Biology subjects

Ringstad, G.

Publications and source records attributed to Ringstad, G..

5 recordsLinked to original sources

bioRxiv2026

Low-rank tensor decompositions reveal coupled spatiotemporal patterns of CSF tracer transport in the human brain

Intrathecal contrast-enhanced longitudinal MRI, or glymphatic MRI (gMRI), provides a unique clinical window into human cerebrospinal fluid (CSF) transport, interstitial fluid (ISF) interaction, and the glymphatic system. However, standard analyses flatten these multi-subject longitudinal data into univariate comparisons across regions of interest, destroying the underlying multi-way structure and obscuring coupled spatiotemporal dynamics. Here we analyze gMRI data from 92 patients (43 diagnosed with idiopathic normal pressure hydrocephalus [iNPH] and 49 reference subjects [REF]) using unsupervised non-negative low-rank tensor decompositions that treat tracer signal in CSF and brain parenchyma simultaneously. The analysis is stratified by sex to avoid confounding diagnosis with the sex imbalance between cohorts. We recover four replicable components, three of which resolve distinct transport pathways capturing CSF--ISF interaction: distribution of tracer in the supratentorial subarachnoid space and cerebral gray and white matter at 24 hours; transient early influx in regions consistent with transport along major cerebral arteries; and tracer influx to ventricular CSF, also called ventricular reflux. The first two components are positively correlated and thus establish a direct quantitative link between early-stage influx and 24-hour tracer distribution. Moreover, the expression of the two influx pathways varies significantly between REF and iNPH cohorts, demonstrating how unsupervised tensor decompositions provide an automated, data-driven framework to stratify patient groups and derive quantitative markers of solute transport in the human brain.

neuroscience↗

bioRxiv2025

The impact of human brain geometry on the transport of an intrathecal tracer

BackgroundIntrathecal contrast-enhanced magnetic resonance imaging (MRI), utilizing the contrast agent gadobutrol as cerebrospinal fluid (CSF) tracer is emerging as a useful method to study glymphatic function in the human brain. A consistent finding with this technique is large inter-individual variability regarding tracer propagation. In this study, we outline an approach which predicts the distribution of tracer in the parenchyma based only on geometric information from brain tissue as captured by MRI, addressing one possible explanation for this variability. MethodsRegistrations are computed from pre-injection MRI, and used to map images at 24 hours after tracer injection to perform predictions of tracer enrichment in the parenchyma in other patients. We apply the method to a dataset of human brain MRI of 134 patients examined for different tentative diagnoses including idiopathic normal pressure hydrocephalus, spontaneous intracranial hypotension and idiopathic intracranial hypertension, as well as a group of reference patients. ResultsTracer enrichment mapped between patients by image registration correlate strongly with actual observed enrichment. For patients in the reference group, the relative root mean squared error on our predictions is on average 26% in the gray matter, and 15% or less in other brain regions. Predictions are generally less reliable in the gray matter, and for patients with identified CSF leaks. ConclusionWe show that predictions made from purely geometrical considerations correlate strongly with actual MRI tracer enrichment for patients with similar diagnoses, thus quantifying the role of geometry in tracer enrichment.

neuroscience↗

bioRxiv2025

Heterogeneity in human brain clearance adds resilience against tauopathy -- a computational model informed by glymphatic MRI

Neurotoxic protein fragments such as amyloid-beta and tau accumulate in characteristic staging patterns in Alzheimers disease (AD). The brain clears such metabolic substances via multiple different systems, including via the glymphatic (extracellular/extravascular) pathway. Here, we ask how the distinct features that characterize human glymphatic function would affect the prion-like cascade of protein invasion associated with AD. To address this question, we extract and analyze individual clearance rates from human glymphatic MRI (gMRI) data sets. These clearance rates define subject-specific maps of glymphatic clearance that vary both across cortical lobes and Braak staging regions. We apply these clearance maps as initial states in a computational network model linking misfolded proteins, tissue damage, and local clearance to simulate a series of individual proteinopathy trajectories. Our results show that the spatial heterogeneity in initial clearance induces characteristic propagation patterns, delaying and redirecting the disease progression. Moreover, reducing this spatial heterogeneity accelerates disease progression and induces staging patterns typically associated with AD. A comparison between well-rested subjects and subjects who underwent a single night of sleep deprivation did not reveal differences in initial clearance maps nor in simulated disease progression. These findings suggest that spatial heterogeneity in brain clearance may be a key factor for neurodegenerative resilience.

neuroscience↗

bioRxiv2023

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Whether you are reading, running or sleeping, your brain and its fluid environment continuously interacts to distribute nutrients and clear metabolic waste. Yet, the precise mechanisms for solute transport within the human brain have remained hard to quantify using imaging techniques alone. From multi-modal human brain MRI data sets in sleeping and sleep-deprived subjects, we identify and quantify CSF tracer transport parameters using forward and inverse subject-specific computational modelling. Our findings support the notion that extracellular diffusion alone is not sufficient as a brain-wide tracer transport mechanism. Instead, we show that human MRI observations align well with transport by either substantially enhanced (3.5x) extracellular diffusion in combination with local clearance rates corresponding to a tracer half-life of up to 5 hours, or by extracellular diffusion augmented by advection with brain-wide average flow speeds on the order of 1-9 {micro}m/min. Reduced advection fully explains reduced tracer clearance after sleep-deprivation, supporting the role of sleep and sleep deprivation on human brain clearance.

neuroscience↗

bioRxiv2022

CSF circulation and dispersion yield rapid clearancefrom intracranial compartments

In this paper we used a computational model to estimate the clearance of tracer driven by circulation of cere-brospinal fluid (CSF) produced in the choroid plexus (CP) located within the lateral ventricles. CSF was assumed to exit the subarachnoid space (SAS) via different outflow routes such as the parasagittal dura, cribriform plate and/or meningeal lymphatics. We also modelled a reverse case where fluid was produced within the spinal canal and absorbed in the CP in line with observation on certain iNPH patients. No directional interstitial fluid flow was assumed within the brain parenchyma. Tracers were injected into the foramen magnum. The models demonstrate that convection in the SAS yield rapid clearance from both the SAS and the brain interstitial fluid (ISF) and can speed up intracranial clearance from years, as would be the case for purely diffusive flow, to days.

neuroscience↗