Monitoring Drug-Induced Brain Activity Changes with Functional Ultrasound Imaging and Convolutional Neural Networks

Functional ultrasound imaging (fUSI) is a cutting-edge technology that measures changes in cerebral blood volume (CBV) by detecting backscattered echoes from red blood cells moving within its field of view (FOV). It offers high spatiotemporal resolution and sensitivity, allowing for detailed visualization of cerebral blood flow dynamics. While fUSI has been utilized in preclinical drug development studies to explore the mechanisms of action of various drugs targeting the central nervous system, many of these studies have primarily focused on predetermined regions of interest (ROIs). This focus may overlook relevant brain activity outside these specific areas, which could influence the results. To address this limitation, we combined convolutional neural networks (CNNs) with fUSI to comprehensively understand the pharmacokinetic process of Dizocilpine, also known as MK-801, a drug that blocks the N-Methyl-D-aspartate (NMDA) receptor in the central nervous system. CNN and class activation mapping (CAM) revealed the spatiotemporal effects of MK-801, which originated in the cortex and propagated to the hippocampus, demonstrating the ability to detect dynamic drug effects over time. Additionally, CNN and CAM assessed the impact of anesthesia on the spatiotemporal hemodynamics of the brain, revealing no distinct patterns between early and late stages. The integration of fUSI and CNN provides a powerful tool to gain insights into the spatiotemporal dynamics of drug action in the brain. This combination enables a comprehensive and unbiased assessment of drug effects on brain function, potentially accelerating the development of new therapies in neuropharmacological studies.