1. “The Brain Stress Test”
David J. Mikulis, MD
Dept. of Medical Imaging
Division of Neuroradiology

2. 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

3. Cerebral Collateral Circulation
right
left
Effectiveness of collaterals: %

4. 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

5. But! Testing for hemodynamic compromise is not routinely performed
Reasons:
Existing tests such as ultrasound and SPECT suffer from accuracy, reliability and reproducibility issues

6. 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

7. Brain Stress Test Components
CO2 induced vasodilation is the “stress” stimulus
MRI measures changes in brain blood flow
RespirActTM precisely
controls arterial CO2 levels
Patient placed in MRI
while breathing on device

8. Normal Brain Stress Test
Vasodilation exhausted
“Steal physiology”
Increasing
vasodilation
Red, orange, and yellow colors = vessels can provide healthy increases in blood flow

9. Two patients with TIAs Up to 5x higher risk for stroke! right left

10. 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”

11. 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
Standardized test!

12. 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

13. Current Challenges Health Canada approval – underway
Clinical outcomes – underway (see poster at this meeting showing benefits in a clinical series)
Knowledge transfer – how to inform physicians that the test is available and can inform management?
How to make the test widely available and a commercial success?
Financial sourcing to disseminate?
Cost for devices, disposables, MRI time, and OHIP reimbursement

14. Thanks to the Innovation Fund for supporting this work
Crawley
Duffin
Holmes
Mandell
Mcketton
Poublanc
Russell
Sam
Sobczyk
Lashmi
Venkatraghavan
Joseph Fisher
David Mikulis

15. Dr L Venkatraghavan*, Dr D Mikulis, # Dr J Fisher,* Dr M Tymianski **
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,
Results
109 patients were recruited
Intracranial stenosis with Moyamoya disease -72, Carotid stenosis – 24, Cerebral vasculitis -8, Others -5
9 Patients excluded due to movement in MRI
100 Patients were included
Mean age -56 yrs, M: F 32:68
Normal CVR 24
Impaired CVR 76
Interventions (59)
CEA/ Stent - 6
EC-IC bypass – 53
(11 bilateral, 7 indirect)
No Intervention
Outcome
1 year:
2 Strokes
Outcome
3 months:
47/59 – Clinical & CVR Improved 1 year:
51/59 – Improved CVR
2 patients had stroke ( contralateral)

16. 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 Sep;123(3): doi: / JNS141553