The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction.Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm).These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.

Compression optical coherence elastography (OCE) has shown promise in detecting diseases, such as breast cancer, based on changes in the elasticity of tissue. While the mechanical models used in OCE assume a flat surface, tissue typically exhibits surface topography that can lead to inaccurate estimation of elasticity in OCE images (elastograms). The coupling of surface topography and heterogeneous mechanical properties in tissue make it challenging to study the relative impact of surface roughness on image formation. To address this, we developed mechanically homogeneous phantoms that accurately replicate the surface topography of human breast tissue. Surface topography of breast tissue specimens was captured in three-dimensional (3-D) optical coherence tomography (OCT) scans. Molds replicating the surface roughness of tissue were generated using 3-D modelling and 3-D printing. The phantoms were then fabricated in the molds using polydimethylsiloxane. OCT was used to validate the accuracy of the phantom surface topography and the phantoms were then used to determine the impact of surface roughness in compression OCE elastograms. Surface roughness phantoms were shown to accurately reflect the surface topography of six breast tissue specimens with a correlation of 0.96 +/- 0.03. When imaged with a variant of compression OCE called quantitative micro-elastography, surface roughness resulted in a slight decrease in elasticity accuracy with a mean percentage error of 8.2 % for a flat phantom compared to 11.7 % for the roughness phantom, and a larger decrease in elasticity precision, or sensitivity, with a mean relative standard deviation of 9.4 % for the flat phantom compared to 21.2 %, for the roughness phantom. Our results show that contrast in elastograms moderately correlated with the phantom surface profile (r = 0.59, p < 0.001) and that surface roughness introduces spatially-varying elasticity that should be considered in the analysis of elastograms in compression OCE.

Core temperature (TC) changes, alongside exercise, affect hemodynamic responses across different conduit and microvascular beds. This study investigated impacts of ecologically valid environmental heat and exercise exposures on cerebral, skin and retinal vascular responses by combining physiological assessments alongside computational fluid dynamics (CFD) modeling. Young, healthy participants (n = 12) were exposed to environmental passive heating (PH), and heated exercise (HE) (ergometer cycling), in climate-controlled conditions (50 mins, 40°C, 50% relative humidity) while maintaining upright posture. Blood flow responses in the common carotid (CCA), internal carotid (ICA) and central retinal (CRA) arteries were assessed using Duplex ultrasound, while forearm skin microvascular blood flow responses were measured using optical coherence tomography angiography. Three-dimensional retinal hemodynamics (flow and pressure) were calculated via CFD simulation, enabling assessment of wall shear stress (WSS). TC rose following PH (+0.2°C, p = 0.004) and HE (+1.4°C, p < 0.001). PH increased skin microvascular blood flow (p < 0.001), whereas microvascular CRA flow decreased (p = 0.038), despite unchanged ICA flow. HE exacerbated these differences, with increased CCA flow (p = 0.007), unchanging ICA flow and decreased CRA flow (p < 0.001), and interactions between vascular (CCA vs. ICA p = 0.018; CCA vs. CRA p = 0.004) and microvascular (skin vs. retinal arteriolar p < 0.001) territories. Simulations revealed patterns of WSS and lumen pressure that uniformly decreased following HE. Under ecologically valid thermal challenge, different responses occur in distinct conduit and microvascular territories, with blood flow distribution favoring systemic thermoregulation, while flow may redistribute within the brain.

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.

Pancreaticoduodenal artery aneurysms have been associated with coeliac artery stenosis or occlusion. These aneurysms are rare, and their size may not be predictive of rupture risk. Wall shear stress has a potential role in the initiation, development and rupture of aneurysms. We investigated the influence of coeliac artery stenosis on wall shear stress in developing PDA aneurysm and in both ruptured and intact aneurysms to determine if ruptured aneurysms experience low WSS compared to intact cases. Computed tomography imaging was retrospectively collected and reconstructed into three-dimensional geometries with which blood flow simulations were performed to compare aneurysm wall shear stress between ruptured vs intact groups. Aneurysm initiation was investigated by digitally augmenting a case to represent a healthy geometry, with incremental coeliac artery stenosis then virtually applied. Coeliac artery stenosis resulted in gastroduodenal artery flow reversal and increased wall shear stress in the inferior pancreaticoduodenal arteries, where wall shear stress reached reaching 7.55 Pa at 80% stenosis. Wall shear stress was lower in ruptured aneurysms compared to intact cases (0.23(0.25) Pa vs. 0.37(0.26) Pa). Aneurysm WSS was not correlated to diameter (rs = 0.196, p = .564). Our results suggest 70% to 80% CA stenosis as a threshold for flow reversal through the inferior PDA and GDA, with corresponding high levels of WSS in the IPDA which may be responsible for the aneurysm initiation.

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.

The placenta is a temporary and complex organ critical for fetal development through its subtle but convoluted harmonization of endocrine, vascular, haemodynamic and exchange adaptations. Yet, due to experimental, technological and ethical constraints, this unique organ remains poorly understood. In silico tools are emerging as a powerful means to overcome these challenges and have the potential to actualize novel breakthroughs. Here, we present an interdisciplinary framework combining in vitro experiments used to develop an elegant and scalable in silico model of oxygen diffusion. We then use in utero imaging of placental perfusion and oxygenation in both control and growth-restricted rodent placentas for validation of our in silico model. Our framework revealed the structure-function relationship in the feto-placental vasculature; oxygen diffusion is impaired in growth-restricted placentas, due to the diminished arborization of growth-restricted feto-placental vasculature and the lack of decelerated flow for adequate oxygen diffusion and exchange. We highlight the mechanisms of impairment in a rat model of growth restriction, underpinned by placental vascular impairment. Our framework reports and validates the prediction of blood flow deceleration impairment in growth restricted placentas with the placenta’s oxygen transfer capability being significantly impaired, both globally and locally.### Competing Interest StatementThe authors have declared no competing interest.

A bstract The placenta is a temporary and complex organ critical for fetal development through its subtle but convoluted harmonization of endocrine, vascular, haemodynamic and exchange adaptations. Yet, due to experimental, technological and ethical constraints, this unique organ remains poorly understood. In silico tools are emerging as a powerful means to overcome these challenges and have the potential to actualize novel breakthroughs. Here, we present an interdisciplinary framework combining in vitro experiments used to develop an elegant and scalable in silico model of oxygen diffusion. We then use in utero imaging of placental perfusion and oxygenation in both control and growth-restricted rodent placentas for validation of our in silico model. Our framework revealed the structure-function relationship in the feto-placental vasculature; oxygen diffusion is impaired in growth-restricted placentas, due to the diminished arborization of growth-restricted feto-placental vasculature and the lack of decelerated flow for adequate oxygen diffusion and exchange. We highlight the mechanisms of impairment in a rat model of growth restriction, underpinned by placental vascular impairment. Our framework reports and validates the prediction of blood flow deceleration impairment in growth restricted placentas with the placenta’s oxygen transfer capability being significantly impaired, both globally and locally.

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.

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, Gαo) 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-Gαo 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.