“The Brain Stress Test” David J. Mikulis, MD Dept. of Medical Imaging Division of Neuroradiology
Major Cause of Cerebral Ischemia: Atherosclerosis • Mechanisms: – Fibrin platelet emboli – Blood flow restriction (hemodynamic compromise) • Treatment: – Medical • Anti-platelet agents • Statins – Revascularization: • Endarterectomy • Angioplasty and stent • By-pass surgery
Cerebral Collateral Circulation right left Effectiveness of collaterals: 0 -100%
Hemodynamic Compromise • For a given stenosis, risk of ischemic events increases if there is associated hemodynamic compromise • If hemodynamic compromise is present, then revascularization is indicated
But! • Testing for hemodynamic compromise is not routinely performed • Reasons: – Existing tests such as ultrasound and SPECT suffer from accuracy, reliability and reproducibility issues
Solution: “The Brain Stress Test” • Device (Respir. Act TM) delivers precise, brief, and reproducible CO 2 stimuli • Combine with MRI blood flow imaging • Maps hemodynamic reserve in the whole brain
Brain Stress Test Components CO 2 induced vasodilation is the “stress” stimulus Respir. Act. TM precisely controls arterial CO 2 levels MRI measures changes in brain blood flow Patient placed in MRI while breathing on device
Normal Brain Stress Test Increasing vasodilation Vasodilation exhausted “Steal physiology” Red, orange, and yellow colors = vessels can provide healthy increases in blood flow
Two patients with TIAs right Up to 5 x higher risk for stroke! left right left
Challenges: Developing the test • CO 2 stimulus – Model based end-tidal prospective targeting • Highly accurate and reproducible arterial CO 2 levels – Stimulus selection based on 15 yrs of refinement • • Compatible with MRI environment Data analysis standardized UHN spin-off building the Respir. Act (RA) 4 th generation of the device “plug-and-play”
Advantages Over Other Methods • • • Accurate and reproducible results across sites 15 minute acquisition time High resolution full brain mapping Add-on to existing MRI protocols Safe – Non-invasive – No injection of drugs (ACTZ) – No ionizing radiation
Challenge: Clinical Implementation • Who can do this test? – If you have a 3 T MRI, you can run the test • Will neurologists and surgeons order it? – 1000 studies in 800 patients from UHN, SMH, Sunnybrook, and HSC
Current Challenges 1. Health Canada approval – underway 2. Clinical outcomes – underway (see poster at this meeting showing benefits in a clinical series) 3. Knowledge transfer – how to inform physicians that the test is available and can inform management? 4. How to make the test widely available and a commercial success? 5. Financial sourcing to disseminate? – Cost for devices, disposables, MRI time, and OHIP reimbursement
Thanks to the Innovation Fund for supporting this work Crawley Duffin Holmes Mandell Mcketton Poublanc Russell Sam Sobczyk Lashmi Venkatraghavan Joseph Fisher David Mikulis
Measurement of cerebrovascular reactivity using BOLD-MRI combined with precise controlled changes in carbon dioxide. Is this new brain stress test? Dr L Venkatraghavan*, Dr D Mikulis, # Dr J Fisher, * Dr M Tymianski ** Department of Anesthesia*, Joint Department of Medical imaging#, Division Of Neurosurgery**, University Health Network,
Recent Evidence Suggests Need for Testing Hemodynamic Status • 112 patients with symptomatic carotid stenosis screened for hemodynamic insufficiency using SPECT ACTZ • Cerebral ischemic events over mean follow-up of 34 months – By-pass group = 13% – Medical group = 45% • Absolute risk reduction 32% (p = 0. 008) Low SW et al. J Neurosurg. 2015 Sep; 123(3): 662 -9. doi: 10. 3171/2014. 11. JNS 141553
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