Functional Ultrasound Imaging Combined with Machine Learning for Whole-Brain Analysis of Drug-Induced Hemodynamic Changes

TL;DR

This study combines functional ultrasound imaging with machine learning, especially CNNs, to analyze whole-brain hemodynamic responses to drugs, enabling detailed, data-driven regional mapping of pharmacological effects.

Contribution

It introduces a novel framework integrating fUSI with CNNs for comprehensive, whole-brain analysis of drug effects, surpassing ROI-based limitations.

Findings

CNN outperforms SVM and ViT in classifying drug vs. control conditions.

Brain regions like prefrontal cortex and hippocampus are identified as significantly affected.

The approach maintains anatomical specificity while analyzing whole-brain data.

Abstract

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 rely 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 compared three machine learning approaches-convolutional neural network (CNN), support vector machine (SVM), and vision transformer (ViT)-combined with fUSI to analyze the pharmacodynamics of Dizocilpine (MK-801), a potent non-competitive NMDA receptor antagonist commonly used in preclinical models for memory and learning impairments. While all three machine learning techniques could distinguish between drug and control conditions, CNN proved particularly effective due to their ability to capture hierarchical spatial features while maintaining anatomical specificity. Class activation mapping revealed brain regions, including the prefrontal cortex and hippocampus, that are significantly affected by drug administration, consistent with the literature reporting a high density of NMDA receptors in these areas. Overall, the combination of fUSI and CNN creates a novel analytical framework for examining pharmacological mechanisms, allowing for data-driven identification and regional mapping of drug effects while preserving anatomical context and physiological relevance.