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27 Nov 17. Job - PhD vacancy (DTP6)

Project title: Multimodal MRI methods to quantify blood-brain barrier dysfunction in the ageing brain (iCase).

Doctoral Training Programme (DTP) in Precision Medicine
Deadline: 5pm on Wednesday 10th January 2018.
Full details here.
Apply here.  
Supervisors:
  • Dr MJ Thrippleton
  • Prof JM Wardlaw
  • Prof I Marshall
Location:
Background

Cognitive impairment and dementia affect over 45 million people worldwide and cost over £26 billion per year in the UK alone.  Currently, there are no disease modifying treatments, and the number of people with the disease is rapidly increasing as our population ages.  A clearer understanding of the pathophysiology is needed to guide the development of effective therapeutics. Vascular dysfunction including blood-brain barrier dysfunction, is an important but poorly understood component of ageing that appears to be accelerated in Vascular, Alzheimer’s and mixed dementias.[1] It includes impaired vasoreactivity (CVR) and interstitial fluid (ISF) drainage. The relative contribution of each to brain injury and symptom development and the sequence of pathology is unknown.

Aims

The project will develop methods to improve detection of subtle BBB leakage through traditional use of intravenous contrast agents (DCE)[2] in parallel with novel approaches such as arterial spin labeling, which can also provide information on regional cerebral blood flow (CBF).  The project will address limitations of DCE methods to detect BBB dysfunction in cerebral small vessel disease ageing stroke and dementia, identified by an international expert working group funded by the MRC JPND and led by Thrippleton. Specifically, the project will address crucial aspects of the acquisition, such as optimal contrast injection rate, the importance of measuring and correcting for RF field inhomogeneity and pre-contrast T1, temporal resolution and the influence of instrumental artifact, some of which were identified in previous work by Thrippleton.[3] Assumptions behind signal processing strategies will be addressed, including the influence of water exchange and the use of population-averaged blood concentration functions versus individual patient measurements. Finally, the project will address the lack of validation by developing alternative methods of assessing permeability, such as relaxation- or diffusion-weighted arterial spin labeling.

Deadline: 5pm on Wednesday 10th January 2018.
Full details here.
Apply here.