Background: Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models. Methods: We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters. Results: At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/ (mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route. Conclusions: The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

The central nervous system coordinates movement through forces generated by motor units (MUs) in skeletal muscles. To analyze MUs function is essential in sports, rehabilitation medicine applications, and neuromuscular diagnostics. The MUs and their function are studied using electromyography. Typically, these methods study only a small muscle volume (1 mm 3) or only a superficial (<1 cm) volume of the muscle. Here we introduce a method to identify so-called mechanical units, i.e., the mechanical response of electrically active MUs, in the whole muscle (4 × 4 cm, cross-sectional) under voluntary contractions by ultrafast ultrasound imaging and spatiotemporal decomposition. We evaluate the performance of the method by simulation of active MUs' mechanical response under weak contractions. We further test the experimental feasibility on eight healthy subjects. We show the existence of mechanical units that contribute to the tissue dynamics in the biceps brachii at low force levels and that these units are similar to MUs described by electromyography with respect to the number of units, territory sizes, and firing rates. This study introduces a new potential neuromuscular functional imaging method, which could be used to study a variety of questions on muscle physiology that previously were difficult or not possible to address.

According to some theories, obstruction of CSF flow produces a pressure drop in the subarachnoid space in accordance with the Bernoulli theorem that explains the development of syringomyelia below the obstruction. However, Bernoulli's principle applies to inviscid stationary flow unlike CSF flow. Therefore, we performed a series of computational experiments to investigate the relationship between pressure drop, flow velocities, and obstructions under physiologic conditions. We created geometric models with dimensions approximating the spinal subarachnoid space with varying degrees of obstruction. Pressures and velocities for constant and oscillatory flow of a viscid fluid were calculated with the Navier-Stokes equations. Pressure and velocity along the length of the models were also calculated by the Bernoulli equation and compared with the results from the Navier-Stokes equations. In the models, fluid velocities and pressure gradients were approximately inversely proportional to the percentage of the channel that remained open. Pressure gradients increased minimally with 35% obstruction and with factors 1.4, 2.2 and 5.0 respectively with 60, 75 and 85% obstruction. Bernoulli's law underestimated pressure changes by at least a factor 2 and predicted a pressure increase downstream of the obstruction, which does not occur. For oscillatory flow the phase difference between pressure maxima and velocity maxima changed with the degree of obstruction. Inertia and viscosity which are not factored into the Bernoulli equation affect CSF flow. Obstruction of CSF flow in the cervical spinal canal increases pressure gradients and velocities and decreases the phase lag between pressure and velocity.

An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.