Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed

EJS-Based Laboratory for Learning the Function of the Cardiovascular System

One of the career areas included in the field of Biomedical Engineering is the application of engineering system analysis: physiological modelling, simulation and control. This paper describes a Virtual Laboratory for the analysis and the study of Human circulatory system. The Virtual Laboratory is based on the compilation of several mathematical models described in the literature. Presented application has been build using MATLAB/Simulink and EJS, so it combines good computation capabilities and it is completely interactive. The Virtual Laboratory is designed in order to understand the operation of the circulatory system under normal conditions, and to predict circulatory variables at different levels of stimuli and conditions.Postprint (published version

Atypical gaze-following behaviour in infants with congenital heart disease

BACKGROUND Neurodevelopmental impairments are the most prevalent non-cardiac long-term sequelae in children with complex congenital heart disease (CHD). Deficits include the social-emotional and social-cognitive domains. Little is known about the predecessors of social-cognitive development in infants with CHD during the first year of life. Gaze-following behaviour can be used to measure early social-cognitive abilities. AIMS To assess gaze-following development in infants with CHD compared to healthy controls. STUDY DESIGN Prospective cohort study. PARTICIPANTS Twenty-three infants who underwent neonatal correction for CHD and 84 healthy controls. OUTCOME MEASURES Gaze-following behaviour was assessed by eye tracking at 6 and 12 months. Difference scores for first fixation, fixation frequency and fixation duration towards the gaze-cued object were calculated across 6 trials and compared between groups at both testing time points while adjusting for known confounders. Linear mixed models were calculated to assess the longitudinal trajectory of gaze-following development while accounting for the nested and dependent data structure. RESULTS At 6 months, no difference in gaze-following behaviour between CHD and healthy controls was found. At 12 months, fixation frequency towards the gaze-cued was lower and looking duration was shorter in CHD compared to controls (p = 0.0077; p = 0.0068). Infants with CHD showed less increase with age in the fixation frequency towards the congruent object (p = 0.041) compared to controls. CONCLUSION During the first year of life, gaze-following development diverges in infants with CHD compared to healthy controls. Further research is needed to investigate the clinical relevance of these findings and the association with later social-cognitive development

Macaques preferentially attend to visual patterns with higher fractal dimension contours.

Animals' sensory systems evolved to efficiently process information from their environmental niches. Niches often include irregular shapes and rough textures (e.g., jagged terrain, canopy outlines) that must be navigated to find food, escape predators, and master other fitness-related challenges. For most primates, vision is the dominant sensory modality and thus, primates have evolved systems for processing complicated visual stimuli. One way to quantify information present in visual stimuli in natural scenes is evaluating their fractal dimension. We hypothesized that sensitivity to complicated geometric forms, indexed by fractal dimension, is an evolutionarily conserved capacity, and tested this capacity in rhesus macaques (Macaca mulatta). Monkeys viewed paired black and white images of simulated self-similar contours that systematically varied in fractal dimension while their attention to the stimuli was measured using noninvasive infrared eye tracking. They fixated more frequently on, dwelled for longer durations on, and had attentional biases towards images that contain boundary contours with higher fractal dimensions. This indicates that, like humans, they discriminate between visual stimuli on the basis of fractal dimension and may prefer viewing informationally rich visual stimuli. Our findings suggest that sensitivity to fractal dimension may be a wider ability of the vertebrate vision system

From Molecules to the Masses : Visual Exploration, Analysis, and Communication of Human Physiology

Det overordnede målet med denne avhandlingen er tverrfaglig anvendelse av medisinske illustrasjons- og visualiseringsteknikker for å utforske, analysere og formidle aspekter ved fysiologi til publikum med ulik faglig nivå og bakgrunn. Fysiologi beskriver de biologiske prosessene som skjer i levende vesener over tid. Vitenskapen om fysiologi er kompleks, men samtidig kritisk for vår forståelse av hvordan levende organismer fungerer. Fysiologi dekker en stor bredde romlig-temporale skalaer og fordrer behovet for å kombinere og bygge bro mellom basalfagene (biologi, fysikk og kjemi) og medisin. De senere årene har det vært en eksplosjon av nye, avanserte eksperimentelle metoder for å detektere og karakterisere fysiologiske data. Volumet og kompleksiteten til fysiologiske data krever effektive strategier for visualisering for å komplementere dagens standard analyser. Hvilke tilnærminger som benyttes i visualiseringen må nøye balanseres og tilpasses formålet med bruken av dataene, enten dette er for å utforske dataene, analysere disse eller kommunisere og presentere dem. Arbeidet i denne avhandlingen bidrar med ny kunnskap innen teori, empiri, anvendelse og reproduserbarhet av visualiseringsmetoder innen fysiologi. Først i avhandlingen er en rapport som oppsummerer og utforsker dagens kunnskap om muligheter og utfordringer for visualisering innen fysiologi. Motivasjonen for arbeidet er behovet forskere innen visualiseringsfeltet, og forskere i ulike anvendelsesområder, har for en sammensatt oversikt over flerskala visualiseringsoppgaver og teknikker. Ved å bruke søk over et stort spekter av metodiske tilnærminger, er dette den første rapporten i sitt slag som kartlegger visualiseringsmulighetene innen fysiologi. I rapporten er faglitteraturen oppsummert slik at det skal være enkelt å gjøre oppslag innen ulike tema i rom-og-tid-skalaen, samtidig som litteraturen er delt inn i de tre høynivå visualiseringsoppgavene data utforsking, analyse og kommunikasjon. Dette danner et enkelt grunnlag for å navigere i litteraturen i feltet og slik danner rapporten et godt grunnlag for diskusjon og forskningsmuligheter innen feltet visualisering og fysiologi. Basert på arbeidet med rapporten var det særlig to områder som det er ønskelig for oss å fortsette å utforske: (1) utforskende analyse av mangefasetterte fysiologidata for ekspertbrukere, og (2) kommunikasjon av data til både eksperter og ikke-eksperter. Arbeidet vårt av mangefasetterte fysiologidata er oppsummert i to studier i avhandlingen. Hver studie omhandler prosesser som foregår på forskjellige romlig-temporale skalaer og inneholder konkrete eksempler på anvendelse av metodene vurdert av eksperter i feltet. I den første av de to studiene undersøkes konsentrasjonen av molekylære substanser (metabolitter) ut fra data innsamlet med magnetisk resonansspektroskopi (MRS), en avansert biokjemisk teknikk som brukes til å identifisere metabolske forbindelser i levende vev. Selv om MRS kan ha svært høy sensitivitet og spesifisitet i medisinske anvendelser, er analyseresultatene fra denne modaliteten abstrakte og vanskelige å forstå også for medisinskfaglige eksperter i feltet. Vår designstudie som undersøkte oppgavene og kravene til ekspertutforskende analyse av disse dataene førte til utviklingen av SpectraMosaic. Dette er en ny applikasjon som gjør det mulig for domeneeksperter å analysere konsentrasjonen av metabolitter normalisert for en hel kohort, eller etter prøveregion, individ, opptaksdato, eller status på hjernens aktivitetsnivå ved undersøkelsestidspunktet. I den andre studien foreslås en metode for å utføre utforskende analyser av flerdimensjonale fysiologiske data i motsatt ende av den romlig-temporale skalaen, nemlig på populasjonsnivå. En effektiv arbeidsflyt for utforskende dataanalyse må kritisk identifisere interessante mønstre og relasjoner, noe som blir stadig vanskeligere når dimensjonaliteten til dataene øker. Selv om dette delvis kan løses med eksisterende reduksjonsteknikker er det alltid en fare for at subtile mønstre kan gå tapt i reduksjonsprosessen. Isteden presenterer vi i studien DimLift, en iterativ dimensjonsreduksjonsteknikk som muliggjør brukeridentifikasjon av interessante mønstre og relasjoner som kan ligge subtilt i et datasett gjennom dimensjonale bunter. Nøkkelen til denne metoden er brukerens evne til å styre dimensjonalitetsreduksjonen slik at den følger brukerens egne undersøkelseslinjer. For videre å undersøke kommunikasjon til eksperter og ikke-eksperter, studeres i neste arbeid utformingen av visualiseringer for kommunikasjon til publikum med ulike nivåer av ekspertnivå. Det er naturlig å forvente at eksperter innen et emne kan ha ulike preferanser og kriterier for å vurdere en visuell kommunikasjon i forhold til et ikke-ekspertpublikum. Dette påvirker hvor effektivt et bilde kan benyttes til å formidle en gitt scenario. Med utgangspunkt i ulike teknikker innen biomedisinsk illustrasjon og visualisering, gjennomførte vi derfor en utforskende studie av kriteriene som publikum bruker når de evaluerer en biomedisinsk prosessvisualisering målrettet for kommunikasjon. Fra denne studien identifiserte vi muligheter for ytterligere konvergens av biomedisinsk illustrasjon og visualiseringsteknikker for mer målrettet visuell kommunikasjonsdesign. Særlig beskrives i større dybde utviklingen av semantisk konsistente retningslinjer for farging av molekylære scener. Hensikten med slike retningslinjer er å heve den vitenskapelige kompetansen til ikke-ekspertpublikum innen molekyler visualisering, som vil være spesielt relevant for kommunikasjon til befolkningen i forbindelse med folkehelseopplysning. All kode og empiriske funn utviklet i arbeidet med denne avhandlingen er åpen kildekode og tilgjengelig for gjenbruk av det vitenskapelige miljøet og offentligheten. Metodene og funnene presentert i denne avhandlingen danner et grunnlag for tverrfaglig biomedisinsk illustrasjon og visualiseringsforskning, og åpner flere muligheter for fortsatt arbeid med visualisering av fysiologiske prosesser.The overarching theme of this thesis is the cross-disciplinary application of medical illustration and visualization techniques to address challenges in exploring, analyzing, and communicating aspects of physiology to audiences with differing expertise. Describing the myriad biological processes occurring in living beings over time, the science of physiology is complex and critical to our understanding of how life works. It spans many spatio-temporal scales to combine and bridge the basic sciences (biology, physics, and chemistry) to medicine. Recent years have seen an explosion of new and finer-grained experimental and acquisition methods to characterize these data. The volume and complexity of these data necessitate effective visualizations to complement standard analysis practice. Visualization approaches must carefully consider and be adaptable to the user's main task, be it exploratory, analytical, or communication-oriented. This thesis contributes to the areas of theory, empirical findings, methods, applications, and research replicability in visualizing physiology. Our contributions open with a state-of-the-art report exploring the challenges and opportunities in visualization for physiology. This report is motivated by the need for visualization researchers, as well as researchers in various application domains, to have a centralized, multiscale overview of visualization tasks and techniques. Using a mixed-methods search approach, this is the first report of its kind to broadly survey the space of visualization for physiology. Our approach to organizing the literature in this report enables the lookup of topics of interest according to spatio-temporal scale. It further subdivides works according to any combination of three high-level visualization tasks: exploration, analysis, and communication. This provides an easily-navigable foundation for discussion and future research opportunities for audience- and task-appropriate visualization for physiology. From this report, we identify two key areas for continued research that begin narrowly and subsequently broaden in scope: (1) exploratory analysis of multifaceted physiology data for expert users, and (2) communication for experts and non-experts alike. Our investigation of multifaceted physiology data takes place over two studies. Each targets processes occurring at different spatio-temporal scales and includes a case study with experts to assess the applicability of our proposed method. At the molecular scale, we examine data from magnetic resonance spectroscopy (MRS), an advanced biochemical technique used to identify small molecules (metabolites) in living tissue that are indicative of metabolic pathway activity. Although highly sensitive and specific, the output of this modality is abstract and difficult to interpret. Our design study investigating the tasks and requirements for expert exploratory analysis of these data led to SpectraMosaic, a novel application enabling domain researchers to analyze any permutation of metabolites in ratio form for an entire cohort, or by sample region, individual, acquisition date, or brain activity status at the time of acquisition. A second approach considers the exploratory analysis of multidimensional physiological data at the opposite end of the spatio-temporal scale: population. An effective exploratory data analysis workflow critically must identify interesting patterns and relationships, which becomes increasingly difficult as data dimensionality increases. Although this can be partially addressed with existing dimensionality reduction techniques, the nature of these techniques means that subtle patterns may be lost in the process. In this approach, we describe DimLift, an iterative dimensionality reduction technique enabling user identification of interesting patterns and relationships that may lie subtly within a dataset through dimensional bundles. Key to this method is the user's ability to steer the dimensionality reduction technique to follow their own lines of inquiry. Our third question considers the crafting of visualizations for communication to audiences with different levels of expertise. It is natural to expect that experts in a topic may have different preferences and criteria to evaluate a visual communication relative to a non-expert audience. This impacts the success of an image in communicating a given scenario. Drawing from diverse techniques in biomedical illustration and visualization, we conducted an exploratory study of the criteria that audiences use when evaluating a biomedical process visualization targeted for communication. From this study, we identify opportunities for further convergence of biomedical illustration and visualization techniques for more targeted visual communication design. One opportunity that we discuss in greater depth is the development of semantically-consistent guidelines for the coloring of molecular scenes. The intent of such guidelines is to elevate the scientific literacy of non-expert audiences in the context of molecular visualization, which is particularly relevant to public health communication. All application code and empirical findings are open-sourced and available for reuse by the scientific community and public. The methods and findings presented in this thesis contribute to a foundation of cross-disciplinary biomedical illustration and visualization research, opening several opportunities for continued work in visualization for physiology.Doktorgradsavhandlin

Immersive Visualization in Biomedical Computational Fluid Dynamics and Didactic Teaching and Learning

Virtual reality (VR) can stimulate active learning, critical thinking, decision making and improved performance. It requires a medium to show virtual content, which is called a virtual environment (VE). The MARquette Visualization Lab (MARVL) is an example of a VE. Robust processes and workflows that allow for the creation of content for use within MARVL further increases the userbase for this valuable resource. A workflow was created to display biomedical computational fluid dynamics (CFD) and complementary data in a wide range of VE’s. This allows a researcher to study the simulation in its natural three-dimensional (3D) morphology. In addition, it is an exciting way to extract more information from CFD results by taking advantage of improved depth cues, a larger display canvas, custom interactivity, and an immersive approach that surrounds the researcher. The CFD to VR workflow was designed to be basic enough for a novice user. It is also used as a tool to foster collaboration between engineers and clinicians. The workflow aimed to support results from common CFD software packages and across clinical research areas. ParaView, Blender and Unity were used in the workflow to take standard CFD files and process them for viewing in VR. Designated scripts were written to automate the steps implemented in each software package. The workflow was successfully completed across multiple biomedical vessels, scales and applications including: the aorta with application to congenital cardiovascular disease, the Circle of Willis with respect to cerebral aneurysms, and the airway for surgical treatment planning. The workflow was completed by novice users in approximately an hour. Bringing VR further into didactic teaching within academia allows students to be fully immersed in their respective subject matter, thereby increasing the students’ sense of presence, understanding and enthusiasm. MARVL is a space for collaborative learning that also offers an immersive, virtual experience. A workflow was created to view PowerPoint presentations in 3D using MARVL. A resulting Immersive PowerPoint workflow used PowerPoint, Unity and other open-source software packages to display the PowerPoint presentations in 3D. The Immersive PowerPoint workflow can be completed in under thirty minutes

Differential atrial performance at rest and exercise in athletes: Potential trigger for developing atrial dysfunction?

International audienc