Modelling large scale artery haemodynamics from the heart to the eye in response to simulated microgravity.

We investigated variations in haemodynamics in response to simulated microgravity across a semi-subject-specific three-dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth gravity case and a simulated microgravity case. Under simulated microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates that 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data-specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to simulated microgravity, relative to an upright position in Earth gravity.

Comparison of computational fluid dynamics with transcranial Doppler ultrasound in response to physiological stimuli.

Cerebrovascular haemodynamics are sensitive to multiple physiological stimuli that require synergistic response to maintain adequate perfusion. Understanding haemodynamic changes within cerebral arteries is important to inform how the brain regulates perfusion; however, methods for direct measurement of cerebral haemodynamics in these environments are challenging. The aim of this study was to assess velocity waveform metrics obtained using transcranial Doppler (TCD) with flow-conserving subject-specific three-dimensional (3D) simulations using computational fluid dynamics (CFD). Twelve healthy participants underwent head and neck imaging with 3 T magnetic resonance angiography. Velocity waveforms in the middle cerebral artery were measured with TCD ultrasound, while diameter and velocity were measured using duplex ultrasound in the internal carotid and vertebral arteries to calculate incoming cerebral flow at rest, during hypercapnia and exercise. CFD simulations were developed for each condition, with velocity waveform metrics extracted in the same insonation region as TCD. Exposure to stimuli induced significant changes in cardiorespiratory measures across all participants. Measured absolute TCD velocities were significantly higher than those calculated from CFD (P range < 0.001-0.004), and these data were not correlated across conditions (r range 0.030-0.377, P range 0.227-0.925). However, relative changes in systolic and time-averaged velocity from resting levels exhibited significant positive correlations when the distinct techniques were compared (r range 0.577-0.770, P range 0.003-0.049). Our data indicate that while absolute measures of cerebral velocity differ between TCD and 3D CFD simulation, physiological changes from resting levels in systolic and time-averaged velocity are significantly correlated between techniques.

Multimodal Imaging and Analysis of the Neuroanatomical Organization of the Primary Olfactory Inputs in the Brownbanded Bamboo Shark, Chiloscyllium punctatum.

There is currently a limited understanding of the morphological and functional organization of the olfactory system in cartilaginous fishes, particularly when compared to bony fishes and terrestrial vertebrates. In this fish group, there is a clear paucity of information on the characterization, density, and distribution of olfactory receptor neurons (ORNs) within the sensory olfactory epithelium lining the paired olfactory rosettes, and their functional implications with respect to the hydrodynamics of incurrent water flow into the nares. This imaging study examines the brownbanded bamboo shark Chiloscyllium punctatum (Elasmobranchii) and combines immunohistochemical labeling using antisera raised against five G-protein α-subunits (Gαs/olf, Gαq/ 11 / 14, Gαi- 1 / 2 / 3, Gαi- 3, Gα o ) with light and electron microscopy, to characterize the morphological ORN types present. Three main ORNs ("long", "microvillous" and "crypt-like") are confirmed and up to three additional microvilli-bearing types are also described; "Kappe-like" (potential or homologous "Kappe" as in teleosts), "pear-shaped" and "teardrop-shaped" cells. These morphotypes will need to be confirmed molecularly in the future. Using X-ray diffusible iodine-based contrast-enhanced computed tomography (diceCT), high-resolution scans of the olfactory rosettes, olfactory bulbs (OBs), peduncles, and telencephalon reveal a lateral segregation of primary olfactory inputs within the OBs, with distinct medial and lateral clusters of glomeruli, suggesting a potential somatotopic organization. However, most ORN morphotypes are found to be ubiquitously distributed within the medial and lateral regions of the olfactory rosette, with at least three microvilli-bearing ORNs labeled with anti-Gα o found in significantly higher densities in lateral lamellae [in lateral lamellae] and on the anterior portion of lamellae (facing the olfactory cavity). These microvilli-bearing ORN morphotypes (microvillous, "Kappe-like," "pear-shaped," and "teardrop-shaped") are the most abundant across the olfactory rosette of this species, while ciliated ORNs are less common and crypt cells are rare. Spatial simulations of the fluid dynamics of the incurrent water flow into the nares and within the olfactory cavities indicate that the high densities of microvilli-bearing ORNs located within the lateral region of the rosette are important for sampling incoming odorants during swimming and may determine subsequent tracking behavior.

Assessment of cerebrovascular responses to physiological stimuli in identical twins using multimodal imaging and computational fluid dynamics.

There is acknowledged variability in the Circle of Willis (CoW) in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. We aimed to demonstrate the feasibility of combining high-resolution imaging techniques and computational fluid dynamics (CFD) to describe cerebrovascular structure and function in vivo. We tested our methodology by examining the null hypothesis that monozygotic twins (18-30 yr) would exhibit similar CoW structure and function. Six twin pairs underwent 3T magnetic resonance angiography of the head and neck and B-mode Doppler ultrasound for velocity and diameter recordings in the vertebral and internal carotid arteries under three conditions (rest, hypercapnia, and exercise). Artery diameter, length, tortuosity, and bifurcation angle were assessed in regions of interest of the CoW. We simulated hemodynamics to determine the cardiac-cycle time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). We observed low and insignificant intraclass correlations (ICC) between twins in all regions for diameter (ICC range 0.000-0.657, P > 0.05), two of four regions for length (ICC range 0.355-0.368, P > 0.05), all regions for tortuosity (ICC range 0.270-0.505, P > 0.05), and all bifurcation angles (ICC range 0.000-0.547, P > 0.05). Similarly, no significant correlations were apparent for cerebral blood flow or CFD-derived measures of TAWSS, OSI, and RRT, at rest or in response to hypercapnia or exercise. Therefore, differences exist in CoW structure and associated shear stress in response to physiological stimulation. These data suggest that the structure, function, and health of cerebrovascular arteries are not primarily genetically dependent.NEW & NOTEWORTHY There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. Using a combination of magnetic resonance imaging, high-resolution Doppler ultrasound, and computational fluid dynamic modeling, we show that monozygotic twins exhibit differences in cerebrovascular structure and function when exposed to physiological stimuli. These data suggest that the morphology, function, and health of cerebrovascular arteries are not primarily genetically determined.