison J,  Hirani N. Prognostically predictive biomarkers for IPF; a longitudinal cohort study of treatment naive patients. ABSTRACT; Quarterly J Med 2016 http://qjmed.oxfordjournals.org/content/109/suppl_1/S38.1
  4. O'Dwyer DN, Armstrong ME, Trujillo G, Cooke G, Keane MP, Fallon PG, Simpson AJ, Millar AB, McGrath EE, Whyte MK, Hirani N, Hogaboam CM, Donnelly SC..The Toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med.2013 Dec 15;188 (12):1442-50

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

For more information about Precision Medicine visit: http://www.ed.ac.uk/usher/precision-medicine