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


   College of Medicine and Veterinary Medicine

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  Dr N Hirani  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

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
-Develop and test an interactive protocol for classification of CT scans using in house (CALIPER) texture analysis platforms.
-Interrogate the Edinburgh lung fibrosis cohort of CTs with a texture analysis platform and integrate with molecular endotype data.
-Test and validate key findings in separate datasets globally

Training Outcomes
-Methodology to iteratively develop and test automatic and interactive image classification
-Integrate large real world ‘omic datasets through standard statistical and machine learning techniques
-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.

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 are encouraged to 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 2017
 
Qualifications criteria: Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or soon will 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 £14,296 (RCUK rate 2016/17) for UK and EU nationals that meet all required eligibility criteria.
 
Full eligibility details are available: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/
 
Enquiries regarding programme: [Email Address Removed]

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

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