Biology subjects

Nelissen, F.

Publications and source records attributed to Nelissen, F..

4 recordsLinked to original sources

bioRxiv2026

Modeling behavior to disentangle motion-related effects in functional ultrasound imaging in awake, head-fixed mice

Functional ultrasound imaging (fUSI) enables brain-wide mapping of hemodynamic activity in awake rodents, offering a powerful bridge between systems neuroscience in animals and human neuroimaging. However, extending fUSI beyond tightly controlled sensory paradigms to more naturalistic behaviors is limited by motion-related confounds arising from locomotion, physiological arousal, and movement-linked neural activity. Here, we introduce a behavior-informed modeling framework that explicitly incorporates continuous measurements of running speed and head motion into a general linear model to account for motion-related variance while preserving interpretable task-related signals. We validate this approach in two head-fixed paradigms with distinct motion profiles: a visual stimulation task with minimal stimulus-driven movement, and a noxious stimulation task in which locomotion and arousal are intrinsic to the behavioral response. In both cases, explicit behavioral modeling recovers neural response patterns that more closely resemble low-motion reference conditions than blind, model-free denoising approaches. Critically, during noxious stimulation, behavior-informed modeling preserves shock-intensity-dependent activity in the primary somatosensory cortex that is attenuated by global component removal. These findings demonstrate that explicit modeling of behavior enables reliable interpretation of brain-wide fUSI signals during naturalistic, high-motion conditions, opening the door to studying affective and cognitive processes that were previously difficult to access with functional ultrasound imaging.

neuroscience↗

bioRxiv2025

Selective-plane Functional Ultrasound Neuroimaging

Functional ultrasound (fUS) is a sensitive neuroimaging technique that uses high frame rate ultrasound to monitor brain hemo-dynamics as a proxy for neural activity. Recent studies have demonstrated its potential for brain-machine interfaces (BMIs) in both primates and humans. However, current 2D fUS approaches are limited to a single brain slice, restricting the ability to decode widespread neural activity. While 3D fUS could overcome this, it demands high data throughput, increased computation, and higher temperature increases due to the requirement of a higher number of transmitted waves. To address this, we present selective-plane fUS, a method that leverages the wide field of view of row-column addressed (RCA) transducer arrays to capture activity in targeted brain regions without moving the probe. By electronically selecting imaging planes, this approach achieves higher spatio-temporal resolution with lower data and pulse repetition rate compared to 3D fUS, while preserving sensitivity to neurovascular signals. Our pipeline begins with a 3D functional activation scan to guide plane selection, followed by high frame rate focused wave (FW) imaging in coronal or sagittal slices. This method offers robust detection of visually evoked responses in rodents and reduces signal variability compared to 3D fUS. By imaging only functional regions of interest, selective-plane fUS cuts computational load by an order of magnitude, enables continuous 1000 Hz recordings, and reduces functional signal variability fivefold. We envision that this method will allow tailored continuous functional imaging of widespread neuronal activity in the human brain in a BMI context.

neuroscience↗

bioRxiv2025

Adaptive transcranial ultrasound Doppler imaging of the brain

The development of fully noninvasive, transcranial functional ultrasound (fUS) would increase the translatability and clinical potential of this neuroimaging modality. Unfortunately, transcranial fUS is hindered by skull-induced aberrations which degrade power Doppler image quality and lower sensitivity. As a result, a majority of fUS imaging studies rely on craniotomies or acoustically transparent cranial windows. To advance fUS technology further, we present an adaptive aberration correction method based on ray-tracing through 4 tissue layers (transducer lens, gel & skin, bone and brain tissue). Our method segments these layers, and estimates ultrasound wave speeds in each layer iteratively. Once a velocity model of the imaging plane of interest is retrieved, ultrafast power Doppler imaging of the brain is performed using a ray-tracing beamformer that accounts for wave refraction. We tested our method in three adult rats, and estimated wave speeds for the skin/gel layer (1628 {+/-} 7 m/s), skull bone (3247 {+/-} 110 m/s), and brain tissue (1526 {+/-} 55 m/s). After aberration correction, we measured an average adult rat skull thickness of 388 {+/-} 41 m in agreement with anatomical records. The largest improvements in Doppler imaging quality were observed in cortical brain layers adjacent to the skull, specifically lateral spatial resolution was improved by 32%. Our method consistently outperformed Doppler imaging based on traditional delay-and-sum (DAS) beamforming, which assumes a uniform sound speed.

neuroscience↗

bioRxiv2024

Nonlinear sound-sheet microscopy: imaging opaque organs at the capillary and cellular scale

Light-sheet fluorescence microscopy has revolutionized biology by visualizing dynamic cellular processes in three dimensions. However, light scattering in thick tissue and photobleaching of fluorescent reporters limit this method to studying thin or translucent specimens. Here we show that non-diffractive ultrasonic beams used in conjunction with a cross-amplitude modulation sequence and nonlinear acoustic reporters enable fast and volumetric imaging of targeted biological functions. We report volumetric imaging of tumor gene expression at the cm3 scale using genetically encoded gas vesicles, and localization microscopy of currently uncharted cerebral capillary networks using intravascular microbubble contrast agents. Nonlinear sound-sheet microscopy provides a [~]64x acceleration in imaging speed, [~]35x increase in imaged volume and [~]4x increase in classical imaging resolution compared to the state-of-the-art in biomolecular ultrasound.

bioengineering↗