Biology subjects

Tanter, M.

Publications and source records attributed to Tanter, M..

35 records · Page 2Linked to original sources

bioRxiv2023

Backscattering Amplitude in Ultrasound Localization Microscopy

In the last decade, Ultrafast Ultrasound Localisation Microscopy has taken non-invasive deep vascular imaging down to the microscopic level. By imaging diluted suspensions of circulating microbubbles in the blood stream at kHz framerate and localising the center of their individual point spread function with a sub-resolution precision, it enabled to break the unvanquished trade-off between depth of imaging and resolution by microscopically mapping the microbubbles flux and velocities deep into tissue. However, ULM also suffers limitations. Many small vessels are not visible in the ULM images due to the noise level in areas dimly explored by the microbubbles. Moreover, as the vast majority of studies are performed using 2D imaging, quantification is limited to in-plane velocity or flux measurements which hinders the accurate velocity determination and quantification. Here we show that the backscattering amplitude of each individual microbubble can also be exploited to produce backscattering images of the vascularization with a higher sensitivity compared to conventional ULM images. By providing valuable information about the relative distance of the microbubble to the 2D imaging plane in the out-of-plane direction, backscattering ULM images introduces a physically relevant 3D rendering perception in the vascular maps. It also retrieves the missing information about the out-of-plane motion of microbubbles and provides a way to improve 3D flow and velocity quantification using 2D ULM. These results pave the way to improved visualization and quantification for 2D and 3D ULM.

bioengineering↗

bioRxiv2023

Leptomeningeal collaterals regulate reperfusion in ischemic stroke

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet unknown functions. Utilizing a thrombin-based mouse model of stroke and the gold standard fibrinolytic treatment rt-PA, we here show that LMCs play a critical role in preserving vascular function in ischemic territories. We applied laser speckle contrast imaging, ultrafast ultrasound, and two-photon microscopy, to show that after thrombolysis, LMCs allow for gradual reperfusion resulting in small infarcts. On the contrary, in mice with poor LMCs, distal segments of recanalized arteries collapse and deleterious hyperemia causes hemorrhage and mortality. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for gradual reperfusion of ischemic tissues after stroke.

neuroscience↗

bioRxiv2022

Decoding Motor Plans Using a Closed-Loop Ultrasonic Brain-Machine Interface

Brain-machine interfaces (BMIs) can be transformative for people living with chronic paralysis. BMIs translate brain signals into computer commands, bypassing neurological impairments and enabling people with neurological injury or disease to control computers, robots, and more with nothing but thought. State-of-the-art BMIs have already made this future a reality in limited clinical trials. However, high performance BMIs currently require highly invasive electrodes in the brain. Device degradation limits longevity to about 5 years. Their field of view is small, restricting the number, and type, of applications possible. The next generation of BMI technology should include being longer lasting, less invasive, and scalable to sense activity from large regions of the brain. Functional ultrasound neuroimaging is a recently developed technique that meets these criteria. In this present study, we demonstrate the first online, closed-loop ultrasonic brain-machine interface. We used 2 Hz real-time functional ultrasound to measure the neurovascular activity of the posterior parietal cortex in two nonhuman primates (NHPs) as they performed memory-guided movements. We streamed neural signals into a classifier to predict the intended movement direction. These predictions controlled a behavioral task in real-time while the NHP did not produce overt movements. Both NHPs quickly succeeded in controlling up to eight independent directions using the BMI. Furthermore, we present a simple method to "pretrain" the BMI using data from previous sessions. This enables the BMI to work immediately from the start of a session without acquiring extensive additional training data. This work establishes, for the first time, the feasibility of an ultrasonic BMI and prepares for future work on a next generation of minimally invasive BMIs that can restore function to patients with neurological, physical, or even psychiatric impairments.

neuroscience↗

bioRxiv2022

Specific and non-uniform brain states during cold perception in mice

The quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamo-cortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of awake and freely-moving mice using Functional Ultrasound imaging during plantar exposure to constant and varying temperatures. Our study, a synchronous large field investigation of mice brains reveals for the first time the brain states and the specific dynamic interplay between key regions involved in thermal processing. Our study reveals: i) a dichotomy in the response of the somato-motor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. ii) We infer that cingulate areas may be involved in the affective responses to temperature changes. iii) Colder temperatures (ramped down) reinforces the disconnection between the somato-motor-cingulate and hypothalamus networks. iv) Finally, we also confirm the existence in the mouse brain of a dynamic brain mode characterized by low cognitive strength, described previously only in non-human primates and humans. The present study points towards the existence of a common hub between somato-motor and cingulate regions, whereas hypothalamus functions are related to a secondary network.

neuroscience↗

bioRxiv2022

Covariations of cerebral blood volume and single neurons discharge during resting state and behavioral visual cognitive tasks in non-human primates

To better understand how the brain allows primates to perform various set of tasks, the ability to simultaneously record the activity of the brain at multiple temporal and spatial scales is challenging but necessary. In non-human primates, combined fMRI and electrophysiological recordings have not disentangle the contributions of spiking activity to the neurovascular response. Here, we combined functional ultrasound imaging (fUS) of cerebral blood volume (CBV) and recording of single-unit activities (SUA) in visual and fronto-medial cortices of behaving macaques. We computed task-induced and SUA-induced CBV activation maps. We demonstrate that SUA provides a significant estimate of the neurovascular response below the typical fMRI voxel spatial resolution of 2mm3. Furthermore, our results also show that single unit and CBV activities are statistically uncorrelated during the resting states but correlate during behaving tasks. Conversely, during the resting states, CBV activities across known connected brain areas are correlated but decorrelate at the onset of the tasks as expected if participating in the default mode network (DMN). These results have important implications for interpreting functional imaging findings collected with fMRI or fUS while one constructs inferences of spiking activities during resting-state or while primates perform tasks.

neuroscience↗

bioRxiv2021

Sonogenetic stimulation of the brain at a spatiotemporal resolution suitable for vision restoration

Remote, precisely controlled activation of the brain is a fundamental challenge in the development of brain-machine interfaces providing feasible rehabilitation strategies for neurological disorders. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain1-7, but this approach lacks spatial resolution and cellular selectivity and loads the brain with high levels of acoustic energy. The combination of the expression of ultrasound-sensitive proteins with ultrasound stimulation ( sonogenetic stimulation) can provide cellular selectivity and higher sensitivity, but such strategies have been subject to severe limitations in terms of spatiotemporal resolution in vivo8-10, precluding their use for real-life applications. We used the expression of large-conductance mechanosensitive ion channels (MscL) with high-frequency ultrasonic stimulation for a duration of milliseconds to activate neurons selectively at a relatively high spatiotemporal resolution in the rat retina ex vivo and the primary visual cortex of rodents in vivo. This spatiotemporal resolution was achieved at low energy levels associated with negligible tissue heating and far below those leading to complications in ultrasound neuromodulation6,11. We showed, in an associative learning test, that sonogenetic stimulation of the visual cortex generated light perception. Our findings demonstrate that sonogenetic stimulation is compatible with millisecond pattern presentation for visual restoration at the cortical level. They represent a step towards the precise transfer of information over large distances to the cortical and subcortical regions of the brain via an approach less invasive than that associated with current brain-machine interfaces and with a wide range of applications in neurological disorders.

neuroscience↗

bioRxiv2021

Volumetric ultrasound localization microscopy of the whole brain microvasculature

Technologies to visualize whole organs across scales in vivo are essential for our understanding of biology in health and disease. To date, only post-mortem techniques such as perfused computed tomography scanning or optical microscopy of cleared tissues achieve cellular resolution across entire organs and imaging methods with equal performance in living mammalian organs have yet to be developed. Recently, 2D ultrasound localization microscopy has successfully mapped the fine-scale vasculature of various organs down to a 10 m precision. However, reprojection issues and out-of-plane motion prevent complex blood flow quantification and fast volumetric imaging of whole organs. Here, we demonstrate for the first time in vivo volumetric ultrasound localization microscopy mapping of the rodent brain vasculature. We developed a complete methodological pipeline that includes specific surgery, a dedicated 3D ultrasound acquisition sequence, localization and tracking algorithms, motion correction and realignment, as well as the post-processing quantification of cerebral blood flow. We illustrate the power of this approach, by mapping the whole rat brain vasculature at a resolution of 12 m, revealing mesoscopic to macroscopic vascular architectures and cerebral blood flows ranging from 1 to 100 mm/s. Our results pave the way to the investigation of in vivo vascular processes across the mammalian brain in health and disease, in a wide range of contexts and models.

bioengineering↗

bioRxiv2021

Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC); this rare type of leukodystrophy is characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes (PvAPs, which along with blood vessels form the gliovascular unit (GVU)). We analyzed the GVU in the Mlc1 knock-out mouse model of MLC. The absence of MLC1 led to an accumulation of fluid in the brain but did not modify the endothelial organization or the integrity of the blood-brain barrier. From P10 onward, the postnatal acquisition of vascular smooth muscle cell contractility was altered, resulting in a marked reduction in arterial perfusion and neurovascular coupling. These anomalies were correlated with alterations in astrocyte morphology, astrocyte polarity and the structural organization of the PvAPs perivascular coverage, and poor intraparenchymal circulation of the cerebrospinal fluid (CSF). Hence, MLC1 is required for the postnatal development and organization of PvAPs and controls vessel contractility and intraparenchymal interstitial fluid clearance. Our data suggest that (i) MLC is a developmental disorder of the GVU, and (ii) PvAP and VSMC maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.

neuroscience↗

bioRxiv2021

Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex

Optogenetic stimulation of the primary visual cortex (V1) is a promising therapy for sight restoration, but it remains unclear what total cerebral volume is activated after surface stimulation. In this study, we expressed the red-shifted opsin ChrimsonR in excitatory neurons within V1 in rats, and used the fine spatial resolution provided by functional ultrasound imaging (fUS) over the whole depth of the brain to investigate the brain response to focal surface stimulation. We observed optogenetic activation of a high proportion of the volume of V1. Extracellular recordings confirmed the neuronal origin of this activation. Moreover, neuronal responses were even located in deep layers under conditions of low irradiance, spreading to the LGN and V2, consistent with a normal visual information process. This study paves the way for the use of optogenetics for cortical therapies, and highlights the value of coupling fUS with optogenetics.

neuroscience↗

bioRxiv2021

The Supplementary Eye Field Tracks Cognitive Efforts

Pupil dilation is known to be an index of cognitive effort. Nevertheless, our lack of knowledge of the precise dynamics through which pupil size and activity of the medial prefrontal cortex are conjugated during cognitive tasks highlights the need for its further investigation before, during, and after changes in pupil size. Here, we tested whether pupil dynamics are related to the activity of the supplementary eye field (SEF) during a mixed pro/anti-saccade oculomotor task in two macaque monkeys. We used functional ultrasound imaging (fUS) to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution in relation to behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized CBV responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which anti-saccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward and cognitive effort. These results demonstrate that the SEF is an underestimated but pivotal cortical area for the monitoring and implementation of cognitive effort signals.

neuroscience↗

bioRxiv2020

Single Trial Decoding of Movement Intentions Using Functional Ultrasound Neuroimaging

Brain-machine interfaces (BMI) are powerful devices for restoring function to people living with paralysis. Leveraging significant advances in neurorecording technology, computational power, and understanding of the underlying neural signals, BMI have enabled severely paralyzed patients to control external devices, such as computers and robotic limbs. However, high-performance BMI currently require highly invasive recording techniques, and are thus only available to niche populations. Here, we show that a minimally invasive neuroimaging approach based on functional ultrasound (fUS) imaging can be used to detect and decode movement intention signals usable for BMI. We trained non-human primates to perform memory-guided movements while using epidural fUS imaging to record changes in cerebral blood volume from the posterior parietal cortex - a brain area important for spatial perception, multisensory integration, and movement planning. Using hemodynamic signals acquired during movement planning, we classified left-cued vs. right-cued movements, establishing the feasibility of ultrasonic BMI. These results demonstrate the ability of fUS-based neural interfaces to take advantage of the excellent spatiotemporal resolution, sensitivity, and field of view of ultrasound without breaching the dura or physically penetrating brain tissue.

neuroscience↗

bioRxiv2020

Online modulation of brain hemodynamics despite stereotyped running

Theta and gamma rhythms coordinate large cell assemblies during locomotion. Their spread across temporal and spatial scales makes them challenging to observe. Additionally, the metabolic cost of these oscillations and their contribution to neuroimaging signals remains elusive. To finely characterize neurovascular interactions in running rats, we monitored brain hemodynamics with functional ultrasound and hippocampal local field potentials in running rats. Theta rhythm and running speed were strongly coupled to brain hemodynamics in multiple structures, with delays ranging from 0.8 seconds to 1.8 seconds. Surprisingly, hemodynamics was also strongly modulated across trials within the same recording session: cortical hemodynamics sharply decreased after 5-10 runs, while hippocampal hemodynamics strongly and linearly potentiated, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant, and was accompanied by increased power in hippocampal high-frequency oscillations (100-150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong adaptation processes despite stereotyped behavior.

neuroscience↗

bioRxiv2019

Acoustic biomolecules enhance hemodynamic functional ultrasound imaging of neural activity

Hemodynamic functional ultrasound imaging (fUS) of neural activity provides a unique combination of spatial coverage, spatiotemporal resolution and compatibility with freely moving animals. However, deep and transcranial monitoring of brain activity and the imaging of dynamics in slow-flowing blood vessels remains challenging. To enhance fUS capabilities, we introduce biomolecular hemodynamic enhancers based on gas vesicles (GVs), genetically encodable ultrasound contrast agents derived from buoyant photosynthetic microorganisms. We show that intravenously infused GVs enhance ultrafast Doppler ultrasound contrast and visually-evoked hemodynamic contrast in transcranial fUS of the mouse brain. This hemodynamic contrast enhancement is smoother than that provided by conventional microbubbles, allowing GVs to more reliably amplify neuroimaging signals.

neuroscience↗

bioRxiv2019

Functional ultrasound imaging of deep visual cortex in awake non-human primates

Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed functional Ultrasound (fUS) imaging fUS imaging technique to uncover deep hemodynamic functional responses. Applying fUS imaging on two awake non-human primates performing a passive fixation task, we reconstructed their retinotopic maps down to the deep calcarine and lunate sulci on visual areas (V1, V2 and V3). These maps were acquired in a single hour session with very few stimuli presentation. The spatial resolution of the technology is illustrated by mapping of Ocular Dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions showed that OD selectivity is mostly present in layer IV but with evidence also in layers II/III and V. The fUS imaging technology therefore provides a new mesoscale approach to map brain activities at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.

neuroscience↗

bioRxiv2018

Ultrasound functional neuroimaging reveals propagation of task-related brain activity in behaving primates

In recent decades, neuroimaging has played an invaluable role in improving the fundamental understanding of the brain. At the macro scale, neuroimaging modalities such as MRI, EEG, and MEG, exploit a wide field of view to explore the brain as a global network of interacting regions. However, this comes at the price of either limited spatiotemporal resolution or limited sensitivity. At the micro scale, electrophysiology is used to explore the dynamic aspects of neuronal activity with a very high temporal resolution. However, this modality requires a statistical averaging of several tens of single task responses. A large-scale neuroimaging modality of sufficient spatial and temporal resolution and sensitivity to study brain region activation dynamically would open new territories of possibility in neuroscience\n\nWe show that neurofunctional ultrasound imaging (fUS) is both able to assess brain activation during single cognitive tasks within superficial and deeper areas of the frontal cortex areas, and image the directional propagation of information within and between these regions. Equipped with an fUS device, two macaque rhesus monkeys were instructed before a stimulus appeared to rest (fixation) or to look towards (saccade) or away (antisaccade) from a stimulus. Our results identified an abrupt transient change in activity for all acquisitions in the supplementary eye field (SEF) when the animals were required to change a rule regarding the task cued by a stimulus. Simultaneous imaging in the 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 animals S and Y, respectively. These results provide initial evidence that recording cerebral hemodynamics over large brain areas at a high spatiotemporal resolution and sensitivity with neurofunctional ultrasound can reveal instantaneous monitoring of endogenous brain signals and behavior.

animal behavior and cognition↗

bioRxiv2018

Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier

We demonstrate the feasibility of non-invasively modulating the visual cortex activity of non-human primates by local ultrasound-induced delivery of an inhibitory neurotransmitter (GABA). GABA was injected intravenously after the blood brain barrier (BBB) was transiently disrupted with focused ultrasound (FUS) coupled with ultrasound contrast agents (UCA). Visual evoked potentials exhibited a significant and progressive decrease of the activity. Combined effects of neuromodulation and BBB opening were shown to be 8.7 times less important than GABA-induced inhibition. During the sonication, the UCA harmonic response was monitored to estimate the level of stable cavitation (signature of BBB opening efficiency) and to avoid damages due to inertial cavitation (automatic shutdown of the sonication when detected). As recent developments in beam forming have shown that ultrasound beams can be focused non-invasively in deep-seated human brain locations, our results hold promise to explore and treat the brain with a non-invasive, controllable, repeatable and reversible method.

neuroscience↗

bioRxiv2018

Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret

A major challenge in neuroscience is to longitudinally monitor whole brain activity across multiple spatial scales in the same animal. Functional UltraSound (fUS) is an emerging technology that offers images of cerebral blood volume over large brain portions. Here we show for the first time its capability to resolve the functional organization of sensory systems at multiple scales in awake animals, both within structures by precisely mapping sensory responses, and between structures by elucidating the connectivity scheme of top-down projections. We demonstrate that fUS provides stable (over days), yet rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake ferrets, with unprecedented sharp functional resolution (100m). This was performed in four different brain regions, including small (1-2mm3 size), subcortical (8mm deep) and previously undescribed structures in the ferret. Furthermore, we used fUS to map longdistance projections from frontal cortex, a key source of sensory response modulation, to auditory cortex.

neuroscience↗