Biology subjects

Kruizinga, P.

Publications and source records attributed to Kruizinga, P..

5 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

LABEL-FREE HEMODYNAMIC MAPPING VIA ULTRAFAST POWER DOPPLER-ENHANCED PHOTOACOUSTIC IMAGING REVEALS EARLY THERAPY-INDUCED FUNCTIONAL CHANGES IN THE TUMOR.

Real-time, non-invasive imaging of tumor vascular function is critical for assessing treatment response and informing therapeutic decisions. In this study, we present a dual-modality imaging approach that integrates Ultrafast power Doppler ultrasound (UPD) with multispectral photoacoustic (PA) imaging to quantify spatiotemporal changes in tumor oxygenation and perfusion following photodynamic therapy (PDT). Our results demonstrate that PDT induces dose- and time-dependent spatial heterogenic alterations in both oxygenation and perfusion. To better interpret the spatial interplay between tumor oxygenation and vascular perfusion, we developed a Vascular Function Index (VFI), which classifies tumor subregions into four functional quadrants based on perfusion and oxygenation status at every voxel within the 3D tumor region. This framework revealed dynamic, time-dependent changes in tumor hypoxia and perfusion, with high-dose treatment groups showing a progressive increase in hypoxic and non-perfused regions, underscoring the spatiotemporal nature of PDT-induced vascular response. TeaserTumoral Blood flow and oxygenation interplay, assessed by label-free imaging, unravels heterogeneous therapy response.

biophysics↗

bioRxiv2024

Mobile Human Brain Imaging using Functional Ultrasound

Imagine being able to study the human brain in real-world scenarios while the subject displays natural behaviors such as locomotion, social interaction, or spatial navigation. The advent of ultrafast ultrasound imaging brings us closer to this goal with functional Ultrasound imaging (fUSi), a new mobile neuroimaging technique. Here, we present real-time fUSi monitoring of brain activity during walking in a subject with a clinically approved sonolucent skull implant. Our approach utilizes personalized 3D-printed fUSi-helmets for stability, optical tracking for cross-modal validation with fMRI, advanced signal processing to estimate hemodynamic responses and facial tracking of a lick licking paradigm. These combined efforts allowed us to show consistent fUSi signals over 20 months, even during high-motion activities like walking. These results demonstrate the feasibility of fUSi for monitoring brain activity in real-world contexts, marking an important milestone for fUSi-based insights in clinical and neuroscientific research.

neuroscience↗

bioRxiv2023

Vascular abnormalities in heart and brain are associated with cardiovascular and neurological symptoms in a novel mouse model for Williams syndrome

Williams syndrome is a developmental disorder caused by a microdeletion entailing the loss of a single copy of 25-27 genes on chromosome 7q11.23. Patients suffer from cardiovascular and neuropsychological symptoms. Structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the hemizygous loss of the elastin (ELN) gene. In contrast, the neuropsychological consequences of Williams syndrome, including sensorimotor deficits, hypersociability and cognitive impairments, have been mainly attributed to altered expression of transcription factors like LIMK1, GTF2I and GTF2IRD1, while the potential impact of altered cerebrovascular function has been largely overlooked. To study the relationship between Williams syndrome mutations and vascularization of both the heart and brain, we generated a mouse model carrying a relatively long microdeletion (LD) that includes the Ncf1 gene, thereby minimizing the confounding impact of hypertension. LD mice had elongated and tortuous aortas but, unlike Eln haploinsufficient mice, showed no signs of structural cardiac hypertrophy. Remarkably, LD mice also displayed structural abnormalities in coronary and brain vessels, including disorganized extracellular matrices. Importantly, LD mice faithfully replicated both cardiovascular and neuropsychological symptoms observed in patients. The phenotype was even more comprehensive than former models, with structure-function correlations evident in aberrant auditory and motor behaviors resembling those in patients with Williams syndrome. Together, our findings suggest that not only cardiovascular but also neuropsychological symptoms in Williams syndrome may be driven in part by vascular abnormalities affecting both heart and brain. Significance StatementWilliams syndrome is caused by microdeletion of 25-27 genes on chromosome 7q11.23, resulting in cardiovascular and neuropsychological symptoms. It remains unclear how the affected genes interact and whether cardiovascular deficits influence brain function. We developed and characterized a mouse model with the longest Williams syndrome microdeletion to date. This model reveals interactions between genes that can be compensatory or additive: haploinsufficiency of Ncf1 may counteract the cardiac hypertrophy caused by Eln deletion, while vascular defects that are potentially due to Eln haploinsufficiency extend to the brain and may worsen neuropsychological symptoms. Our findings support the hypothesis that structural vascular deficits putatively contribute to both cardiac and cognitive phenotypes in Williams syndrome, opening new avenues for understanding and treating this syndrome.

systems biology↗

bioRxiv2018

3D Functional Ultrasound Imaging of Pigeons

Recent advances in ultrasound Doppler imaging have allowed to visualize brain activity in small mammalian species such as rats and mice. In birds, this type of functional ultrasound imaging was impossible up to now because birds have physiological characteristics that are unfavorable for current functional ultrasound acquisition schemes. Here, we introduce a high-definition functional ultrasound acquisition method (HDfUS) acquiring 20,000 frames per second continuously. This enabled first successful functional studies on awake pigeons subjected to auditory and visual stimulation. We show that the improved spatiotemporal resolution and sensitivity of HDfUS allows to visualize and investigate the temporally resolved 3D neural activity evoked by a complex stimulation pattern, such as a moving light source. This illustrates the enormous potential of HDfUS imaging to become a new standard functional brain imaging method revealing unknown, stimulus related hemodynamics at excellent signal-to-noise ratio and spatiotemporal resolution.

neuroscience↗