Cerebral Blood Flow (CBF), which is crucial for maintaining energy supply to support synaptic activity, is known to be a strong indicator of brain function. Therefore, CBF, along with other factors, is used to link blood oxygenation signals to cellular activity in the brain.
However, current techniques for measuring CBF in awake animals via imaging face a daunting challenge. They must trade off the depth of the captured image—which gives more information about the volume of blood flowing through a vessel—with the image's resolution, which indicates the velocity of the blood flowing through a vessel. Moreover, most preclinical CBF studies—including the ones studying the effects of cocaine—on animals have been performed under anesthesia, which greatly affects the findings.
In a recent study, Stony Brook University Professor Haibin Ling collaborated with other professors and researchers from the institute, as well as with fellows from the National Institute of Health, to meet these challenges and further advance research in CBF measurement in awake animals. The team performed the experiments themselves, fitting a cranial window on the cortexes of 29 mice, using a customized treadmill to allow for horizontal movement, and training them to reduce movement when awake, so that CBF images could be captured with as few motion artifacts as possible. The team also optimized a flow imaging platform, using self-supervised machine learning to reduce motion artifacts in CBF images significantly.
As a next step, 16 out of the 29 mice were used in experiments to study the effects of cocaine on Cerebral Blood Flow. While it is well known that cocaine misuse increases life-threatening neurological complications (25 to 60% of cases see a restriction of blood vessels in the brain, which gives rise to more problems), there is very little knowledge of the exact effects of cocaine consumption on the cerebrovascular network. The team then compared these images with those of anesthetized cocaine-induced mice, presenting their contributions to the research.
Their findings not only showed that out of the three anesthetics used in these experiments—Iso, Dex, and Ketamine—Dex had the least effect on CBF volume, but also that acute cocaine exposure in awake mice reduces the CBF volume in all blood networks of the brain. While these findings add to the growing literature on the effects of chronic cocaine consumption in awake mice, the 3D imaging platform presented by the team is a powerful tool for studying dynamic changes in CBF volume and greatly advances our understanding of the effects of drugs and disease conditions like ischemia, tumors, and wound healing.
Ankita Nagpal
Communications Assistant