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Tanter, M.

Publications and source records attributed to Tanter, M..

At least 19 recordsLinked to original sources

SVD-SN2N: Self-Inspired Noise2Noise Learning for Denoising Log-Compressed SVD-Filtered Ultrasound Imaging

Singular value decomposition (SVD) is the reference clutter rejection strategy for medical ultrafast ultrasound imaging, yet SVD filtered images retain a residual noise floor that obscures microvascular signals at depth. Supervised denoising cannot address this gap because clean references do not exist, and most physics-based alternatives require radio-frequency or in-phase/quadrature data that clinical scanners do not expose. We introduce SVD SN2N, a self supervised Noise2Noise framework that operates entirely on the post SVD image and requires neither clean targets nor channel level access. Our central contribution is to show that the residual fluctuations of SVD filtered images are dominated by multiplicative speckle, which violates the zero mean additive assumption of Noise2Noise theory, and that a single log compression step converts it into an additive perturbation whose variance no longer depends on the signal, restoring the conditions the framework requires. The log compressed image is split into two statistically independent half size copies by diagonal 2 times 2 resampling, rescaled by Fourier zero padding interpolation, and used to train a U Net under a self constrained twin-prediction loss. We assess the underlying assumptions directly by measuring the residual noise distribution, its spatial correlation and the signal similarity within diagonal pixel pairs, and we validate the framework on four heterogeneous datasets spanning preclinical and clinical, contrast enhanced and contrast-free, and 2D to 3D regimes. Relative to conventional SVD, SVD SN2N raises image derived SNR by 4.2 to10.6 dB and narrows the apparent vessel full width at half maximum by 34% to 59%, providing a post SVD denoising front end compatible with the image only data available on clinical scanners.

bioengineering↗

Contrast-Free Microvascular and Functional Brain Imaging by Sparse Deconvolution of Ultrafast Power Doppler

Ultrafast power Doppler imaging combined with singular value decomposition (SVD) clutter filtering has become a standard approach for label-free microvascular ultrasound, enabling the visualization of small vessels without microbubble contrast agents. In the absence of contrast, however, SVD filtered Doppler images remain limited by the blur of the imaging system point spread function (PSF) and by a residual noise floor that reduces sensitivity at depth, which together hinder the resolution of fine microvasculature. Here we establish a sparse deconvolution framework to SVD filtered ultrafast power Doppler images. Each Doppler frame is processed in two cascaded stages: a Split-Bregman optimization that solves a regularized least-squares problem combining a sparsity prior and a Hessian continuity prior, followed by an accelerated Richardson Lucy deconvolution with an estimated system PSF. We first validated the framework on a simulation phantom with known ground truth, and then evaluated the framework on in vivo rat-brain plane-wave acquisitions obtained with a Verasonics Vantage system and a 15-MHz linear array. Compared to conventional SVD power Doppler, sparse deconvolution improved the resolution by around 4 and 8 times to lambda/2 and lambda/4, in the lateral and axial directions respectively. We further show that decomposing the Doppler signal into velocity bands before deconvolution disentangles slow and fast flow and yields a velocity-resolved microvascular map. Finally, applying the same framework to task-evoked functional ultrasound, we show that sparse deconvolution preserves the stimulus-locked cerebral-blood-volume response measured by conventional functional ultrasound while sharpening the corresponding activation map from a diffuse cortical region to discrete penetrating vessels. These results indicate that the sparsity-prior super-resolution principles established in label-free ultrafast Doppler ultrasound, and that sparse deconvolution can serve as a practical, contrast-free post-processing front-end for super-resolution microvascular and functional imaging.

bioengineering↗

From Functional Organization to Vascular Structure in the Primate Visual Cortex Using Ultrasound Imaging

The primary visual cortex (V1) provides an exceptional structure to assess information encoding in the cortex thanks to its highly controlled visual input. However, optical measures and electrophysiology are limited to very superficial layers while fMRI provides low spatial resolution. Taking advantages of functional ultrasound imaging (fUSi), we examined large volumes of V1 in two awake non-human primates. We showed the conservation of retinotopic maps within deep sulcal regions and across cortical layers. We then assessed the cortical point image and compared it to its vasculature distribution through ultrasound localization microscopy (ULM). We further identified the smallest vascular compartment underlying the signal. Together, these results establish fUSi, complemented by ULM, as a minimally invasive mesoscale approach for resolving functional organization of the cortex in deep sulci.

neuroscience↗

Multi-Stage Singular Value Decomposition for Ultrafast Ultrasound Imaging of Microbubbles

Microbubble contrast-enhanced ultrasound (CEUS) relies on discriminating nonlinear bubble signals from linear tissue backscattering. While Singular Value Decomposition (SVD) filtering improves this discrimination, existing techniques often fail to retain the slowly-moving microbubble signals from static clutter. Here, we present a novel multi-stage singular value decomposition (MS-SVD) framework for ultrafast CEUS imaging. Our method employs plane-wave transmissions at multiple angles and acoustic pressure levels (implemented via duty-cycle modulation) and alternating transmit polarity. The beamformed data are then processed by three sequential SVD filters: (1) spatial-angular SVD to extract coherent signals across all transmit angles, (2) spatial-pressure SVD to separate linear fundamental and nonlinear harmonic components, and (3) spatiotemporal SVD to isolate moving microbubble echoes from tissue clutter. In in vitro flow phantoms and in vivo rat brain through a cranial window, MS-SVD dramatically improves microbubble detection compared to conventional SVD filtering, MS-SVD yields much stronger vascular contrast and suppresses tissue clutter to a greater extent. The resulting power-Doppler and super-resolution maps are notably cleaner and more complete: MS-SVD detects substantially more microbubble events in ULM, revealing finer vessel details and more accurate flow speeds. By capturing the full acoustic signature of microbubbles (both fundamental and harmonic), MS-SVD achieves higher contrast-to-noise and sensitivity in CEUS. These gains make it a powerful front-end for super-resolution ultrasound localization microscopy and other high-sensitivity microvascular imaging applications.

bioengineering↗

Temporal Patterns of Brain Network Plasticity During the Onset and Maintenance of Neuropathic Pain in Male Mice

Neuropathic pain arises from complex peripheral and central mechanisms and induces long-lasting maladaptive changes in the brain. To investigate the temporal dynamics of these changes, we examined resting-state functional connectivity (FC) in a mouse model of neuropathic pain across its initiation and maintenance phases. Using functional ultrasound imaging to capture whole-brain FC over disease progression, we conducted two complementary studies: a longitudinal assessment in anesthetized animals and an analysis of awake cohorts at distinct disease stages. Both exploratory and literature-guided analyses revealed that FC across most large-scale networks remained remarkably stable during pain maintenance. In contrast, pain onset was marked by enhanced FC between key regions involved in sensory, emotional, and motivational processing, including the motor cortex and nucleus accumbens, the prelimbic and insular cortices, and the infralimbic cortex and hypothalamus. As pain persisted, we observed reduced FC within the somatomotor network, reflecting functional disconnection. Additionally, postsurgical pain alone produced enduring FC changes within the prefrontal cortex, hippocampus, and insula, indicating long-term central plasticity independent of neuropathic injury. Together, these findings reveal dynamic, network-specific adaptations that distinguish the onset and maintenance phases of neuropathic pain and surgery-related plasticity.

neuroscience↗

In vivo microvascular flow quantification in the mouse brain using Row-Column Ultrasound Localization Microscopy and directed graph analysis

Brain perfusion relies on a complex vascular network of arteries, veins, and capillaries to meet its constant demand for oxygen and nutrients. Disruption of this microvascular system is a hallmark of many neurological disorders, including small vessel disease, stroke, and brain tumors. As such, high-resolution in vivo imaging of cerebral microvascular flow and structure remains critical to understanding these pathologies. Among them, Ultrasound Localization Microscopy (ULM) allows noninvasive imaging of microvascular network at subwavelength resolution using injected microbubbles, but the approach remains mainly limited to 2D imaging with few volumetric implementations. In this study, we explore in vivo transcranial 3D ULM of the mouse brain using Row-Column Arrays (RCA) and introduce an analysis framework to build a flow-directed vascular graph from the ULM microbubble tracking data, allowing to differentiate between subgraphs of artery-like and vein-like vascular segments. Combined with Allen-based and Radius-based segmentations, we extract metrics including cerebral blood flow (CBF), microbubble (MB) velocity, flowrate, CBV fraction, vascular segment length and tortuosity in sixty-six different vascular classes. This high-sensitivity framework enables in vivo microvascular imaging and quantification in mice and provides a scalable platform for preclinical neurovascular studies in health and disease.

bioengineering↗

Transcranial in-depth ultrafast ultrasound brain imaging in non-human primates

Ultrasound Localization Microscopy (ULM) offers sub-diffraction resolution vascular imaging by tracking individual contrast microbubbles. However, transcranial implementation in non-human primates remains challenging due to the skulls acoustic attenuation and distortion. This study presents a method for non-invasive transcranial ULM imaging of the anesthetized squirrel monkey through intact skull and skin. We systematically evaluated key ultrasound acquisition parameters and identified an optimal configuration balancing resolution, depth, and vascular representation. Using these refined parameters, we achieved a system resolution of 9.5 {micro}m, measured by Fourier Ring Correlation (FRC), and consistently visualized vessels as small as 23 {micro}m. Full-brain coronal and sagittal acquisitions revealed major vascular landmarks that were reproducible across animals and slices. Importantly, this resolution enables reliable detection of penetrating arterioles and venules, key elements in neurovascular coupling and implicated in various cerebrovascular pathologies. Finally, by tracking microbubbles, we quantified flow velocities from 8.8 to 55 mm/s, corresponding to flow rates ranging from 0.1 to 279 {micro}L/min, demonstrating the techniques ability to access micro- and macrovascular dynamics. This work establishes a framework for high-resolution, non-invasive brain imaging in non-human primates, and opens promising perspectives for studying cerebral structure, function, and dysfunction in translational neuroscience.

neuroscience↗

Harmonic Amplitude-Modulated Singular Value Decomposition for Ultrafast Ultrasound Imaging of Gas Vesicles

Ultrafast nonlinear ultrasound imaging of gas vesicles (GV) contrast agents promises high-sensitivity biomolecular visualization with applications such as targeted molecular imaging of tumor markers or real-time tracking of gene expression. However, separating GV-specific signal from tissue remains challenging and requires the implementation of complex transmit schemes. In this work we introduce harmonic amplitude-modulated singular value decomposition (HAM-SVD), which synergizes pulse inversion (PI) with amplitude-modulated singular value decomposition (AM-SVD) to isolate GV-specific second-harmonic signals. In HAM-SVD, single-cycle plane waves at 9.6 MHz and five tilted angles (at a pulse repetition frequency of 2500 Hz) are transmitted under four duty cycles with alternating polarity. Beamformed IQ data are reshaped along a "space x pressure" matrix and decomposed via SVD; tissue background is cancelled by discarding the first and lowest singular modes, yielding an image comprised solely of pressure-dependent second harmonic signals. HAM-SVD sequence enables wide-field, ultrafast imaging without complex transmit sequences. Validation via simulations, in vitro phantoms, and in vivo rat lower limb experiments demonstrates HAM-SVDs outperformance compared to PI and AM-SVD. HAM-SVD is shown to achieve a 19.16 {+/-} 1.63 dB signal-to-background ratio (SBR) in vivo, surpassing PI (14.19 {+/-} 1.41 dB) and AM-SVD (15.79 {+/-} 1.38 dB). HAM-SVD overcomes limitations of conventional nonlinear techniques (e.g., depth restrictions, tissue clutter) by combining PIs harmonic sensitivity with AM-SVDs adaptive clutter filtering of tissue signals. This approach enhances molecular imaging specificity for GVs and holds potential for ultrasound localization microscopy of slow-flowing agents.

bioengineering↗

Speed Vascular Patterns in the Spatial Navigation System

The hippocampal formation is central to spatial navigation, hosting neurons that encode position, direction, and speed. Yet, the brain-wide vascular dynamics supporting these processes remain poorly understood, especially during naturalistic behaviors. Here, we adapted functional ultrasound (fUS) imaging to examine how cerebral blood volume (CBV) changes relate to behavioral parameters in freely moving rats. High-resolution imaging of hippocampal-parahippocampal regions during open-field exploration reveals strong correlations between CBV dynamics and animal speed, with distinct regional activation patterns and temporal delays. Lagged general linear modeling uncovers information flow from the thalamus to parahippocampal regions, including the medial entorhinal cortex, and to hippocampal subfields (dentate gyrus, CA1-CA3), consistent with a hierarchical processing framework. The analysis also links CBV with angular head speed and the dorsal thalamus. Decoding analyses show that CBV signals not only encode speed precisely but also capture spatial features like proximity to walls and corners, even when univariate analyses do not. This decoding remains robust across animals, underscoring the universality of speed encoding in vascular dynamics. We also identify slow CBV oscillations in the hippocampus aligned with minute-scale speed fluctuations, suggesting a neurovascular signature of exploratory behavior. These findings reveal a hemodynamic signature of speed representation in the navigation system, arising from energy demands in a continuous attractor network model for path integration, where population activity and synaptic currents increase quadratically with animal speed as both peak firing rates and neuronal recruitment scale linearly with animal speed. Moreover, they highlight functional ultrasound imaging as a powerful approach for probing the hemodynamic basis of navigation.

neuroscience↗

Revisiting Free Will: Distributed Activity in the Medial Frontal Cortex Predicts Self-Initiated Action

Research indicates that significant damage to primates medial frontal cortex (MFC) can impede action initiation when anticipating rewards. However, the specific roles within the MFC related to self-generated action preparation remain debated. Here, while two macaques were engaged in an oculomotor task, they occasionally paused and self-resumed the task after varying amounts of time. We utilized the high signal-to-noise ratio from spatial changes in cerebrovascular blood volume (CBV) recorded with ultrafast ultrasound imaging (fUSi) to determine whether the intervals of breaks or the resumption of task-related CBV signals could predict the execution of an ongoing single action. We show that self-initiated eye movements activate the Supplementary eye field (SEF) and the midcingulate cortex (MCC) up to 5.5 seconds before movement execution. Importantly, our results show that a concurrent activity in the SEF and MCC predicts how these two regions might simultaneously exert opposing influences on the voluntary pause and resume of tasks on a single trial basis. The quantification of this dynamic interaction is a novel step for understanding voluntary action in primates and its ability to initiate ones movement based on internal motivations rather than driven, instructed behavior.

neuroscience↗

Transcranial Brain-Wide Functional Ultrasound and Ultrasound Localization Microscopy in Mice using Multilinear Probes

Functional ultrasound imaging (fUS) and ultrasound localization microscopy (ULM) are advanced ultrasound imaging modalities for assessing both functional and anatomical characteristics of the brain. However, the application of these techniques at a whole-brain scale has been limited by technological challenges. While conventional linear acoustic probes provide a narrow 2D field of view and matrix probes lack sufficient sensitivity for 3D transcranial fUS, multilinear probes have been developed to combine high sensitivity to blood flow with fast 3D acquisitions. In this study, we present a novel approach the combined implementation of transcranial whole-brain fUS and ULM in mice using a motorized multilinear probe. This technique provides high-resolution, non-invasive imaging of neurovascular dynamics across the entire brain. Our findings reveal a significant correlation between absolute cerebral blood volume ({Delta}CBV) increases and microbubble velocity, indicating vessel-level dependency of the evoked response. However, the lack of correlation with relative CBV (rCBV) suggests that fUS cannot distinguish functional responses alterations across different arterial vascular compartments. This methodology holds promise for advancing our understanding of neurovascular coupling and could be applied in brain disease diagnostics and therapeutic monitoring.

neuroscience↗

Nonlinear Singular Value Decomposition Beamforming for Ultrasound Imaging of Gas Vesicles

Ultrasound imaging holds significant promise for the observation of molecular and cellular phenomena through the utilization of acoustic contrast agents and acoustic reporter genes. Optimizing imaging methodologies for enhanced detection represents an imperative advancement in this field. Most advanced techniques relying on amplitude modulation scheme such as cross amplitude modulation (xAM) and ultrafast amplitude modulation (uAM) combined with Hadamard encoded multiplane wave transmissions have shown efficacy in capturing acoustic signals of gas vesicles (GVs). Nonetheless, uAM sequence requires odd- or even-element transmissions leading to imprecise amplitude modulation emitting scheme, and the complex multiplane wave transmission scheme inherently yields overlong pulse durations. xAM sequence is limited in terms of field of view and imaging depth. To overcome these limitations, we introduce an innovative ultrafast imaging sequence called nonlinear singular value decomposition (SVD) beamforming. Our method demonstrated a contrast imaging sensitivity comparable to the current gold-standard xAM and uAM, while requiring 4.8 times less pulse transmissions. With similar number of transmit pulses, nonlinear SVD beamforming outperforms xAM and uAM in terms of an improvement in signal-to-background ratio of + 4.78 {+/-} 0.35 dB and + 8.29 {+/-} 3.52 dB respectively. Additionally, our method provides a higher flexibility in terms of the selection of acoustic pressure amplitude compared to the other methods. Furthermore, it shows a significant potential for application in the realm of ultrasound localization microscopy (ULM), where it stands poised to facilitate the more precise extraction of nonlinear signatures originating from contrast agents.

biophysics↗

PhysiofUS : a tissue-motion based method for heart and breathing rate assessment in neurofunctional ultrasound imaging

Recent studies have shown growing evidence that brain function is closely synchronised with global physiological parameters. Heart rate is linked to various cognitive processes and previous research has also demonstrated a strong correlation between neuronal activity and breathing. These findings highlight the significance of monitoring these key physiological parameters during neuroimaging as they provide valuable insights into the overall brain function. Today, in neuroimaging, assessing these parameters required additional cumbersome devices or implanted electrodes. In this work, we performed ultrafast ultrasound imaging both in rodents and human neonates, and we extracted heart and breathing rates from local tissue motion assessed by raw ultrasound data processing. Such PhysiofUS automatically select two specific and optimal brain regions with pulsatile tissue signals to monitor such parameters. We validated the correspondence of these periodic signals with heart and breathing rates assessed using gold-standard electrodes in various conditions in rodents. We also validated Physio-fUS imaging in a clinical environment using conventional ECG. We show the potential of fUS imaging as an integrative tool for simultaneously monitoring physiological parameters during neurofunctional imaging. Beyond the technological improvement, this innovation could enhance our understanding of the link between breathing, heart rate and neurovascular activity both anesthetised in preclinincal research and clinical functional ultrasound imaging.

bioengineering↗

Opioid-Induced Inter-regional Dysconnectivity Correlates with Analgesia in Awake Mouse Brains

The {micro}-opioid receptor (MOP) is crucial for both the therapeutic and addictive effects of opioids. Using a multimodal experimental approach, here we combined awake functional ultrasound (fUS) imaging with behavioral and molecular assessments, to examine opioid-induced changes in brain activation and functional connectivity (FC). Morphine, fentanyl, and methadone induce significant dose- and time-dependent reorganization of brain perfusion, oscillations and FC in awake mice. Notably, opioids induce a transient, region-specific hyperperfusion, followed by a consistent MOP-specific dysconnectivity marked by decreased FC of the somatosensory cortex to hippocampal and thalamic regions, alongside increased subcortical and intra-cortical FC. These FC changes temporally correlate with generalized brain MOP activation and analgesia, but not with hypermobility and respiratory depression, suggesting a reorganization of inter-regional FC as a key opioid effect.

neuroscience↗

Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area of posterior parietal cortex

The lateral intraparietal cortex (LIP) located within the posterior parietal cortex (PPC) is an important area for the transformation of spatial information into accurate saccadic eye movements. Despite extensive research, we do not fully understand the functional anatomy of intended movement directions within LIP. This is in part due to technical challenges. Electrophysiology recordings can only record from small regions of the PPC, while fMRI and other whole-brain techniques lack sufficient spatiotemporal resolution. Here, we use functional ultrasound imaging (fUSI), an emerging technique with high sensitivity, large spatial coverage, and good spatial resolution, to determine how movement direction is encoded across PPC. We used fUSI to record local changes in cerebral blood volume in PPC as two monkeys performed memory-guided saccades to targets throughout their visual field. We then analyzed the distribution of preferred directional response fields within each coronal plane of PPC. Many subregions within LIP demonstrated strong directional tuning that was consistent across several months to years. These mesoscopic maps revealed a highly heterogenous organization within LIP with many small patches of neighboring cortex encoding different directions. LIP had a rough topography where anterior LIP represented more contralateral upward movements and posterior LIP represented more contralateral downward movements. These results address two fundamental gaps in our understanding of LIPs functional organization: the neighborhood organization of patches and the broader organization across LIP. These findings were achieved by tracking the same LIP populations across many months to years and developing mesoscopic maps of direction specificity previously unattainable with fMRI or electrophysiology methods.

neuroscience↗

Development of a novel, non-invasive and whole brain biomarker of demyelination in a mouse model of multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), affecting 2.8 million people worldwide, that presents multiple features, one of which is demyelination. Although treatments exist to manage the condition, no cure has been found to stop the progression of neurodegeneration. To develop new treatments and investigate the multiple systems impacted by MS, new imaging technologies are needed at the preclinical stage. Functional ultrasound imaging (fUS) has recently been demonstrated to robustly measure brain cerebral blood volume (CBV) dynamics as an indirect measure of neural activity. This study aimed at proposing a new biomarker of de- and/or re-myelination in a mouse model of MS induced by cuprizone. We demonstrate first that extended demyelination induces an increased hemodynamic response in the primary sensory cortex both spatially and temporally, which is consistent with fMRI data collected on MS patients. Second, using descriptors of the evoked hemodynamic response, we show that 3 of these descriptors allows the prediction of the level of myelin in the primary sensory cortex (p=5. 10-5) and the thalamus (p=6. 10-6). The development of such a non-invasive biomarker is crucial in the MS field as is provides an extremely useful tool for both disease follow-up and drug development. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSMultiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system. It is the most common cause of neurological disability in young adults, affecting approximately 2.8 million worldwide. While the field of studies in MS has been very active at identifying the neurobiological cellular and molecular mechanisms underlying MS progression, the number of new treatments has been very limited so far, due to several factors, such as the lack of robust and non-invasive biomarkers of myelin loss in longitudinal studies (measurements during the development of the disease). Unfortunately, quantification of myelin loss, (one of the key neurobiological markers of MS progression) is classically performed post-mortem on fixed tissues, preventing longitudinal studies. Longitudinal follow up of an indirect measure of myelin loss is possible, using magnetic resonance imaging. However, the small size of rodent brains poses a challenge for conventional imaging techniques, requiring the use of high field magnet to achieve the necessary sensitivity and resolution. Added value of this studyIn this study, using a sensitive neuroimaging technique, we developed a simple, non-invasive, predictive biomarker able to quantify the individual amount of myelin content consistently and accurately in brain structures in mice. Implications of all the available evidenceThe development of such a biomarker is extremely important for the MS field as it will accelerate the pre-clinical tests for drug efficacy. The benefits provided by our biomarker encompass: 1) Enhanced sensitivity in individually quantifying myelin content, providing a more comprehensive assessment across diverse brain regions 2) Speeding up the process of the discovery, by reducing the number of animals required per group and 3) It will also likely lead to new scientific outcomes, as many more structures will be studied (most teams and drug compagnies only study the demyelination at the level of the corpus callosum). Finally, from a clinical perspective, given the brain alterations observed in this animal model closely mirror those observed in early stages in patients with MS, we anticipate our biomarker, with minimal additional refinements, to be readily applicable in clinical settings.

neuroscience↗

Western diet feeding since adolescence impairs functional hyperemia probed by functional ultrasound imaging at adulthood and middle age: rescue by a balanced ω-3:ω-6 polyunsaturated fatty acids ratio in the diet

Obesity is a devastating worldwide metabolic disease, with the highest prevalence in children and adolescence. Obesity impacts neuronal function but the fate of functional hyperemia, a vital mechanism making possible cerebral blood supply to active brain areas, is unknown in organisms fed a high caloric Western Diet (WD) since adolescence. We mapped changes in cerebral blood volume (CBV) in the somatosensory cortex in response to whiskers stimulation in adolescent, adult and middle-aged mice fed a WD since adolescence. To this aim, we used non-invasive and high-resolution functional ultrasound imaging (fUS). Functional hyperemia is compromised as early as 3 weeks of WD and remains impaired thereafter. Starting WD in adult mice does not trigger the profound impairment in sensory-evoked CBV observed in young mice, suggesting a cerebrovascular vulnerability to WD during adolescence. A balanced {omega}-6:{omega}-3 polyunsaturated fatty acids ratio in WD achieved by docosahexaenoic acid supplementation is efficient to restore glucose homeostasis and functional hyperemia in adults.

neuroscience↗

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A., Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res, 2014. 75(3): p. 376-80). In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery (Luca, A.,et al., Birth trauma in preterm spontaneous vaginal and cesarean section deliveries: A 10-years retrospective study. PloS one,2022, 17(10), e0275726.) We have developed and characterized a mouse model based on intraperitoneal injections of IL-1{beta} between postnatal days one and five to reproduce perinatal systemic inflammation (Favrais, G.,et al., Systemic inflammation disrupts the developmental program of white matter. Ann Neurol,2011. 70(4): p. 550-65). This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1{beta} on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders. Significance StatementIn a well-established mouse model of the encephalopathy of prematurity, we observed that C-section exacerbates the deleterious effects of neonatal systemic inflammation (intraperitoneal injections of IL-1{beta} between postnatal days one and five) on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced brain functional connectivity. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

neuroscience↗