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Fifty million people worldwide are affected by dementia, a heterogeneous neurodegenerative condition encompassing diseases such as Alzheimer's, vascular dementia, and Parkinson's. For them, cognitive decline is often the first marker of the pathology after irreversible brain damage has already occurred. Researchers now believe that structural and functional alterations of the brain vasculature could be early precursors of the diseases and are looking at how functional imaging could provide an early diagnosis years before irreversible clinical symptoms. In this preclinical pilot study, we proposed using functional ultrasound (fUS) on the retina to assess neurovascular alterations non-invasively, bypassing the skull limitation. We demonstrated for the first time the use of functional ultrasound in the retina and applied it to characterize the retinal hemodynamic response function in vivo in rats following a visual stimulus. We then demonstrated that retinal fUS could measure robust neurovascular coupling alterations between wild-type rats and TgF344-AD rat models of Alzheimer's disease. We observed an average relative increase in blood volume of 21% in the WT versus 37% for the TG group (p = 0.019). As a portable, non-invasive and inexpensive technique, rfUS is a promising functional screening tool in clinics for dementia years before symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Sensitivity of contrast-enhanced ultrasound (CEUS) to microvascular flow modifications can be limited by intra-injection variability (injected dose, rate, volume).Procedures: To evaluate the effect of injection variability on microvascular flow evaluation, CEUS was compared between controlled and manual injections where enhancement was assessed in vitro within a flow phantom, in normal murine kidney (N = 12) and in murine ectopic tumors (N = 10).Results: For both in vitro and in vivo measurements in the renal cortex, controlled injections significantly improved reproducibility of functional parameter estimation. Their coefficient of variation (CV) in the renal cortex ranged from 4 to 19 % for controlled injection vs. 5 to 43 % for manual injections. For measurements in tumors, controlled injection only decreased the CV significantly for the mean transit time. In tumors, multiple injections of contrast agent with a 15-min delay between each were shown to strongly modify contrast uptake by facilitating penetration of microbubbles.Conclusion: Improved reproducibility of CEUS assessments in murine models should provide more robust quantification of flow parameters and more sensitive evaluation of tumor modifications in therapeutic models. [ABSTRACT FROM AUTHOR]

Neuroimaging modalities such as MRI and EEG are able to record from the whole brain, but this comes at the price of either limited spatiotemporal resolution or limited sensitivity. Here, we show that functional ultrasound imaging (fUS) of the brain is able to assess local changes in cerebral blood volume during cognitive tasks, with sufficient temporal resolution to measure the directional propagation of signals. In two macaques, we observed an abrupt transient change in supplementary eye field (SEF) activity when animals were required to modify their behaviour associated with a change of saccade tasks. SEF activation could be observed in a single trial, without averaging. Simultaneous imaging of anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for both animals. Cerebral hemodynamics of large brain areas can be measured at high spatiotemporal resolution using fUS. Neuroimaging modalities such as MRI and EEG are able to record brain activity, but spatiotemporal resolution and sensitivity are limited. Here, the authors show how a recently developed method, functional ultrasound imaging (fUS), can measure brain activation during cognitive tasks in primates. [ABSTRACT FROM AUTHOR]