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“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
• 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 (RespirAct TM) delivers precise,
brief, and reproducible CO2 stimuli
• Combine with MRI blood flow imaging
• Maps hemodynamic reserve in the whole
brain
Brain Stress Test Components
CO2 induced vasodilation
is the “stress” stimulus
RespirActTM precisely
controls arterial CO2 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 5x higher risk for stroke!
left
right
left
Challenges: Developing the test
• CO2 stimulus
– Model based end-tidal prospective targeting
• Highly accurate and reproducible arterial CO2 levels
– Stimulus selection based on 15 yrs of refinement
•
•
•
•
Compatible with MRI environment
Data analysis standardized
UHN spin-off building the RespirAct (RA)
4th 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 3T 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.JNS141553
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