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Functional Ultrasound Imaging System for Neuropharmacology Industry-Medical / Health Care
Functional ultrasound (fUS) imaging is emerging as a powerful tool in neuropharmacology to study the effects of drugs on brain activity. Unlike fMRI, fUS offers increased sensitivity and compatibility with awake animal models, providing an unbiased view of drug interactions with neural substrates. Recent studies by Theranexus have utilized fUS to observe the hemodynamic response to different pharmacological interventions, such as the combination of donepezil and mefloquine, which target acetylcholinesterase inhibitors and connexins respectively. This approach has elucidated changes in cerebral blood volume and functional connectivity between brain regions. Furthermore, fUS aids in establishing pharmacokinetic/pharmacodynamic parameters by examining dose-response relationships and the regional specificity of centrally-acting drugs. The technique provides valuable insights into the central mechanisms of action of drugs, supporting the advancement of treatments for conditions like Alzheimer's and aiding in the understanding of CNS drug efficacy.
In a similar way to fMRI, functional ultrasound can be used in neuropharmacology studies to determine time- and dose-dependent effects of drugs on the brain. But unlike fMRI, this ‘pharmaco-fUS’ approach is more sensitive, faster, more reproducible, and compatible with awake animals (eliminating the bias of anesthesia).
Investigating the effect of drugs on functional connectivity
In this study, it was shown that scopolamine (used preclinically as a model for Alzheimer’s disease) leads to rapid and lasting changes in functional connectivity between the two hemispheres of the hippocampus and the neighboring areas of the cortex.
In this set of seed-based correlation plots, averaged over five mice, a small area of the hippocampus was used as a ‘seed’, and fUS used to reveal correlations during each of seven motion-free time periods (T1–T7). The initial baseline analyses reveal, as expected, a strong inter-hemispheric correlation within the hippocampus. After scopolamine injection, this connection is stronger and more diffuse, with correlations also shown to neighboring cortical areas. Reproduced from Rabut et al., NeuroImage, 2020 (licensed under CC BY 4.0)
Investigating the effect of drugs on changes in cerebral blood volume
The first of these (shown in the figure) found a synergistic brain response between an AChE inhibitor (donepezil) used to alleviate cognitive symptoms in Alzheimer’s disease and a new drug (mefloquine) targeting connexins. Importantly, this fUS study also complements previous work that showed how the drug combination could reverse scopolamine-induced memory loss, by providing detail on the areas affected.
In the second study (Vidal et al., Neuropharmacology, 2020), the effect of atomoxetine (a potent norepinephrine reuptake inhibitor and treatment for ADHD) was investigated in anesthetized rats. A dose-dependent variation of CBV with time was observed, particularly in brain regions involved in vision.