Funded Projects

Ultrasound is emerging as a powerful, noninvasive method to affect human brain function. However, the effects of ultrasound on neuronal and vascular tissue in the brain are poorly understood. This limits the ability to harness the noninvasive ultrasound in basic neuroscience or human therapies. We propose to explore the mechanisms through both thermal and mechanical effects. Our proposal is based on the demonstration by Dr. Pralle that neurons in the brain can be modulated thermally using magnetic nanoparticles, and on the work of Dr. Bae on mechanical activation of the piezo1/2 channels and phosphoinositide signaling. Dr. Xia will contribute his expertise and resources in ultrasound instrumentation and physics. Dr. Dutta completes the team with his expertise in cerebrovascular medicine and neural engineering. In Aim 1, we propose to explore thermal effects of high-frequency ultrasound (4-8 MHz) to activate TRPV1 and TREK1 ion-channels in cell cultures and to develop ultrasound tools to cause a local temperature increase in the brain through the skull. In Aim 2, we propose to explore the mechanical effects of pulsed lower frequency ultrasound (100s kHz) to activate piezo1/2 channels and phosphoinositide signaling. For both aims, we will develop ultrasound tools and computational models to deliver the required energy into the brain through the skull. By the end of this pilot project, we will have preliminary data to support the mechanistic understanding of ultrasound stimulation. This preliminary data will be the backbone for federal research grant applications. This proposal is different from currently/past funded projects from each PI (Bae: vascular cell/tissue mechanobiology; Dutta: neuroimaging-guided head modeling; Pralle: magnetothermal neuronal research; and Xia: photoacoustic neural imaging) and the team has never collaborated to solve this puzzle through a joint effort.