DEVELOPMENT AND IMPLEMENTATION OF NOVEL STRATEGIES TO EXPLOIT 3D ULTRASOUND IMAGING IN CARDIOVASCULAR COMPUTATIONAL BIOMECHANICS

Introduction In the past two decades, major advances have been made in cardiovascular diseases assessment and treatment owing to the advent of sophisticated and more accurate imaging techniques, allowing for better understanding the complexity of 3D anatomical cardiovascular structures1. Volumetric acquisition enables the visualization of cardiac districts from virtually any perspective, better appreciating patient-specific anatomical complexity, as well as an accurate quantitative functional evaluation of chamber volumes and mass avoiding geometric assumptions2. Additionally, this scenario also allowed the evolution from generic to patient-specific 3D cardiac models that, based on in vivo imaging, faithfully represent the anatomy and different cardiac features of a given alive subject, being pivotal either in diagnosis and in planning guidance3. Precise morphological and functional knowledge about either the heart valves\u2019 apparatus and the surrounding structures is crucial when dealing with diagnosis as well as preprocedural planning4. To date, computed tomography (CT) and real-time 3D echocardiography (rt3DE) are typically exploited in this scenario since they allow for encoding comprehensive structural and dynamic information even in the fourth dimension (i.e., time)5,6. However, owing to its cost-effectiveness and very low invasiveness, 3D echocardiography has become the method of choice in most situations for performing the evaluation of cardiac function, developing geometrical models which can provide quantitative anatomical assessment7. Complementing this scenario, computational models have been introduced as numerical engineering tools aiming at adding qualitative and quantitative information on the biomechanical behavior in terms of stress-strain response and other multifactorial parameters8. In particular, over the two last decades, their applications have been ranging from elucidating the heart biomechanics underlying different patho-physiological conditions9 to predicting the effects of either surgical or percutaneous procedures, even comparing several implantation techniques and devices10. At the early stage, most of the studies focused on FE modeling in cardiac environment were based on paradigmatic models11\u201315, being mainly exploited to explore and investigate biomechanical alterations following a specific pathological scenario or again to better understand whether a surgical treatment is better or worse than another one. Differently, nowadays the current generation of computational models heavily exploits the detailed anatomical information yielded by medical imaging to provide patient-specific analyses, paving the way toward the development of virtual surgical-planning tools16\u201319. In this direction, cardiac magnetic resonance (CMR) and CT/micro-CT are the mostly accomplished imaging modality, since they can provide well-defined images thanks to their spatial and temporal resolutions20\u201325. Nonetheless, they cannot be applied routinely in clinical practice, as it can be differently done with rt3DE, progressively became the modality of choice26 since it has no harmful effects on the patient and no radiopaque contrast agent is needed. Despite these advantages, 3D volumetric ultrasound imaging shows intrinsic limitations beyond its limited resolution: i) the deficiency of morphological detail owing to either not so easy achievable detection (e.g., tricuspid valve) or not proper acoustic window, ii) the challenge of tailoring computational models to the patient-specific scenario mimicking the morphology as well as the functionality of the investigated cardiac district (e.g., tethering effect exerted by chordal apparatus in mitral valve insufficiency associated to left ventricular dilation), and iii) the needing to systematically analyse devices performances when dealing with real-life cases where ultrasound imaging is the only performable technique but lacking of standardized acquisition protocol. Main findings In the just described scenario, the main aim of this work was focused on the implementation, development and testing of numerical strategies in order to overcome issues when dealing with 3D ultrasound imaging exploitation towards predictive patient-specific modelling approaches focused on both morphological and biomechanical analyses. Specifically, the first specific objective was the development of a novel approach integrating in vitro imaging and finite element (FE) modeling to evaluate tricuspid valve (TV) biomechanics, facing with the lack of information on anatomical features owing to the clinically evident demanding detection of this anatomical district through in vivo imaging. \u2022 An innovative and semi-automated framework was implemented to generate 3D model of TV, to quantitively describe its 3D morphology and to assess its biomechanical behaviour. At this aim, an image-based in vitro experimental approach was integrated with numerical models based on FE strategy. Experimental measurements directly performed on the benchmark (mock circulation loop) were compared with geometrical features computed on the 3D reconstructed model, pinpointing a global good consistency. Furthermore, obtained realistic reconstructions were used as the input of the FE models, even accounting for proper description of TV leaflets\u2019 anisotropic mechanical response. As done experimentally, simulations reproduced both \u201cincompetent\u201d (FTR) and \u201ccompetent-induced\u201d (PMA), proving the efficiency of such a treatment and suggesting translational potential to the clinic. The second specific aim was the implementation of a computational framework able to reproduce a functionally equivalent model of the mitral valve (MV) sub-valvular apparatus through chordae tendineae topology optimization, aiming at chordae rest length arrangement to be able to include their pre-stress state associated to specific ventricular conformation. \u2022 We sought to establish a framework to build geometrically tractable, functionally equivalent models of the MV chordae tendineae, addressing one of the main topics of the computational scientific literature towards the development of faithful patient-specific models from in vivo imaging. Exploiting the mass spring model (MSM) approach, an iterative tool was proposed aiming to the topology optimization of a paradigmatic chordal apparatus of MVs affected by functional regurgitation, in order to be able to equivalently account for tethering effect exerted by the chordae themselves. The results have shown that the algorithm actually lowered the error between the simulated valve and ground truth data, although the intensity of this improvement is strongly valve-dependent.Finally, the last specific aim was the creation of a numerical strategy able to allow for patient-specific geometrical reconstruction both pre- and post- LVAD implantation, in a specific high-risk clinical scenario being rt3DE the only available imaging technique to be used but without any acquisition protocol. \u2022 We proposed a numerical approach which allowed for a systematic and selective analysis of the mechanism associated to intraventricular thrombus formation and thrombogenic complications in a LVAD-treated dilated left ventricle (LV). Ad-hoc geometry reconstruction workflow was implemented to overcome limitations associated to imaging acquisition in this specific scenario, thus being able to generate computational model of the LV assisted with LVAD. In details, results suggested that blood stasis is influenced either by LVAD flow rate and, to a greater extent, by LV residual contractility, being the positioning of the inflow cannula insertion mandatory to be considered when dealing with LVAD thrombogenic potential assessment

A Comprehensive Review of Techniques for Processing and Analyzing Fetal Heart Rate Signals

The availability of standardized guidelines regarding the use of electronic fetal monitoring (EFM) in clinical practice has not effectively helped to solve the main drawbacks of fetal heart rate (FHR) surveillance methodology, which still presents inter- and intra-observer variability as well as uncertainty in the classification of unreassuring or risky FHR recordings. Given the clinical relevance of the interpretation of FHR traces as well as the role of FHR as a marker of fetal wellbeing autonomous nervous system development, many different approaches for computerized processing and analysis of FHR patterns have been proposed in the literature. The objective of this review is to describe the techniques, methodologies, and algorithms proposed in this field so far, reporting their main achievements and discussing the value they brought to the scientific and clinical community. The review explores the following two main approaches to the processing and analysis of FHR signals: traditional (or linear) methodologies, namely, time and frequency domain analysis, and less conventional (or nonlinear) techniques. In this scenario, the emerging role and the opportunities offered by Artificial Intelligence tools, representing the future direction of EFM, are also discussed with a specific focus on the use of Artificial Neural Networks, whose application to the analysis of accelerations in FHR signals is also examined in a case study conducted by the authors

Oral application of L-menthol in the heat: From pleasure to performance

When menthol is applied to the oral cavity it presents with a familiar refreshing sensation and cooling mint flavour. This may be deemed hedonic in some individuals, but may cause irritation in others. This variation in response is likely dependent upon trigeminal sensitivity toward cold stimuli, suggesting a need for a menthol solution that can be easily personalised. Menthol’s characteristics can also be enhanced by matching colour to qualitative outcomes; a factor which can easily be manipulated by practitioners working in athletic or occupational settings to potentially enhance intervention efficacy. This presentation will outline the efficacy of oral menthol application for improving time trial performance to date, either via swilling or via co-ingestion with other cooling strategies, with an emphasis upon how menthol can be applied in ecologically valid scenarios. Situations in which performance is not expected to be enhanced will also be discussed. An updated model by which menthol may prove hedonic, satiate thirst and affect ventilation will also be presented, with the potential performance implications of these findings discussed and modelled. Qualitative reflections from athletes that have implemented menthol mouth swilling in competition, training and maximal exercise will also be included

Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease

Objectives: To assess the clinical effectiveness and cost-effectiveness, in different patient groups, of the use of 64-slice or higher computed tomography (CT) angiography, instead of invasive coronary angiography (CA), for diagnosing people with suspected coronary artery disease (CAD) and assessing people with known CAD. Data sources: Electronic databases were searched from 2002 to December 2006. Review methods: Included studies were tabulated and sensitivity, specificity, positive and negative predictive values calculated. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. Summary sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for each model were reported as a median and 95% credible interval (CrI). Searches were also carried out for studies on the cost-effectiveness of 64-slice CT in the assessment of CAD. Results: The diagnostic accuracy and prognostic studies enrolled over 2500 and 1700 people, respectively. The overall quality of the studies was reasonably good. In the pooled estimates, 64-slice CT angiography was highly sensitive (99%, 95% CrI 97 to 99%) for patientbased detection of significant CAD (defined as 50% or more stenosis), while across studies the negative predictive value (NPV) was very high (median 100%, range 86 to 100%). In segment-level analysis compared with patient-based detection, sensitivity was lower (90%, 95% CrI 85 to 94%, versus 99%, 95% CrI 97 to 99%) and specificity higher (97%, 95% CrI 95 to 98%, versus 89%, 95% CrI 83 to 94%), while across studies the median NPV was similar (99%, range 95 to 100%, versus 100%, range 86 to 100%). At individual coronary artery level the pooled estimates for sensitivity ranged from 85% for the left circumflex (LCX) artery to 95% for the left main artery, specificity ranged from 96% for both the left anterior descending (LAD) artery and LCX to 100% for the left main artery, while across studies the positive predictive value (PPV) ranged from 81% for the LCX to 100% for the left main artery and NPV was very high, ranging from 98% for the LAD (range 95 to 100%), LCX (range 93 to 100%) and right coronary artery (RCA) (range 94 to 100%) to 100% for the left main artery. The pooled estimates for bypass graft analysis were 99% (95% CrI 95 to 100%) sensitivity, 96% (95% CrI 86 to 99%) specificity, with median PPV and NPV values across studies of 93% (range 90 to 95%) and 99% (range 98 to 100%), respectively. This compares with, for stent analysis, a pooled sensitivity of 89% (95% CrI 68 to 97%), specificity 94% (95% CrI 83 to 98%), and median PPV and NPV values across studies of 77% (range 33 to 100%) and 96% (range 71 to 100%), respectively. Sixty-four-slice CT is almost as good as invasive CA in terms of detecting true positives. However, it is somewhat poorer in its rate of false positives. It seems likely that diagnostic strategies involving 64-slice CT will still require invasive CA for CT test positives, partly to identify CT false positives, but also because CA provides other information that CT currently does not, notably details of insertion site and distal run-off for possible coronary artery bypass graft (CABG). The high sensitivity of 64-slice CT avoids the costs of unnecessary CA in those referred for investigation but who do not have CAD. Given the possible, although small, associated death rate, avoiding these unnecessary CAs through the use of 64-slice CT may also confer a small immediate survival advantage. This in itself may be sufficient to outweigh the very marginally inferior rates of detection of true positives by strategies involving 64-slice CT. The avoidance of unnecessary CA through the use of 64-slice CT also appears likely to result in overall cost savings in the diagnostic pathway. Only if both the cost of CA is relatively low and the prevalence of CAD in the presenting population is relatively high (so that most patients will go on to CA) will the use of 64-slice CT be likely to result in a higher overall diagnostic cost per patient. Conclusions: The main value of 64-slice CT may at present be to rule out significant CAD. It is unlikely to replace CA in assessment for revascularisation of patients, particularly as angiography and angioplasty are often done on the same occasion. Further research is needed into the marginal advantages and costs of 256-slice machines compared with 64-sliceCT, the usefulness of 64-slice CT in people with suspected acute coronary syndrome, the potential of multislice computed tomography to examine plaque morphology, the role of CT in identifying patients suitable for CABG, and the concerns raised about repetitive use, or use of 64-slice or higher CT angiography in younger individuals or women of childbearing age.The Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen, is core-funded by the Chief Scientist Office of the Scottish Government Health Directorates