Structure-function relationships in the feto-placental circulation from in silico interpretation of micro-CT vascular structures

A well-functioning placenta is critical for healthy fetal development, as the placenta brings fetal blood in close contact with nutrient rich maternal blood, enabling exchange of nutrients and waste between mother and fetus. The feto-placental circulation forms a complex branching structure, providing blood to fetal capillaries, which must receive sufficient blood flow to ensure effective exchange, but at a low enough pressure to prevent damage to placental circulatory structures. The branching structure of the feto-placental circulation is known to be altered in complications such as fetal growth restriction, and the presence of regions of vascular dysfunction (such as hypovascularity or thrombosis) are proposed to elevate risk of placental pathology. Here we present a methodology to combine micro-computed tomography and computational model-based analysis of the branching structure of the feto-placental circulation in ex vivo placentae from normal term pregnancies. We analyse how vascular structure relates to function in this key organ of pregnancy; demonstrating that there is a 'resilience' to placental vascular structure-function relationships. We find that placentae with variable chorionic vascular structures, both with and without a Hyrtl's anastomosis between the umbilical arteries, and those with multiple regions of poorly vascularised tissue are able to function with a normal vascular resistance. Our models also predict that by progressively introducing local heterogeneity in placental vascular structure, large increases in feto-placental vascular resistances are induced. This suggests that localised heterogeneities in placental structure could potentially provide an indicator of increased risk of placental dysfunction

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) of the orbit: a case report

© 2007 Fernandes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease

© 2018 American Physiological Society. All rights reserved. Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death and imposes major socioeconomic burdens globally. It is a progressive and disabling condition that severely impairs breathing and lung function. There is a lack of effective treatments for COPD, which is a direct consequence of the poor understanding of the underlying mechanisms involved in driving the pathogenesis of the disease. Toll-like receptor (TLR)2 and TLR4 are implicated in chronic respiratory diseases, including COPD, asthma and pulmonary fibrosis. However, their roles in the pathogenesis of COPD are controversial and conflicting evidence exists. In the current study, we investigated the role of TLR2 and TLR4 using a model of cigarette smoke (CS)-induced experimental COPD that recapitulates the hallmark features of human disease. TLR2, TLR4, and associated coreceptor mRNA expression was increased in the airways in both experimental and human COPD. Compared with wild-type (WT) mice, CS-induced pulmonary inflammation was unaltered in TLR2-deficient (Tlr2-/-) and TLR4-deficient (Tlr4-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2-/- mice but was attenuated in Tlr4-/- mice compared with CS-exposed WT controls. However, Tlr2-/- mice had increased CS-induced emphy-sema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD

Shape Analysis and Computational Fluid Simulations to Assess Feline Left Atrial Function and Thrombogenesis

In humans, there is a well-established relationship between atrial fibrillation (AF), blood flow abnormalities and thrombus formation, even if there is no clear consensus on the role of left atrial appendage (LAA) morphologies. Cats can also suffer heart diseases, often leading to an enlargement of the left atrium that promotes stagnant blood flow, activating the clotting process and promoting feline aortic thromboembolism. The majority of pathological feline hearts have echocardiographic evidence of abnormal left ventricular filling, usually assessed with 2D and Doppler echocardiography and standard imaging tools. Actually, veterinary professionals have limited access to advanced computational techniques that would enable a better understanding of feline heart pathologies with improved morphological and haemodynamic descriptors. In this work, we applied state-of-the-art image processing and computational fluid simulations based on micro-computed tomography images acquired in 24 cases, including normal cats and cats with varying severity of cardiomyopathy. The main goal of the study was to identify differences in the LA/LAA morphologies and blood flow patterns in the analysed cohorts with respect to thrombus formation and cardiac pathology. The obtained results show significant differences between normal and pathological feline hearts, as well as in thrombus vs non-thrombus cases and asymptomatic vs symptomatic cases, while it was not possible to discern in congestive heart failure with thrombus and from non-thrombus cases. Additionally, in-silico fluid simulations demonstrated lower LAA blood flow velocities and higher thrombotic risk in the thrombus cases

Photoacoustic imaging of the human placental vasculature

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin‐to‐twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry‐Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear‐array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS‐treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies

Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65998/1/jphysiol.2005.096073.pd

Quantifying the Link between Anatomical Connectivity, Gray Matter Volume and Regional Cerebral Blood Flow: An Integrative MRI Study

Background In the graph theoretical analysis of anatomical brain connectivity, the white matter connections between regions of the brain are identified and serve as basis for the assessment of regional connectivity profiles, for example, to locate the hubs of the brain. But regions of the brain can be characterised further with respect to their gray matter volume or resting state perfusion. Local anatomical connectivity, gray matter volume and perfusion are traits of each brain region that are likely to be interdependent, however, particular patterns of systematic covariation have not yet been identified. Methodology/Principal Findings We quantified the covariation of these traits by conducting an integrative MRI study on 23 subjects, utilising a combination of Diffusion Tensor Imaging, Arterial Spin Labeling and anatomical imaging. Based on our hypothesis that local connectivity, gray matter volume and perfusion are linked, we correlated these measures and particularly isolated the covariation of connectivity and perfusion by statistically controlling for gray matter volume. We found significant levels of covariation on the group- and regionwise level, particularly in regions of the Default Brain Mode Network. Conclusions/Significance Connectivity and perfusion are systematically linked throughout a number of brain regions, thus we discuss these results as a starting point for further research on the role of homology in the formation of functional connectivity networks and on how structure/function relationships can manifest in the form of such trait interdependency

Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: the role of somatosensory and salience networks.

Atypical anorexia nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis; however, they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on the previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients' bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behavior in atypical AN might help designing specific treatment strategies