Kinematic Modeling of the Determinants of Diastolic Function

Multiple modalities are routinely used in clinical cardiology to determine cardiovascular function, and many of the indexes derived from these modalities are causally interconnected. A correlative approach to cardiovascular function however, where indexes are correlated to disease presence and progression, fails to fully capitalize on the information content of the indexes. Causal quantitative modeling of cardiovascular physiology on the other hand offers a predictive rather than accommodative approach to cardiovascular function determination. In this work we apply a kinematic modeling approach to understanding diastolic function. We discuss novel insights related to the physiological determinants of diastolic function, and define novel causal indexes of diastolic function that go beyond the limitations of current established clinical indexes. Diastolic function is typically characterized by physiologists and cardiologists as being determined by the interplay between chamber stiffness, chamber relaxation/viscoelasticity, and chamber filling volume or load. In this work we provide kinematic modeling based analysis of each of these clinical diastolic function determinants. Considering the kinematic elastic (stiffness) components of filling, we argue for the universality of diastolic suction and define a novel in-vivo equilibrium volume. Application of this novel equilibrium volume in the clinical setting results in a novel approach to determination of global chamber stiffness. Considering the viscoelastic components of filling, we demonstrate the limitations associated with ignoring viscoelastic effects, an assumption often made in the clinical setting. We extend the viscoelastic component of filling into the invasive hemodynamic domain, and demonstrate the causal link between invasively recorded LV pressure and noninvasively recorded transmitral flow by describing a method for extracting flow contours from pressure signals alone. Finally, in considering load, we solve the problem of load dependence in diastolic function analysis. Indeed all traditional clinical indexes of diastolic function are load dependent, and therefore are imperfect indexes of intrinsic diastolic function. Applying kinematic modeling, we derive a load independent index of diastolic function. Validation involves showing that the index is indeed load-independent and can differentiate between control and diastolic dysfunction states. We apply this novel analysis to derive surrogates for filling pressure, and generalize the kinematic modeling approach to the analysis of isovolumic relaxation. To aid widespread adoption of the load independent index, we derive and validate simplified expressions for model-based physiological parameters of diastolic function. Our goal is to provide a causal approach to cardiovascular function analysis based on how things move, to explain prior phenomenological observations of others under a single causal paradigm, to discover `new physiology\u27, facilitate the discovery of more robust indexes of cardiovascular function, and provide a means for widespread adoption of the kinematic modeling approach suitable for the general clinical setting

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs. Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma

Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (\u3e0.9) in a large animal model, with superior performance to vital sign metrics

Quasi-static imaged-based immersed boundary-finite element model of human left ventricle in diastole

SUMMARY: Finite stress and strain analyses of the heart provide insight into the biomechanics of myocardial function and dysfunction. Herein, we describe progress toward dynamic patient-specific models of the left ventricle using an immersed boundary (IB) method with a finite element (FE) structural mechanics model. We use a structure-based hyperelastic strain-energy function to describe the passive mechanics of the ventricular myocardium, a realistic anatomical geometry reconstructed from clinical magnetic resonance images of a healthy human heart, and a rule-based fiber architecture. Numerical predictions of this IB/FE model are compared with results obtained by a commercial FE solver. We demonstrate that the IB/FE model yields results that are in good agreement with those of the conventional FE model under diastolic loading conditions, and the predictions of the LV model using either numerical method are shown to be consistent with previous computational and experimental data. These results are among the first to analyze the stress and strain predictions of IB models of ventricular mechanics, and they serve both to verify the IB/FE simulation framework and to validate the IB/FE model. Moreover, this work represents an important step toward using such models for fully dynamic fluid–structure interaction simulations of the heart

Diastolic function alteration mechanisms in physiologic hypertrophy versus pathologic hypertrophy are elucidated by model-based Doppler E-wave analysis.

Athletic training can result in increased left ventricular (LV) wall thickness, termed physiologic hypertrophy (PhH). By contrast, pathologic hypertrophy (PaH) can be due to hypertension, aortic stenosis, or genetic mutation causing hypertrophic cardiomyopathy (HCM). Because morphologic (LV dimension, wall thickness, mass, etc.) and functional index similarities (LV ejection fraction, cardiac output, peak filling rate, etc.) limit diagnostic specificity, ability to differentiate between PhH and PaH is important. Conventional echocardiographic diastolic function (DF) indexes have limited ability to differentiate between PhH and PaH and cannot provide information on chamber property (stiffness and relaxation). We hypothesized that kinematic model-based DF assessment can differentiate between PhH and PaH and, by providing chamber properties, has even greater value compared with conventional metrics. For validation, we assessed DF in the following three age-matched groups: pathologic (HCM) hypertrophy (PaH, n = 14), PhH (Olympic rowers, PhH, n = 21), and controls (n = 21). Magnetic resonance imaging confirmed presence of both types of hypertrophy and determined LV mass and chamber size. Model-based indexes, chamber stiffness (k), relaxation/viscoelasticity (c), and load (xo) and conventional indexes, Epeak (peak of E-wave), ratio of Epeak to Apeak (E/A), E-wave acceleration time (AT), and E-wave deceleration time (DT) were computed. We analyzed 1588 E waves distributed as follows: 328 (PaH), 672 (athletes), and 588 (controls). Among conventional indexes, Epeak and E-wave DT were similar between PaH and PhH, whereas E/A and E-wave AT were lower in PaH. Model-based analysis showed that PaH had significantly higher relaxation/viscoelasticity (c) and chamber stiffness (k) than PhH. The physiologic equation of motion for filling-based derivation of the model provides a mechanistic understanding of the differences between PhH and PaH

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration