Impaired cerebrospinal fluid transport due to idiopathic subdural hematoma in pig: an unusual case

Background We report the effects of the presentation of an idiopathic subdural hematoma (SDH) in an adult domestic pig on the glymphatic system, a brain-wide solute clearance system. This accidental finding is based on our recently published study that described this system for the first time in large mammals. Our current results define the need to investigate cerebrovascular pathologies that could compromise glymphatic function in gyrencephalic animal models as a tool to bridge rodent and human glymphatic studies. Case presentation The pig underwent intracisternal infusion of a fluorescent tracer under general anesthesia to delineate cerebrospinal fluid (CSF) pathways, and was euthanized at the end of 3 h of tracer circulation. During brain isolation, a hematoma measuring approximately 15 × 35 mm in size beneath the dura was evident overlying fronto-parietal brain surface. Interestingly, CSF tracer distribution was markedly reduced on dorsal, lateral and ventral surfaces of the brain when compared with a control pig that was infused with the same tracer. Furthermore, regional distribution of tracer along the interhemispheric fissure, lateral fissure and hippocampus was 4–5-fold reduced in comparison with a control pig. Microscopically, glial-fibrillary acidic protein and aquaporin-4 water channel immunoreactivities were altered in the SDH pig brain. Conclusions This is the first case of impaired glymphatic pathway due to an idiopathic SDH in a pig. Potential etiology could involve an acceleration-deceleration injury inflicted prior to arrival at our housing facility (e.g., during animal transportation) leading to disruption of bridging veins along the superior sagittal sinus and impairing CSF pathways in the whole brain. This accidental finding of globally impaired glymphatic function sheds light on a novel consequence of SDH, which may play a role in the enhanced cognitive decline seen in elderly presenting with chronic SDH.

Predicting Groundwater Flow and Solute Transport in the Heterogeneous Aquifer Sandbox Using Different Parameter Estimation Methods

<p>Protection and management of groundwater resources demand high-resolution distributions of hydraulic parameters (e.g., hydraulic conductivity (K) and specific storage (Ss)) of aquifers. In the past, these parameters were obtained by traditional analytical solutions (e.g., Theis (1935) or Cooper and Jacob (1946)). However, traditional methods assume the aquifer to be homogeneous and yield the equivalent parameter, which are averages over a large volume and are insufficient for predicting groundwater flow and solute transport process (Butler & Liu, 1993). For obtaining the aquifer heterogeneity, some scholars have used kriging (e.g., Illman et al., 2010) and hydraulic tomography (HT) (e.g., Yeh & Liu, 2000; Zhu & Yeh, 2005) to describe the K distribution.</p><p>In this study, the laboratory heterogeneous aquifer sandbox is used to investigate the effect of different hydraulic parameter estimation methods on predicting groundwater flow and solute transport process. Conventional equivalent homogeneous model, kriging and HT are used to characterize the heterogeneity of sandbox aquifer. A number of the steady-state head data are collected from a series of single-hole pumping tests in the lab sandbox, and are then used to estimate the K fields of the sandbox aquifer by the steady-state inverse modeling in HT survey which was conducted using the SimSLE algorithm (Simultaneous SLE, Xiang et al., 2009), a built-in function of the software package of VSAFT2. The 40 K core samples from the sandbox aquifer are collected by the Darcy experiments, and are then used to obtain K fields through kriging which was conducted using the software package of Surfer 13. The role of prior information on improving HT survey is then discussed. The K estimates by different methods are used to predict the process of steady-state groundwater flow and solute transport, and evaluate the merits and demerits of different methods, investigate the effect of aquifer heterogeneity on groundwater flow and solute transport.</p><p>According to lab sandbox experiments results, we concluded that compared with kriging, HT can get higher precision to characterize the aquifer heterogeneity and predict the process of groundwater flow and solute transport. The 40 K fields from the K core samples are used as priori information of HT survey can promote the accuracy of K estimates. The conventional equivalent homogeneous model cannot accurately predict the process of groundwater flow and solute transport in heterogeneous aquifer. The enhancement of aquifer heterogeneity will lead to the enhancement of the spatial variability of tracer distribution and migration path, and the dominant channel directly determines the migration path and tracer distribution.</p>

Glymphatic pathways in the gyrencephalic brain

Identification of the perivascular compartment as the point of exchange between cerebrospinal fluid (CSF) and interstitial fluid mediating solute clearance in the brain, named the glymphatic system, has emerged as an important clearance pathway for neurotoxic peptides such as amyloid-beta. However, the foundational science of the glymphatic system is based on rodent studies. Here we investigated whether the glymphatic system exists in a large mammal with a highly gyrified brain. CSF penetration into the brain via perivascular pathways, a hallmark of glymphatic function, was seen throughout the gyrencephalic cortex and subcortical structures, validating the conservation of the glymphatic system in a large mammal. Macroscopic CSF tracer distribution followed the sulci and fissures showing that these folds enhance CSF dispersion. Three-dimensional renditions from light sheet microscopy showed a PVS influx density 4-fold larger in the pig brain than in mice. This demonstrates the existence of an advanced solute transport system in the gyrencephalic brain that could be utilised therapeutically for enhancing waste clearance.

Magnetic particle imaging of particle dynamics in complex matrix systems

Magnetic particle imaging (MPI) is a young imaging modality for biomedical applications. It uses magnetic nanoparticles as a tracer material to produce three-dimensional images of the spatial tracer distribution in the field-of-view. Since the tracer magnetization dynamics are tied to the hydrodynamic mobility via the Brownian relaxation mechanism, MPI is also capable of mapping the local environment during the imaging process. Since the influence of viscosity or temperature on the harmonic spectrum is very complicated, we used magnetic particle spectroscopy (MPS) as an integral measurement technique to investigate the relationships. We studied MPS spectra as function of both viscosity and temperature on model particle systems. With multispectral MPS, we also developed an empirical tool for treating more complex scenarios via a calibration approach. We demonstrate that MPS/MPI are powerful methods for studying particle-matrix interactions in complex media.

An easy and low-cost biomagnetic methodology to study regional gastrointestinal transit in rats

The identification of gastrointestinal (GI) motility disorders requires the evaluation of regional GI transit, and the development of alternative methodologies in animals has a significant impact on translational approaches. Therefore, the purpose of this study was to validate an easy and low-cost methodology (alternate current biosusceptometry – ACB) for the assessment of regional GI transit in rats through images. Rats were fed a test meal containing magnetic tracer and phenol red, and GI segments (stomach, proximal, medial and distal small intestine, and cecum) were collected to assess tracer’s retention at distinct times after ingestion (0, 60, 120, 240, and 360 min). Images were obtained by scanning the segments, and phenol red concentration was determined by the sample’s absorbance. The temporal retention profile, geometric center, gastric emptying, and cecum arrival were evaluated. The correlation coefficient between methods was 0.802, and the temporal retention of each segment was successfully assessed. GI parameters yielded comparable results between methods, and ACB images presented advantages as the possibility to visualize intrasegmental tracer distribution and the automated scan of the segments. The imaging approach provided a reliable assessment of several parameters simultaneously and may serve as an accurate and sensitive approach for regional GI research in rats.

Object surface reconstruction from flow tracers

A method to identify the surface of solid models immersed in fluid flows is devised that examines the spatial distribution of flow tracers. The fluid–solid interface is associated with the distance from the center of a circle to the centroid of the tracers ensemble captured within it. The theoretical foundation of the method is presented for 2D planar interfaces in the limit of a continuous tracer distribution. The discrete regime is analyzed, yielding the uncertainty of this estimator. Also the errors resulting from curved interfaces are discussed. The method's working principle is illustrated using synthetic data of a 2D cambered airfoil, showing that one of the limitations is the treatment of an object thinner than the search circle diameter. The method is readily adapted to 3D and applied to the 3D PTV data of the flow around a juncture. The surface is reconstructed within the expected uncertainty, and specific limitations, such as the smoothing of sharp edges is observed. Graphic abstract

Comparative application and optimization of different single-borehole dilution test techniques

Single-borehole dilution tests (SBDTs) are a method for characterizing groundwater monitoring wells and boreholes, and are based on the injection of a tracer into the saturated zone and the observation of concentration over depth and time. SBDTs are applicable in all aquifer types, but especially interesting in heterogeneous karst or fractured aquifers. Uniform injections aim at a homogeneous tracer concentration throughout the entire saturated length and provide information about inflow and outflow horizons. Also, in the absence of vertical flow, horizontal filtration velocities can be calculated. The most common method for uniform injections uses a hosepipe to inject the tracer. This report introduces a simplified method that uses a permeable injection bag (PIB) to achieve a close-to-uniform tracer distribution within the saturated zone. To evaluate the new method and to identify advantages and disadvantages, several tests have been carried out, in the laboratory and in multiple groundwater monitoring wells in the field. Reproducibility of the PIB method was assessed through repeated tests, on the basis of the temporal development of salt amount and calculated apparent filtration velocities. Apparent filtration velocities were calculated using linear regression as well as by inverting the one-dimensional (1D) advection-dispersion equation using CXTFIT. The results show that uniform-injection SBDTs with the PIB method produce valuable and reproducible outcomes and contribute to the understanding of groundwater monitoring wells and the respective aquifer. Also, compared to the hosepipe method, the new injection method requires less equipment and less effort, and is especially useful for deep boreholes.

Glymphatic function in the gyrencephalic brain

ABSTRACTIdentification of the perivascular compartment as the point of exchange between cerebrospinal fluid (CSF) and interstitial fluid mediating solute clearance in the brain, named the glymphatic system, has emerged as an important clearance pathway for neurotoxic peptides such as amyloid-beta. However, the foundational science of the glymphatic system is based on rodent studies. Here we investigated whether the glymphatic system exists in a large mammal with a highly gyrified brain. CSF penetration into the brain via perivascular pathways, a hallmark of glymphatic function, was seen throughout the gyrencephalic cortex and subcortical structures, validating the conservation of the glymphatic system in a large mammal. Macroscopic CSF tracer distribution followed the sulci and fissures showing that the gyri enhance CSF dispersion. Three-dimensional renditions from light sheet microscopy showed that CSF influx through perivascular spaces was 4-fold more extensive in the pig brain than in mice. This demonstrates the existence of an advanced solute transport system in the gyrencephalic brain that could be utilised therapeutically for enhancing waste clearance.