1. Stewart Wiseman Brain Research Imaging Centre School of Clinical Sciences PhD - 10 week review January 2013

2. Radiographer Interested in research, research methods, statistics Interested in imaging, chronic inflammatory arthritis and autoimmunity About me BRIC scanner (1.5T GE Signa HDx) 1992-1996 2007-2011 2012-2015

3. Location

4. Overview CSVD Acute lacunar infarct on DWI WMH on FLAIR Cause unknown Role for inflammation? Endothelial dysfunction…* Not large artery atheromatus (but atheroma might be involved, and atherosclerotic disease itself is considered an inflammatory process) * is evident in lacunar stroke versus normal, as measured by vascular response to hypercapnia or infusion of L-arginine. Stevenson et al. 2010. Rheumatic diseases Measureable components Specific diagnoses Inflammatory markers DAS Pain rating Range of joint mobility & muscle weakness - Experts in inflammation Imaging Measureable components White matter hyperintensities Acute lacunar infarcts Lacunes EPVS BMBs - Experts in imaging

5. Related areas (but not our main focus) Inflammatory diseases of the CNS Multiple Sclerosis Neurological complications of rheumatic disease Cord compression Nerve root compression Spontaneous dislocation / subluxation Psychological (eg, in lupus) RA to controls n=11,633 followed over 5 years Incidence of stroke 7 per 1,000 patient years RR 1.4 (95%CI 1.3 to 1.5) Watson et al. J Rheumatol 2003;30:1196–202 Large artery atheromatous and cardio- embolic stroke Associations with rheumatic diseases (eg, higher mortality in RA largely attributed to atherosclerosis; increased plaque burden in lupus)

6. Background reading Learning about and how to do systematic reviews Attended GCP Currently completing a systematic review started in 2009 Started to learn image processing techniques (including use of software tools developed at our Centre) What I have done so far

7. Plasma and serum markers of coagulation, fibrinolysis, endothelial activation and inflammation in lacunar stroke versus other stroke subtypes and non-stroke controls Systematic Review 12 different markers 43 included papers Hopefully Cochrane quality (but not Cochrane registered)

8. Systematic Review Markerfor tPAThrombus / coagulation vWFEndothelial damage ICAMInflammation / endothelial activation VCAMInflammation / endothelial activation PAIThrombus / coagulation E-SelectinInflammation / endothelial activation P-SelectinInflammation / endothelial activation FibrinogenClotting / inflammation CRPInflammation HomocysteineInflammation / endothelial activation D-dimerFibrinolysis IL-6Inflammation

9. Plans for remainder of first year Finish segmenting white matter lesions on Edinburgh Stroke Study Finish systematic review of plasma markers in stroke subtypes Continue reading * Literature review – specific rheumatic diseases and stroke in general Systematic review – TNF-α in ischaemic stroke subtypes Get to grips with data (imaging and inflammatory) held on four studies (Edinburgh Stroke Study, Mild Stroke Study I, Mild Stroke Study II, LBC 1936) Perform analyses thereon Tutoring on our online Masters in neuroimaging Start to plan for a small imaging study on lupus patients * Discussion today would be helpful January Feb - Sept