Biology subjects

Brunner, C.

Publications and source records attributed to Brunner, C..

11 recordsLinked to original sources

bioRxiv2025

OfUSA: OpenfUS Analyzer, a versatile open-source framework for the analysis and visualization of functional ultrasound imaging data across animal models

Functional ultrasound (fUS) imaging is rapidly gaining interest for its unprecedented ability to study large-scale brain dynamics, yet its adoption and broader dissemination have been hindered by the lack of standardized tools and methodologies to analyze and interpret its rich datasets. We present OpenfUS Analyzer (OfUSA), a companion software suite designed to help researchers quickly engage with fUS data and perform the full range of analyses needed to generate publication-ready results and figures without relying on additional software. OfUSA offers a versatile and modular architecture including preprocessing, recording quality assessment, signal dynamics exploration, statistical analysis and visualization. These functions are separated yet easily combined into analytic pipelines through a programming-free graphical interface. The framework can be applied across species and experimental contexts, either by registering data to anatomical atlases, as shown here for the mouse brain, or by analyzing data without atlas constraints, as illustrated in a primate dataset. This flexibility, together with its comprehensive functionality, makes OfUSA a practical solution for standardized and reproducible analysis of fUS data in both preclinical and translational research. Using OfUSA, we demonstrate the capacity to detect stimulus-evoked responses with high sensitivity, identify their spatial localization within brain networks, and quantify both their extent and temporal dynamics. These results highlight the softwares ability to capture robust activation patterns and provide detailed insights into brain function, thereby accelerating the use of fUS as a powerful tool for systems neuroscience. HighlightsWe present OpenfUS Analyzer (OfUSA), a novel software platform for the complete analysis of functional ultrasound (fUS) datasets. OfUSA combines a user-friendly graphical interface with a standardized, flexible workflow and powerful visualization tools, making it an ideal solution for fUS researchers at all experience levels. The softwares utility is first demonstrated through the analysis of rodent fUS data using a standardized atlas, while its versatility is further emphasized by the successful analysis of a primate fUS dataset without a template, thereby illustrating its adaptability to non-standard experimental conditions.

neuroscience↗

bioRxiv2025

Continuous monitoring of cerebrovascular autoregulation using functional ultrasound imaging in the piglet brain.

Continuous real-time assessment of cerebral blood flow (CBF) and cerebrovascular autoregulation (CA) remains a major unmet clinical need in acute brain injury. Methods such as laser Doppler flowmetry (LDF), transcranial Doppler, or indirect indices lack accuracy and robustness. Functional ultrasound (fUS) is an emerging modality combining high spatiotemporal resolution, large field-of-view, and sensitivity to blood velocity and volume, making it a promising neuromonitoring tool. Piglets were equipped with arterial blood pressure (ABP), intracranial pressure (ICP), and LDF probes, plus cranial windows for fUS and red blood cell (RBC) flux imaging. CA was challenged by non-pharmacological ABP manipulation via intraaortic or intracaval balloon inflation. fUS hemodynamic parameters were compared with other modaliters across a CPP range of 10-150 mmHg. fUS provided continuous, stable intensity- and velocity-derived parameters across vessels types. CBF estimates correlated strongly with RBC flux and showed reproducibility comparable to LDF, with lower inter-animal variability. Autoregulation breakpoints were reliably identified by fUS, particularly the lower limit, while the upper limit was more variable. Parcellation confirmed robustness of fUS across brain regions. fUS images CBF and CA with higher stability and reproducibility than standard approaches, supporting its applicability for bedside neuromonitoring and clinical translation.

neuroscience↗

bioRxiv2025

Bottom-up investigation of spatiotemporal glycocalyx dynamics with interferometric scattering microscopy

Over recent decades, the glycocalyx, an extracellular organelle comprised of a multitude of glycolipids, glycoproteins, proteoglycans and glycoRNA, has gained considerable interest in cellular biology. While research in this field has revealed its tremendous importance in evermore aspects of physiological and pathological cellular processes, many of the principles that govern the role of the glycocalyx in these processes on a molecular level are still unknown. In order to unravel the fundamental laws underlying glycocalyx function, new technologies are required that enable the distinction between individual subprocesses within the intricate environment of the glycocalyx. Here, we establish an experimental platform to investigate the dynamics of the glycocalyx at the nanometer and microsecond length and time scales in a bottom-up fashion. We synthesized defined model glycans and installed them on supported lipid bilayers, assembling glycocalyx model systems with tunable properties. By investigating these tunable model systems with interferometric scattering (iSCAT) microscopy, we gain access to the required spatiotemporal resolution. We found a strong correlation between the molecular structure of several investigated model glycans and global dynamics of the system. Our findings are corroborated by atomistic and coarsegrained molecular dynamics simulations. Our results provide the first direct experimental evidence on the relationship between glycan structure, organization, and dynamics, offering a robust and versatile basis for a quantitative understanding of glycocalyx biology and physics at the molecular level.

biophysics↗

bioRxiv2024

Functional ultrasound imaging and neuronal activity: how accurate is the spatiotemporal match?

Over the last decade, functional ultrasound (fUS) has risen as a critical tool in functional neuroimaging, leveraging hemodynamic changes to infer neural activity indirectly. Recent studies have established a strong correlation between neural spike rates (SR) and functional ultrasound signals. However, understanding their spatial distribution and variability across different brain areas is required to thoroughly interpret fUS signals. In this regard, we conducted simultaneous fUS imaging and Neuropixels recordings during stimulus-evoked activity in awake mice within three regions the visual pathway. Our findings indicate that the temporal dynamics of fUS and SR signals are linearly correlated, though the correlation coefficients vary among visual regions. Conversely, the spatial correlation between the two signals remains consistent across all regions with a spread of approximately 300 micrometers. Finally, we introduce a model that integrates the spatial and temporal components of the fUS signal, allowing for a more accurate interpretation of fUS images.

neuroscience↗

bioRxiv2023

Functional ultrasound imaging of stroke in awake rats

Anesthesia is a major confounding factor in preclinical stroke research as stroke rarely occurs in sedated patients. Moreover, anesthesia affects both brain functions and the stroke outcome acting as neurotoxic or protective agent. So far, no approaches were well suited to induce stroke while imaging hemodynamics along with simultaneous large-scale recording of brain functions in awake animals. For this reason, the first critical hours following the stroke insult and associated functional alteration remain poorly understood. Here, we present a strategy to investigate both stroke hemodynamics and stroke-induced functional alterations without the confounding effect of anesthesia, i.e., under awake condition. Functional ultrasound (fUS) imaging was used to continuously monitor variations in cerebral blood volume (CBV) in +65 brain regions/hemisphere for up to 3hrs after stroke onset. The focal cortical ischemia was induced using a chemo-thrombotic agent suited for permanent middle cerebral artery occlusion in awake rats, and followed by ipsi- and contralesional whiskers stimulation to investigate on the dynamic of the thalamo-cortical functions. Early (0-3hrs) and delayed (day 5) fUS recording enabled to characterize the features of the ischemia (location, CBV loss), spreading depolarizations (occurrence, amplitude) and functional alteration of the somatosensory thalamo-cortical circuits. Post-stroke thalamo-cortical functions were affected not only early after the stroke onset but were also altered secondarly and remotely from the initial insult. Overall, our procedure enables early, continuous, and chronic evaluations of hemodynamics and brain functions which, combined to stroke or other pathologies, aims to better understand physiopathologies toward the development of clinically relevant therapeutic strategies.

neuroscience↗

bioRxiv2022

Large scale in vivo acquisition, segmentation and 3D reconstruction of cortical vasculature using functional ultrasound imaging.

The brain is composed of a dense and ramified vascular network comprising various sizes of arteries, veins, and capillaries. One way to assess the risk of cerebrovascular pathologies is to use computational models to predict the physiological effects of a reduction of blood supply and correlate these responses with observations of brain damage. Therefore, it is crucial to establish a detailed 3D organization of the brain vasculature, which could be used to develop more accurate in silico models. For this purpose, we have adapted our open-access functional ultrasound imaging platform previously designed for recording brain-wide activity that is now capable of fast and reproducible acquisition, segmentation, and reconstruction of the cortical vasculature. For the first time, it allows us to digitize the cortical vasculature in awake rodents with a [~]100 {micro}m3 spatial resolution. Contrary to most available strategies, our approach can be performed in vivo within minutes. Moreover, it is easy to implement since it neither requires exogenous contrast agents nor long post-processing time. Hence, we performed a cortex-wide reconstruction of the vasculature and its quantitative analysis, including i) classification of descending arteries versus ascending veins in more than 1500 vessels/animal, ii) quick estimation of their length. Importantly, we confirmed the relevance of our approach in a model of cortical stroke, which enables quick visualization of the ischemic lesion. This development contributes to extending the capabilities of ultrasound neuroimaging to understand better cerebrovascular pathologies such as stroke, vascular cognitive impairment, and brain tumors and is highly scalable for the clinic.

neuroscience↗

bioRxiv2022

A deep learning classification task for accurate brain navigation during functional ultrasound imaging

Positioning and navigation are essential components of neuroimaging as they improve the quality and reliability of data acquisition, leading to advances in diagnosis, treatment outcomes, and fundamental understanding of the brain. Functional ultrasound (fUS) imaging is an emerging technology providing high-resolution images of the brain vasculature, allowing for the monitoring of brain activity. However, as the technology is relatively new, there is no standardized tool for inferring the position in the brain from the vascular images. This study presents a deep learning-based framework designed to address this challenge. Our approach uses an image classification task coupled with a regression on the resulting probabilities to determine the position of a single image. We conducted experiments using a dataset of 51 rat brain scans to evaluate its performance. The training positions were extracted at intervals of 375 {micro}m, resulting in a positioning error of 176 {micro}m. Further GradCAM analysis revealed that the predictions were primarily driven by subcortical vascular structures. Finally, we assessed the robustness of our method in a cortical stroke where the brain vasculature is severely impaired. Remarkably, no specific increase in the number of misclassifications was observed, confirming the methods reliability in challenging conditions. Overall, our framework provides accurate and flexible positioning, not relying on a pre-registered reference but on conserved vascular patterns.

neuroscience↗

bioRxiv2022

Brain-wide continuous functional ultrasound imaging for real-time monitoring of hemodynamics during ischemic stroke

Ischemic stroke occurs with no warning, and therefore, very little is known about hemodynamic perturbations in the brain immediately after stroke onset. Here, functional ultrasound imaging was used to monitor variations in relative cerebral blood volume (rCBV) compared to baseline. rCBV levels were analyzed brain-wide and continuously at high spatiotemporal resolution (100m, 2Hz) until 70mins after stroke onset in rats. We compared two stroke models, with either a permanent occlusion of the middle cerebral artery (MCAo) or a tandem occlusion of both the common carotid and middle cerebral arteries (CCAo+MCAo). We observed a typical hemodynamic pattern, including a quick drop of the rCBV after MCAo, followed by spontaneous reperfusion of several brain regions located in the vicinity of the ischemic core. The severity and location of the ischemia were highly variable between animals. Still, both parameters were, on average, in good agreement with the final ischemic lesion volume measured 24hrs after stroke onset for the MCAo but not the CCAo+MCAo model. For the latter, we observed that the infarct was extended to regions that were initially not ischemic and located rostrally of the ischemic core. These regions strongly colocalize with the origin of transient hemodynamic events associated with spreading depolarizations.

neuroscience↗

bioRxiv2020

Fact retrieval or compacted procedures in arithmetic - a neurophysiological investigation of two hypotheses

There is broad consensus that adults solve single-digit multiplication problems almost exclusively by fact retrieval (i.e., retrieval of the solution from an arithmetic fact network). In contrast, there has been a long-standing debate on the cognitive processes involved in solving single-digit addition problems. This debate has evolved around two theoretical accounts. The fact-retrieval account postulates that these are solved through fact retrieval, just like multiplications, whereas the compacted-procedure account proposes that solving very small additions (i.e., problems with operands between 1 and 4) involves highly automatized and unconscious compacted procedures. In the present electroencephalography (EEG) study, we put these two accounts to the test by comparing neurophysiological correlates of solving very small additions and multiplications. A sample of 40 adults worked on an arithmetic production task involving all (non-tie) single-digit additions and multiplications. Afterwards, participants completed trial-by-trial strategy self-reports. In our EEG analyses, we focused on induced activity (event-related synchronization/desynchronization, ERS/ERD) in three frequency bands (theta, lower alpha, upper alpha). Across all frequency bands, we found higher evidential strength for similar rather than different neurophysiological processes accompanying the solution of very small addition and multiplication problems. This was also true when n + 1 and n x 1 problems were excluded from the analyses. In two additional analyses, we showed that ERS/ERD can differentiate between self-reported problem-solving strategies (retrieval vs. procedure) and even between n + 1 and n + m problems in very small additions, demonstrating its high sensitivity to cognitive processes in arithmetic. The present findings clearly support the fact-retrieval account, suggesting that both very small additions and multiplications are solved through fact retrieval. HIGHLIGHTSO_LINeurophysiological test of fact retrieval and compacted procedures account C_LIO_LIInduced EEG data are sensitive to cognitive processes in arithmetic problem solving C_LIO_LIBoth very small additions and multiplications are solved through fact retrieval C_LI

neuroscience↗

bioRxiv2018

Electrochemotherapy with bleomycin associated with doxorubicin induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinomas

Canine cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer in dogs, and due to its low metastatic rate, local treatments such as electrochemotherapy (ECT) promote disease control or even complete remission and increase the survival time in most cases. This study aimed to evaluate the expression of BAX, Bcl-2, and Ki67 and clinical parameters in dogs with cSCC subjected to ECT. A prospective clinical nonrandomized study was performed in dogs with naturally occurring cSCC treated with ECT. Eighteen lesions (from 11 dogs) were selected, independent of breed, sex and age. The ECT protocol consisted of bleomycin plus doxorubicin followed by electric pulses characterized by 8 biphasic electric pulses lasting 100 ms, 1 Hz and 1000 V/cm. Among the 18 lesions, the lesion volume significantly decreased after treatment (p=0.04). The tumor size at D0 had no impact on survival time or prognosis (P>0.05). A decreased mitotic index was observed at compared with D0 (P=0.019). We also observed more intratumoral necrosis at D21 compared to D0 (P=0.041). The median expression level of Ki67 was 277.96 at D0 and 193.92 at D21. Thus, tumor samples had a lower proliferative index after ECT (D21) (P=0.031). The survival times of subjects with Ki67 values lower and higher than the Ki67 median value were not significantly different (P>0.05). Regarding apoptotic markers, there was no significant difference in BAX or Bcl-2 expression between D0 and D21 (P>0.05) or in overall survival between subjects with different levels of apoptotic markers. Furthermore, a positive correlation was observed between BAX and Bcl-2 before ECT (D0) (P=0.0379, r=0.5067). In conclusion, there was no change in BAX and Bcl-2 protein expression levels in response to ECT at the time points evaluated, and ECT was able to reduce tumor volume and cellular proliferation in cSCC.

cancer biology↗

bioRxiv2018

MRI-related anxiety in healthy individuals, intrinsic BOLD oscillations at 0.1 Hz and heart rate variability in low frequency bands

Participation in a MRI scan is associated with increased anxiety, thus possibly impacting baseline recording for functional MRI studies. We investigated in 23 healthy individuals without any former MRI experience (scanner-naive) the relations between anxiety, 0.1-Hz BOLD oscillations and heart rate variability (HRV) in two separate resting state sessions (R1, R2). BOLD signals were recorded from precentral gyrus (PCG) and insula in both hemispheres. Phase-locking and time delays were computed in the frequency band 0.07-0.13 Hz. Positive (pTD) and negative time delays (nTD) were found. The pTD characterize descending neural BOLD oscillations spreading from PCG to insula and nTD characterize ascending vascular BOLD oscillations related to blood flow in the middle cerebral artery. HRV power in two low frequency bands 0.06-0.1 Hz and 0.1-0.14 Hz was computed. Based on the drop rate of the anxiety level from R1 to R2, two groups could be identified: one with a strong anxiety decline (large drop group) and one with a moderate decline or even anxiety increase (small drop group). A significant correlation was found only between the left-hemispheric time delay (pTD, nTD) of BOLD oscillations and anxiety drop, with a dominance of nTD in the large drop group. The analysis of within-scanner HRV revealed a pronounced increase of low frequency power between both resting states, dominant in the band 0.06-0.1 Hz in the large drop group and in the band 0.1-0.14 Hz in the small drop group. These results suggest different mechanisms related to anxiety processing in healthy individuals. One mechanism (large drop group) could embrace an increase of blood circulation in the territory of the left middle cerebral artery (vascular BOLD) and another (small drop group) translates to rhythmic central commands (neural BOLD) in the frequency band 0.1-0.14 Hz.

neuroscience↗