Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy

Review of photoacoustic imaging plus X

Photoacoustic imaging (PAI) is a novel modality in biomedical imaging technology that combines the rich optical contrast with the deep penetration of ultrasound. To date, PAI technology has found applications in various biomedical fields. In this review, we present an overview of the emerging research frontiers on PAI plus other advanced technologies, named as PAI plus X, which includes but not limited to PAI plus treatment, PAI plus new circuits design, PAI plus accurate positioning system, PAI plus fast scanning systems, PAI plus novel ultrasound sensors, PAI plus advanced laser sources, PAI plus deep learning, and PAI plus other imaging modalities. We will discuss each technology's current state, technical advantages, and prospects for application, reported mostly in recent three years. Lastly, we discuss and summarize the challenges and potential future work in PAI plus X area

A Review of the Circle of Willis: Investigative Methods, Anatomical Variations and Correlated Ischemic Brain Diseases

The Circle of Willis (CoW) is the most important collateral pathway communicating between the bilateral carotid system and the posterior circulation. Many techniques have been used to investigate the configuration and function of the CoW and their advantages and disadvantages are reviewed here. In previous studies, morphometric variation in CoW has been widely detected; however, the frequency of variation ranges largely, between 10% and 85%. Some differences in reported frequency may reflect differences in: the definition of CoW variation, the methods used to examine variation and study populations. Two conclusions, however, are clear: (i) the prevalence of variation in the posterior circle is higher than in that of the anterior circle; and (ii) variations in the CoW are correlated with cerebral or carotid vessel diseases. Although the cause of the variants remains unclear, both genetic background and hemodynamics could play important roles. Lastly, the correlation between the CoW and ischemic brain diseases is discussed. In future, artificial intelligence will be helpful for evaluating the CoW

Accurate geometry reconstruction of vascular structures using implicit splines

3-D visualization of blood vessel from standard medical datasets (e.g. CT or MRI) play an important role in many clinical situations, including the diagnosis of vessel stenosis, virtual angioscopy, vascular surgery planning and computer aided vascular surgery. However, unlike other human organs, the vasculature system is a very complex network of vessel, which makes it a very challenging task to perform its 3-D visualization. Conventional techniques of medical volume data visualization are in general not well-suited for the above-mentioned tasks. This problem can be solved by reconstructing vascular geometry. Although various methods have been proposed for reconstructing vascular structures, most of these approaches are model-based, and are usually too ideal to correctly represent the actual variation presented by the cross-sections of a vascular structure. In addition, the underlying shape is usually expressed as polygonal meshes or in parametric forms, which is very inconvenient for implementing ramification of branching. As a result, the reconstructed geometries are not suitable for computer aided diagnosis and computer guided minimally invasive vascular surgery. In this research, we develop a set of techniques associated with the geometry reconstruction of vasculatures, including segmentation, modelling, reconstruction, exploration and rendering of vascular structures. The reconstructed geometry can not only help to greatly enhance the visual quality of 3-D vascular structures, but also provide an actual geometric representation of vasculatures, which can provide various benefits. The key findings of this research are as follows: 1. A localized hybrid level-set method of segmentation has been developed to extract the vascular structures from 3-D medical datasets. 2. A skeleton-based implicit modelling technique has been proposed and applied to the reconstruction of vasculatures, which can achieve an accurate geometric reconstruction of the vascular structures as implicit surfaces in an analytical form. 3. An accelerating technique using modern GPU (Graphics Processing Unit) is devised and applied to rendering the implicitly represented vasculatures. 4. The implicitly modelled vasculature is investigated for the application of virtual angioscopy

Zebrafish models of cerebrovascular disease

Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish (Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens

Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System

The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. However, the presence of advection in neuropil is contested and solutes are claimed to be transported by diffusion only. To address this controversy, we implemented a regularized version of the optimal mass transport (rOMT) problem, wherein the advection/diffusion equation is the only a priori assumption required. rOMT analysis with a Lagrangian perspective of GS transport revealed that solute speed was faster in CSF compared to grey and white matter. Further, rOMT analysis also demonstrated 2-fold differences in regional solute speed within the brain. Collectively, these results imply that advective transport dominates in CSF while diffusion and advection both contribute to GS transport in parenchyma. In a rat model of cerebral small vessel disease (cSVD), solute transport in the perivascular spaces (PVS) and PVS-to-tissue transfer was slower compared to normal rats. Thus, the analytical framework of rOMT provides novel insights in the local dynamics of GS transport that may have implications for neurodegenerative diseases. Future studies should apply the rOMT analysis approach to confirm GS transport reductions in humans with cSVD