Multimodal Imaging of Inflammation at the Neurovascular Interface in Cerebrovascular Disease

A carotid atherosclerotic plaque represents a nidus of inflammation mere centimetres below the blood-brain barrier. This inflammation, along with associated regions of microcalcification, are histopathological features of atheroma at risk of rupture (so-called “vulnerable plaques”) that trigger thromboembolic stroke. While conventional clinical imaging simply measures the degree of vessel stenosis, it is a crude measure that reveals little of the metabolic processes affecting plaque vulnerability. Our research demonstrates the utility of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF), measuring inflammation and microcalcification respectively, to identify culprit carotid atheroma in vivo, and establish how these processes influence plaque vulnerability. Furthermore, for stroke care it is the downstream thromboembolic effects upon the brain that are key. While proinflammatory conditions may increase the risk of stroke, the relationship between atheroma inflammation and the peri-infarct inflammatory response following a stroke remains poorly defined. Our work demonstrates how inflammatory activity in symptomatic carotid atheroma, measured using PET, influences both chronic small vessel disease and the evolution of lesion volume in the post-stroke period. Using metabolic imaging we can both identify vulnerable atheroma in vivo and demonstrate how these processes affect infarct evolution. We show that whilst inflammation is a generalised process, microcalcification is a focal process that may represent a point of maximum vulnerability. These results also reveal the complexity of the atheroma-brain interaction that may simultaneously trigger events while also influencing stroke evolution in the early recovery period. This has important implications for understanding pathophysiology of both atherosclerosis and stroke evolution, advancing drug-discovery, and potential clinical applications to minimise the impact from this devastating disease.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2018

Author dc:creator

• Evans, Nicholas Richard

Advisors dc:contributor.advisor

• Warburton, Elizabeth
• Rudd, James

• Stroke
• Carotid artery
• Atherosclerosis

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d274f47a-a566-42fb-907d-c826ce54e0d1/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

Author Identifier

0000-0002-7640-4701
0000-0003-2243-3117

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/275947