Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Bertolo, Adrien; Nouhoum, Mohamed; Cazzanelli, Silvia; Ferrier, Jérémy; Mariani, Jean-Charles; Kliewer, Andrea; Belliard, Benoit; Osmanski, Bruno-Félix; Deffieux, Thomas; Pezet, Sophie; Lenkei, Zsolt; Tanter, Mickaël

doi:10.3791/62267

Cited by 30 publications

(22 citation statements)

References 16 publications

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“…While it would be ideal to image awake and behaving animals with fUS, an advancement currently in development [36,[63][64][65], intact functional connectivity and stimulus responsiveness have been shown using similar dexmedetomidine sedation doses to those used here [26,29]. Furthermore, the effects of anesthesia and heavy sedation have been shown to reduce connectivity, lending more weight to the significance of our results.…”

Section: Limitations and Future Considerationsmentioning

confidence: 69%

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

Grohs-Metz

Smausz

Gigg

et al. 2021

Preprint

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Scientific AbstractEmotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting regional neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, though CeA connectivity was reduced during remote recall. The hippocampus and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable connectivity changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory encoding and retrieval, applicable in the development of innovative treatments for affective disorders.HighlightsFunctional ultrasound imaging can elucidate fear associated neural networksFreezing behavior correlates with cue-evoked functional connectivity changesThe lateral and central amygdalar nuclei are major hubs in the fear networkThe hippocampus is active during recent and remote cued fear memory retrievalConnectivity profiles of the prelimbic and infralimbic areas vary in remote recall

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Section: Limitations and Future Considerationsmentioning

confidence: 69%

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

Grohs-Metz

Smausz

Gigg

et al. 2021

Preprint

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“…1) with 128 ultrasonic transducers and acoustic lens, and a motorized positioning system that allowed for a precise positioning of the probe in three orthogonal planes. The main features, as well as the working principle, are detailed in Bertolo et al [2021]. Briefly, ultrasound imaging exposes part of the body to pulsed ultrasonic waves and displays the amplitude of the ultrasonic echoes backscattered by tissues or fluids.…”

Section: Exposure Systemmentioning

confidence: 99%

In Vivo Functional Ultrasound (fUS) Real‐Time Imaging and Dosimetry of Mice Brain Under Radiofrequency Exposure

Orlacchio

Percherancier

Gannes

et al. 2022

Bioelectromagnetics

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This study aims to analyze in real‐time the potential modifications induced by low‐level continuous‐wave and Global System for Mobile Communications radiofrequency (RF) exposure at 1.8 GHz on brain activation in anesthetized mice. A specific in vivo experimental setup consisting of a dipole antenna for the local exposure of the brain was fully characterized. A unique neuroimaging technique based on a functional ultrasound (fUS) probe was used to observe the areas of mice brain activation simultaneously to the RF exposure with unprecedented spatial and temporal resolution (~100 μm, 1 ms) following manual whisker stimulation using a brush. Numerical and experimental dosimetry was carried out to characterize the exposure and to guarantee the validity of the biological results. Our results show that the fUS probe can be efficiently used during in vivo exposure without interference with the dipole. In addition, we conclude that exposure to brain‐averaged specific absorption rate levels of 2 and 6 W/kg does not introduce significant changes in the time course of the evoked fUS response in the left barrel field cortex. The proposed technique represents a valuable instrument for providing new insights into the possible effects induced on brain activation under RF exposure. For the first time, brain activity under mobile phone exposure was evaluated in vivo with fUS imaging, paving the way for more realistic exposure configurations, i.e. awake mice and new signals such as the 5 G networks. © 2022 Bioelectromagnetics Society.

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“…1 A). They can then perform functional ultrasound acquisition with high frame rate either on a single slice or on several slices 5 , 12 . fUS imaging remains thus inherently limited by the expertise required to neuronavigate oneself within the brain prior to acquisition.…”

Section: Brain Positioning Principlementioning

confidence: 99%

“…Such approach allows high-sensitivity acquisition and to image directly through the skull without complex animal preparation in mice, the most used animal in neuroscience research. Several approaches have been proposed to tackle the challenging whole-brain 3D imaging in fUS, either based on moving linear arrays 5 , matrix arrays 6 , 7 or RCAs (raw column arrays) 8 . However, both matrix arrays and RCAs have limited sensitivity, which is not sufficient to perform transcranial imaging even in mice, and therefore require invasive surgery.…”

Section: Introductionmentioning

confidence: 99%

A functional ultrasound brain GPS for automatic vascular-based neuronavigation

Nouhoum

Ferrier²,

Osmanski³

et al. 2021

Sci Rep

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Recent advances in ultrasound imaging triggered by transmission of ultrafast plane waves have rendered functional ultrasound (fUS) imaging a valuable neuroimaging modality capable of mapping cerebral vascular networks, but also for the indirect capture of neuronal activity with high sensitivity thanks to the neurovascular coupling. However, the expansion of fUS imaging is still limited by the difficulty to identify cerebral structures during experiments based solely on the Doppler images and the shape of the vessels. In order to tackle this challenge, this study introduces the vascular brain positioning system (BPS), a GPS of the brain. The BPS is a whole-brain neuronavigation system based on the on-the-fly automatic alignment of ultrafast ultrasensitive transcranial Power Doppler volumic images to common templates such as the Allen Mouse Brain Common Coordinates Framework. This method relies on the online registration of the complex cerebral vascular fingerprint of the studied animal to a pre-aligned reference vascular atlas, thus allowing rapid matching and identification of brain structures. We quantified the accuracy of the automatic registration using super-resolution vascular images obtained at the microscopic scale using Ultrasound Localization Microscopy and found a positioning error of 44 µm and 96 µm for intra-animal and inter-animal vascular registration, respectively. The proposed BPS approach outperforms the manual vascular landmark recognition performed by expert neuroscientists (inter-annotator errors of 215 µm and 259 µm). Using the online BPS approach coupled with the Allen Atlas, we demonstrated the capability of the system to position itself automatically over chosen anatomical structures and to obtain corresponding functional activation maps even in complex oblique planes. Finally, we show that the system can be used to acquire and estimate functional connectivity matrices automatically. The proposed functional ultrasound on-the-fly neuronavigation approach allows automatic brain navigation and could become a key asset to ensure standardized experiments and protocols for non-expert and expert researchers.

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Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Cited by 30 publications

References 16 publications

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

In Vivo Functional Ultrasound (fUS) Real‐Time Imaging and Dosimetry of Mice Brain Under Radiofrequency Exposure

A functional ultrasound brain GPS for automatic vascular-based neuronavigation

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