Brain function and physiology using magnetic resonance imaging
Dr. MacIntosh's research involves the study of human brain function and physiology, in health and in disease. The focus of this research has been developing methods to study cerebrovascular disease processes that relate to stroke. In addition to disabling acute stroke there are also short-lived events called transient ischemic attacks. Finally, there are also silent strokes, which are covert because they produce damage in the brain without any obvious symptoms. Other research areas of interest are: atherosclerosis, genetics, hypertension and type 2 diabetes mellitus.
Dr. MacIntosh’s research methods rely on blood oxygenation level dependent (BOLD) contrast and arterial spin labeling (ASL) MRI techniques. In BOLD functional MRI (fMRI), we measure changes in the concentration of deoxyhemoglobin while individuals perform a task in the MRI scanner. BOLD-fMRI is the main method for human brain mapping studies. In ASL, water in arterial blood is labeled magnetically and we measure its passage as it travels through arteries, arterioles and capillaries. ASL can be used for brain activation studies as well to produce an image of resting brain perfusion in absolute units of mL/100g of brain tissue/minutes.
Projects:
1.) Physiological consequences of small vessel disease
Small vessel disease (SVD) is a broad term to signify damage that occurs
in the blood vessels in the brain and impacting their role of delivering
nutrients and clearing waste products. SVD can be thought of as accelerated
brain aging and is seen on MRI to reflect the damage to white matter connective
tissue of the brain. SVD is associated with higher risks of stroke and
dementia, but the mechanisms that cause SVD remain a topic of debate. In
this project we look to decompose SVD into the potential sources of disease
by using methods that are sensitive to arteries, capillaries and veins.
2.) Characterizing the effects of carotid endarterectomy surgery
on the brain
Carotid endarterectomy (CEA) is a surgical procedure that is performed
on individuals with significant narrowing of the carotid artery caused
by the build up of atherosclerotic plaque. CEA surgery is used routinely
to reduce the risk of stroke. The purpose of this project is to understand
the short and long-term consequences of the CEA surgery on the brain. We
would like to learn whether functional and physiological MRI will correlate
with certain outcomes, such as silent strokes and/or cognitive dysfunction.
3.) Neurocognitive and cerebrovascular changes in type 2 diabetes
mellitus
The rise in prevalence of type 2 diabetes mellitus is a major concern in
Canada and around the world because of the underlying vascular co-morbid
diseases and the risk of cognitive decline. This is a collaborative project
with colleagues Drs Greenwood and Anderson at Baycrest Hospital. We are
studying how hypertension and type 2 diabetes mellitus impacts the brain
in terms of cognition measures and vascular measures, like cerebrovascular
reactivity, perfusion and intracranial dynamic angiography.
4.) The effects of exercise on the brain
Physical activity and aerobic exercise are associated with numerous health
benefits. Recent studies have shown that aerobic exercise has a direct
effect on the brain by contributing towards positive brain effects like
angiogenesis, neurogenesis and synaptogenesis. Some of the key questions
that remained unanswered is whether exercise can be used as a neurointervention
therapy to augment recovery after injury from stroke. In this project
we are looking at brain metrics like perfusion and resting state fMRI
in conjunction with genetic markers to understand how exercise is able
to have a positive effect on the brain.
Graduate Students:
- A Saeed Rajab
- Ekaterina Tchistiakova
Selected References:
Link to Pubmed Publications-
MacIntosh BJ, Sideso E, Donahue MJ, Chappell MA, Günther M, Handa A, Kennedy J, Jezzard P. Intracranial hemodynamics is altered by carotid artery disease and after endarterectomy: a dynamic magnetic resonance angiography study. Stroke 2011 Apr;42(4):979-84.
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MacIntosh BJ, Filippini N, Chappell MA, Woolrich MW, Mackay CE, Jezzard P. Assessment of Arterial Arrival Times Derived From Multiple Inversion Time Pulsed Arterial Spin Labeling MRI. Magnetic Resonance in Medicine. 2010 Mar;63(3):641-7.
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MacIntosh BJ, Lindsay AC, Kylintireas I, Kuker W, Günther M, Robson MD, Kennedy J, Choudhury RP, Jezzard P. Arterial spin labeling perfusion MRI reveals deficits in minor stroke and transient ischaemic attack. American Journal of Neuroradiology. 2010 31(10):1892-4.
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Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE. Distinct patterns of brain activity in young carriers of the APOE-e4 allele. Proc Natl Acad Sci U S A 2009 106(17):7209-14.
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MacIntosh BJ, Pattinson KT, Gallichan D, Ahmad I, Miller KL, Feinberg DA, Wise RG, Jezzard P. Measuring the effects of remifentanil on cerebral blood flow and arterial arrival time using 3D GRASE MRI with pulsed arterial spin labelling. J Cereb Blood Flow Metab 2008; 28(8):1514-1522.
