GOLD imaging in acute stroke: further technology development incorporating a perfluorocarbon oxygen carrier (Oxycyte) (360G-Wellcome-102567_Z_13_Z)

Acute ischaemic stroke is common and disabling, but lacks acute treatment options. The thrombolytic drug rt-PA (alteplase), given within 4.5h of onset based on clinical symptoms and basic brain imaging, significantly increases independent recovery, but is under-utilised (<5% of UK patients). Advanced brain imaging offers a means of targeting treatment to a wider population but existing technologies are not widely used because of additional time incurred, and limited diagnostic validation. GOLD (Glasgow-Oxygen-Level-Dependent) is a new combined diagnostic+therapeutic approach in which an IV oxygen carrier perfluorocrabon (Oxycyte) enhances imaging of brain metabolic responses to inhaled oxygen with MRI, differentiating potentially salvageable penumbral tissue from irreversibly damaged tissue. Unlike alternatives, additional imaging time carries no penalty ( time lost is brain lost ) since PFC+oxygen maintains brain viability and reduces ischaemic damage. Goals: 1) Optimise dose for diagnostic sensitivity; 2) Confirm Oxycyte+50%O2 preclinical safety when co-administered with thrombolytics and radiological contrast agents. 3) Establish safety & tolerability in acute ischaemic stroke patients in an ascending dose, randomised, controlled study; 4) Confirm diagnostic imaging feasibility in stroke patients. GOLD will allow individual treatment decisions based on brain pathophysiology, not time alone, widening eligibility and improving safety of rtPA, and stratifying patients for future research.