Nonequilibrium arrhythmic states and transitions in a mathematical model for diffuse fibrosis in human cardiac tissue

We present a comprehensive numerical study of spiral-and scroll-wave dynamics in a state-of-the-art mathematical model for human ventricular tissue with fiber rotation, transmural heterogeneity, myocytes, and fibroblasts. Our mathematical model introduces fibroblasts randomly, to mimic diffuse fibrosis, in the ten Tusscher-Noble-Noble-Panfilov (TNNP) model for human ventricular tissue; the passive fibroblasts in our model do not exhibit an action potential in the absence of coupling with myocytes; and we allow for a coupling between nearby myocytes and fibroblasts. Our study of a single myocyte-fibroblast (MF) composite, with a single myocyte coupled to N-f fibroblasts via a gap-junctional conductance G(gap), reveals five qualitatively different responses for this composite. Our investigations of two-dimensional domains with a random distribution of fibroblasts in a myocyte background reveal that, as the percentage P-f of fibroblasts increases, the conduction velocity of a plane wave decreases until there is conduction failure. If we consider spiral-wave dynamics in such a medium we find, in two dimensions, a variety of nonequilibrium states, temporally periodic, quasiperiodic, chaotic, and quiescent, and an intricate sequence of transitions between them; we also study the analogous sequence of transitions for three-dimensional scroll waves in a three-dimensional version of our mathematical model that includes both fiber rotation and transmural heterogeneity. We thus elucidate random-fibrosis-induced nonequilibrium transitions, which lead to conduction block for spiral waves in two dimensions and scroll waves in three dimensions. We explore possible experimental implications of our mathematical and numerical studies for plane-, spiral-, and scroll-wave dynamics in cardiac tissue with fibrosis.

Quantitative estimation of mechanical and optical properties from ultrasound assisted optical tomography data

We demonstrate quantitative optical property and elastic property imaging from ultrasound assisted optical tomography data. The measurements, which are modulation depth M and phase phi of the speckle pattern, are shown to be sensitively dependent on these properties of the object in the insonified focal region of the ultrasound (US) transducer. We demonstrate that Young's modulus (E) can be recovered from the resonance observed in M versus omega (the US frequency) plots and optical absorption (mu(a)) and scattering (mu(s)) coefficients from the measured differential phase changes. All experimental observations are verified also using Monte Carlo simulations. (c) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). DOI: 10.1117/1.JBO.17.10.101507]

Diffusing-wave spectroscopy in an inhomogeneous object: Local viscoelastic spectra from ultrasound-assisted measurement of correlation decay arising from the ultrasound focal volume

We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a viscoelastically inhomogeneous object by measurement of the intensity autocorrelation g(2)(tau)] that captures only the decay introduced by the temperature-induced Brownian motion in the region. The region is roughly specified by the focal volume of an ultrasound transducer which introduces region specific mechanical vibration owing to insonification. Essential characteristics of the localized non-Markovian dynamics are contained in the decay of the modulation depth M(tau)], introduced by the ultrasound forcing in the focal volume selected, on g(2)(tau). The modulation depth M(tau(i)) at any delay time tau(i) can be measured by short-time Fourier transform of g(2)(tau) and measurement of the magnitude of the spectrum at the ultrasound drive frequency. By following the established theoretical framework of DWS, we are able to connect the decay in M(tau) to the mean-squared displacement (MSD) of scattering centers and the MSD to G*(omega), the complex viscoelastic spectrum. A two-region composite polyvinyl alcohol phantom with different viscoelastic properties is selected for demonstrating local DWS-based recovery of G*(omega) corresponding to these regions from the measured region specific M(tau(i))vs tau(i). The ultrasound-assisted measurement of MSD is verified by simulating, using a generalized Langevin equation (GLE), the dynamics of the particles in the region selected as well as by the usual DWS experiment without the ultrasound. It is shown that whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed with its experimental counterpart covering small and large values of tau, the match was good only in the initial transients in regard to experimental measurements with ultrasound.

Intense Acoustic Burst Ultrasound Modulated Optical Tomography for Elasticity Mapping of Soft Biological Tissue Mimicking Phantom: A Laser Speckle Contrast Analysis Study

This report addresses the assessment of variation in elastic property of soft biological tissues non-invasively using laser speckle contrast measurement. The experimental as well as the numerical (Monte-Carlo simulation) studies are carried out. In this an intense acoustic burst of ultrasound (an acoustic pulse with high power within standard safety limits), instead of continuous wave, is employed to induce large modulation of the tissue materials in the ultrasound insonified region of interest (ROI) and it results to enhance the strength of the ultrasound modulated optical signal in ultrasound modulated optical tomography (UMOT) system. The intensity fluctuation of speckle patterns formed by interference of light scattered (while traversing through tissue medium) is characterized by the motion of scattering sites. The displacement of scattering particles is inversely related to the elastic property of the tissue. We study the feasibility of laser speckle contrast analysis (LSCA) technique to reconstruct a map of the elastic property of a soft tissue-mimicking phantom. We employ source synchronized parallel speckle detection scheme to (experimentally) measure the speckle contrast from the light traversing through ultrasound (US) insonified tissue-mimicking phantom. The measured relative image contrast (the ratio of the difference of the maximum and the minimum values to the maximum value) for intense acoustic burst is 86.44 % in comparison to 67.28 % for continuous wave excitation of ultrasound. We also present 1-D and 2-D image of speckle contrast which is the representative of elastic property distribution.

Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue

Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model fast inward Na+ current (INa), L-type slow inward Ca2+ current (I-CaL), slow delayed-rectifier current (I-Ks), rapid delayed-rectifier current (I-Kr), inward rectifier K+ current (I-K1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is similar to 2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

Ultrasound-modulated optical tomography: direct recovery of elasticity distribution from experimentally measured intensity autocorrelation

Based on an ultrasound-modulated optical tomography experiment, a direct, quantitative recovery of Young's modulus (E) is achieved from the modulation depth (M) in the intensity autocorrelation. The number of detector locations is limited to two in orthogonal directions, reducing the complexity of the data gathering step whilst ensuring against an impoverishment of the measurement, by employing ultrasound frequency as a parameter to vary during data collection. The M and E are related via two partial differential equations. The first one connects M to the amplitude of vibration of the scattering centers in the focal volume and the other, this amplitude to E. A (composite) sensitivity matrix is arrived at mapping the variation of M with that of E and used in a (barely regularized) Gauss-Newton algorithm to iteratively recover E. The reconstruction results showing the variation of E are presented. (C) 2015 Optical Society of America

Lesion Detection in Breast Ultrasound Images Using Tissue Transition Analysis

Breast cancer is one of the leading cause of cancer related deaths in women and early detection is crucial for reducing mortality rates. In this paper, we present a novel and fully automated approach based on tissue transition analysis for lesion detection in breast ultrasound images. Every candidate pixel is classified as belonging to the lesion boundary, lesion interior or normal tissue based on its descriptor value. The tissue transitions are modeled using a Markov chain to estimate the likelihood of a candidate lesion region. Experimental evaluation on a clinical dataset of 135 images show that the proposed approach can achieve high sensitivity (95 %) with modest (3) false positives per image. The approach achieves very similar results (94 % for 3 false positives) on a completely different clinical dataset of 159 images without retraining, highlighting the robustness of the approach.

Detection and estimation of liquid flow through a pipe in a tissue-like object with ultrasound-assisted diffuse correlation spectroscopy

Using coherent light interrogating a turbid object perturbed by a focused ultrasound (US) beam, we demonstrate localized measurement of dynamics in the focal region, termed the region-of-interest (ROI), from the decay of the modulation in intensity autocorrelation of light. When the ROI contains a pipe flow, the decay is shown to be sensitive to the average flow velocity from which the mean-squared displacement (MSD) of the scattering centers in the flow can be estimated. While the MSD estimated is seen to be an order of magnitude higher than that obtainable through the usual diffusing wave spectroscopy (DWS) without the US, it is seen to be more accurate as verified by the volume flow estimated from it. It is further observed that, whereas the MSD from the localized measurement grows with time as tau(alpha) with alpha approximate to 1.65, without using the US, a is seen to be much less. Moreover, with the local measurement, this super-diffusive nature of the pipe flow is seen to persist longer, i.e., over a wider range of initial tau, than with the unassisted DWS. The reason for the super-diffusivity of flow, i.e., alpha < 2, in the ROI is the presence of a fluctuating (thermodynamically nonequilibrium) component in the dynamics induced by the US forcing. Beyond this initial range, both methods measure MSDs that rise linearly with time, indicating that ballistic and near-ballistic photons hardly capture anything beyond the background Brownian motion. (C) 2015 Optical Society of America

Prior image based temporally constrained reconstruction algorithm for magnetic resonance guided high intensity focused ultrasound

Purpose: A prior image based temporally constrained reconstruction ( PITCR) algorithm was developed for obtaining accurate temperature maps having better volume coverage, and spatial, and temporal resolution than other algorithms for highly undersampled data in magnetic resonance (MR) thermometry. Methods: The proposed PITCR approach is an algorithm that gives weight to the prior image and performs accurate reconstruction in a dynamic imaging environment. The PITCR method is compared with the temporally constrained reconstruction (TCR) algorithm using pork muscle data. Results: The PITCR method provides superior performance compared to the TCR approach with highly undersampled data. The proposed approach is computationally expensive compared to the TCR approach, but this could be overcome by the advantage of reconstructing with fewer measurements. In the case of reconstruction of temperature maps from 16% of fully sampled data, the PITCR approach was 1.57x slower compared to the TCR approach, while the root mean square error using PITCR is 0.784 compared to 2.815 with the TCR scheme. Conclusions: The PITCR approach is able to perform more accurate reconstructions of temperature maps compared to the TCR approach with highly undersampled data in MR guided high intensity focused ultrasound. (C) 2015 American Association of Physicists in Medicine.