Grant: Project Grant

There were an estimated 46.8 million people worldwide living with dementia in 2015, and this number is expected to double every 20 years, at enormous cost to patients, caregivers, and healthcare systems. Dementia is a major manifestation of cerebrovascular disease. For instance, as we age, our blood vessels stiffen and enable the propagation of pulse waves (i.e., pulsatility) into deeper structures of the brain. We think that this pulsatility could cause damage in the brain and eventually lead to dementia. However, mapping pulsatility in small vessels in the brain remains a major technological challenge in small animals and in humans. Blood vessel imaging using ultrasound has undergone multiple breakthrough innovations over the past 10 years. In particular, a recent novel technique drastically improved spatial resolution of blood vessels images, by the detection of millions of individual microbubbles (approved for human use) injected in the blood stream. In recent work, we introduced two critical innovations to this technique: the capability to perform imaging in vivo in 1) three dimensions and 2) dynamically (in other words, movies). Together, these innovations have enabled Dynamic Ultrasound Localization Pulsatility Imaging (DULPI) in entire rodent brains in vessels as small as 20 microns in diameter. The long-term objective of this proposal is to further develop and optimize DULPI to 1) enable the robust and validated imaging of the angioarchitecture and pulsatility of the microvasculature in entire dementia animal model brains and 2) apply it clinically for the development of novel biomarkers of dementia. Should the results of this study indicate high reliability of the DULPI findings, this novel imaging system could be readily applied in pre-clinical settings for fundamental studies, and in a clinical setting for the detection of abnormality and, potentially, treatment guidance.