The Virtual Physiological Human: Ten Years After

Biomedical research and clinical practice are struggling to cope with the growing complexity that the progress of health care involves. The most challenging diseases, those with the largest socioeconomic impact (cardiovascular conditions; musculoskeletal conditions; cancer; metabolic, immunity, and neurodegenerative conditions), are all characterized by a complex genotype–phenotype interaction and by a “systemic” nature that poses a challenge to the traditional reductionist approach. In 2005 a small group of researchers discussed how the vision of computational physiology promoted by the Physiome Project could be translated into clinical practice and formally proposed the term Virtual Physiological Human. Our knowledge about these diseases is fragmentary, as it is associated with molecular and cellular processes on the one hand and with tissue and organ phenotype changes (related to clinical symptoms of disease conditions) on the other. The problem could be solved if we could capture all these fragments of knowledge into predictive models and then compose them into hypermodels that help us tame the complexity that such systemic behavior involves. In 2005 this was simply not possible—the necessary methods and technologies were not available. Now, 10 years later, it seems the right time to reflect on the original vision, the results achieved so far, and what remains to be done

Mind the gap: quantification of incomplete ablation patterns after pulmonary vein isolation using minimum path search

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF). A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p<0.05 in both cases), in the processed data. This type of information can be very useful for the optimization and objective assessment of PVI interventions

Functional Imaging and Modeling of the Heart:8th International Conference, FIMH 2015, Maastricht, The Netherlands, June 25-27, 2015. Proceedings

This book constitutes the refereed proceedings of the 8th International Conference on Functional Imaging and Modeling of the Heart, held in Maastricht, The Netherlands, in June 2015. The 54 revised full papers were carefully reviewed and selected from 72 submissions. The focus of the papers is on following topics: function; imaging; models of mechanics; and models of electrophysiology

Functional Imaging and Modeling of the Heart: 8th International Conference, FIMH 2015, Maastricht, The Netherlands, June 25-27, 2015. Proceedings

This book constitutes the refereed proceedings of the 8th International Conference on Functional Imaging and Modeling of the Heart, held in Maastricht, The Netherlands, in June 2015. The 54 revised full papers were carefully reviewed and selected from 72 submissions. The focus of the papers is on following topics: function; imaging; models of mechanics; and models of electrophysiology

2015 Touro College & University System Faculty Publications

This is the 2015 edition of the Faculty Publications Book of the Touro College & University System. It includes all eligible 2015 publication citations of faculty within the Touro College & University System, including New York Medical College (NYMC). It was produced as a joint effort of the Touro College Libraries and the Health Sciences Library at NYMC.https://touroscholar.touro.edu/facpubs/1001/thumbnail.jp

Load-dependent electrophysiological and structural cardiac remodelling studied in ultrathin myocardial slices.

Introduction: Myocardial slices are becoming an established system to study cardiac electrophysiology and pharmacological research and development. Unlike other preparations, cardiac slices are a multicellular preparation that has an intermediate, adequate complexity required for this research. Previous studies have successfully obtained slices from human biopsies and animal models, where the electrical and structural parameters could be maintained for several hours – a process which is comparable to other preparation types. Therefore, we aimed to use left ventricular myocardial slices obtained from rat models of mechanical unloading (HAHLT) and from two models of overload (TAC and SHR), to investigate electrophysiological and structural alterations in these models. Methods: Mechanical unloading was achieved by heterotopic abdominal heart and lung transplantation (HAHLT, 8 weeks) and overload was induced by thoracic aortic constriction (TAC, 10 and 20 weeks) in male Lewis rats. Spontaneous hypertensive rats (SHR) were also used as a second model of overload and were primarily induced by hypertension (3, 12 and 20 months). Brown Norway and Wistar Kyoto rats were used as the control groups for SHR. Myocardial slices from the left ventricle (LV) free wall were cut (300-350 µm thick) tangentially to the epicardial surface using a high-precision slow-advancing Vibratome and were point-stimulated using a multi-electrode array system (MEA), therefore, acquiring field potentials (FPs). Field potential duration (FPD) and conduction velocity (CV) were analysed locally and transmurally across the LV free wall. In addition, FPD heterogeneity within each slice was calculated. For the SHR group, the same slices used for the MEA recording were preserved and used subsequently to measure Cx43, Nav1.5 protein levels and fibrosis. Results: Slices obtained from normal rat hearts that are chronically unloaded were found to develop atrophy at a whole heart level. They showed an increase in FPD and its heterogeneity with preserved conduction properties when compared to controls. In TACs, an in vivo whole heart function assessment confirmed hypertrophy with no signs of cardiac dysfunction. Slices from TAC rats showed an increase in FPD at both 10 and 20 weeks after banding. FPD heterogeneity was increased at 10 weeks but normalised at 20 weeks. Changes in CV properties were observed in this group, showing a faster CV and longitudinal conduction velocity (CVL) at 10 weeks and no change at 20 weeks. Transverse conduction velocity (CVT) was unchanged in the TAC group. In SHRs, however, hypertrophy was confirmed and signs of dysfunction in the aged group (20 months) were observed due to the decrease in EF by 18%, especially when compared to the 12 months group. FPD and its heterogeneity was unchanged in SHR when compared to controls. Disease and age-related abnormalities in CV properties were observed in SHR and these were associated with changes in Cx43, Nav1.5 protein level and fibrosis. Conclusion: Myocardial slices are a suitable multicellular preparation to study electrophysiological remodelling obtained from different rat models of cardiovascular disease. In addition, it was possible to investigate the changes in CV and FPD transmurally in rats using this type of preparation method. Thus, this study supports the use of this multicellular preparation in understanding the mechanisms of cardiac disease and the testing of new treatments and therapeutic targets.Open Acces