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  • Mid-Term Report Summary - SMALLVESSELMRI (Towards understanding cerebral small vessel disease: Innovative, MRI-based, functional markers to discover the terra incognita between large vessels and macroscopic brain lesions)
ERC

SmallVesselMRI Report Summary

Project ID: 337333
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Mid-Term Report Summary - SMALLVESSELMRI (Towards understanding cerebral small vessel disease: Innovative, MRI-based, functional markers to discover the terra incognita between large vessels and macroscopic brain lesions)

Cerebral small vessel disease (SVD) causes 25% of all strokes and is a major cause of cognitive decline, dementia and functional disability in the elderly. Two important challenges hamper the development of effective treatments. First, little is known about the mechanism by which SVD leads to ischemic brain damage and, thus, to cognitive decline. Second, the current clinical markers and image-based markers of SVD do not reflect SVD itself, but macroscopic brain damage secondary to SVD. Unlike large vessels, small vessels are not visible with current imaging techniques, which leave, thus, a ‘terra incognita’ of small vessel pathology between large vessels on the one hand, and macroscopic brain damage on the other. The aim of this research program is to remove the major current obstacle towards developing effective treatments for SVD, by innovative magnetic resonance imaging (MRI) techniques that yield non-invasive markers of small vessel (dys)function in the human brain. Two innovative sets of image-based markers are being developed to discover the ‘terra incognita’.
The first set of image-based markers that is being developed comprises blood flow pulsations in the small arteries and pulsatile tissue motion and strain (driven by the beating vessels). Mechanical strain plays an important role in cell function, including endothelial cells and neurons, and may be altered in cerebral SVD. Moreover, the tissue pulsations also play an important role in the clearance of waste products from the brain. Impaired clearance of waste products is one of the potential mechanisms that may relate SVD to brain tissue damage and amyloid beta accumulation. A method was successfully developed to measure and quantify blood flow velocity and pulsatility with an MRI scanner with an ultra-high magnetic field strength (7 tesla) in the small penetrating arteries of the cerebral white matter in humans. These vessels have diameters comparable to the diameter of human hair. Another developed method (also with 7 tesla MRI), can successfully measure the minute volume change in the brain tissue due to the wave of blood that passes with each heartbeat. This volume change is of the order one tenth of one percent.
The second set of image-based markers hat is being developed aims to use the perivascular fluid as an endogenous marker of how well the brain is able to protect its micro-environment. This micro-environment is protected on one hand by the blood-brain-barrier function, which is located in the endothelium of the small vessels and which prevents substances of entering the brain tissue. On the other hand, a waste clearance system (“glymphatic system”) ensures effective clearance of potentially harmful waste products generated by the brain tissue itself. Changes in the perivascular fluid characteristics on MRI may reflect abnormalities in either the blood-brain-barrier or waste clearance. Quantitative measures are being developed to non-invasively characteristize the perivascular fluid in the human brain.
The currently developed methods are being validated and evaluated in patients with SVD. Thus, more insight in the link between small vessel (dys)function and brain tissue damage might be gained.

Contact

J.J.M. Zwanenburg
Tel.: +31887551394
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Record Number: 189100 / Last updated on: 2016-09-20