Depth-resolved optical imaging of transmural electrical propagation in perfused heart

Hillman, Elizabeth M. C.; Bernus, Olivier; Pease, Emily; Bouchard, Michael J.; Pertsov, Arkady M.

doi:10.1364/oe.15.017827

Cited by 72 publications

(62 citation statements)

References 31 publications

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“…All other parameter values are as described in the original model (31). The model equations were solved using a forward Euler method with an adaptive time step varying between 0.001 and 0.01 ms as in a previous study (18) . Action potentials were obtained after pacing the model cell at 5 Hz for 10 s. Restitution curves were simulated using an S1-S2 stimulation protocol consisting of 20 S1 pulses at a 200-ms cycle length and an S2 pulse at a gradually decreasing coupling interval from 200 ms down to 40 ms in decrements of 10 ms.…”

Section: Methodsmentioning

confidence: 99%

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

Benoist

Stones

Drinkhill

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Benoist D, Stones R, Drinkhill M, Bernus O, White E. Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. Am J Physiol Heart Circ Physiol 300: H2230 -H2237, 2011. First published March 11, 2011 doi:10.1152/ajpheart.01226.2010.-Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K ϩ channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy. electrical restitution; fibrillation; action potentials INCREASED PULMONARY ARTERIAL pressure increases loading on the right ventricle (RV), which can lead to electrical, mechanical, and structural remodeling. In humans, pulmonary artery hypertension (PAH) is a disease that can be unstable and RV failure is a common outcome (4, 13, 38). The QT interval and QT dispersion of the ECG have been reported to be increased (19,20), and the shift in ECG derived ventricular gradient [reflecting action potential duration (APD) dispersion] has been related to increased RV load (17). Such changes in electrical activity have been linked to arrhythmias (1, 39), and PAH is associated with arrhythmias in patients (11). RV pathophysiology is in general understudied compared with the left ventricle (LV; Ref. 38), and the mechanisms that underlie RV changes in electrical activity in response to hypertension are not well understood.The monocrotaline (MCT)-induced model of pulmonary arterial hypertension and RV hypertrophy is well established (e.g., Refs. 14, 23). MCT is a pyrrolizidine alkaloid from...

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Section: Methodsmentioning

confidence: 99%

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

Benoist

Stones

Drinkhill

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…These optical methods, developed on experimental preparations using various species, have recently been applied to the ex vivo human heart [20,21]. More recently, novel optical methods have been proposed that allow the recording of propagating activity within the ventricular wall and that achieve depth-resolved optical imaging using tomographical approaches [22][23][24][25]. Theory, experiments and clinical studies all lead to an explanation of ventricular excitation and arrhythmias in terms of the hidden spatio-temporal patterns of propagation within the ventricular wall.…”

Section: Introductionmentioning

confidence: 99%

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

et al. 2010

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Reaction -diffusion computational models of cardiac electrophysiology require both dynamic excitation models that reconstruct the action potentials of myocytes as well as datasets of cardiac geometry and architecture that provide the electrical diffusion tensor D, which determines how excitation spreads through the tissue. We illustrate an experimental pipeline we have developed in our laboratories for constructing and validating such datasets. The tensor D changes with location in the myocardium, and is determined by tissue architecture. Diffusion tensor magnetic resonance imaging (DT-MRI) provides three eigenvectors e i and eigenvalues l i at each voxel throughout the tissue that can be used to reconstruct this architecture. The primary eigenvector e 1 is a histologically validated measure of myocyte orientation (responsible for anisotropic propagation). The secondary and tertiary eigenvectors (e 2 and e 3 ) specify the directions of any orthotropic structure if l 2 is significantly greater than l 3 -this orthotropy has been identified with sheets or cleavage planes. For simulations, the components of D are scaled in the fibre and cross-fibre directions for anisotropic simulations (or fibre, sheet and sheet normal directions for orthotropic tissues) so that simulated conduction velocities match values from optical imaging or plunge electrode experiments. The simulated pattern of propagation of action potentials in the models is partially validated by optical recordings of spatio-temporal activity on the surfaces of hearts. We also describe several techniques that enhance components of the pipeline, or that allow the pipeline to be applied to different areas of research: Q ball imaging provides evidence for multi-modal orientation distributions within a fraction of voxels, infarcts can be identified by changes in the anisotropic structure-irregularity in myocyte orientation and a decrease in fractional anisotropy, clinical imaging provides human ventricular geometry and can identify ischaemic and infarcted regions, and simulations in human geometries examine the roles of anisotropic and orthotropic architecture in the initiation of arrhythmias.

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“…LOT has a resolution of ~100 µm with 2-3 mm penetration depths [40][41][42][43][44][45], which is comparable to the imaging depth of OCT, as well as the size of typical biopsy and histology. LOT imaging of skin cancer based on absorption contrast has been demonstrated [46].…”

Section: Introductionmentioning

confidence: 98%

“…Laminar optical tomography (LOT) is a promising approach to overcome this limitation by using multiple detectors to collect lights travelling through different depths, and through mathematical de-convolution to reconstruct the depth-resolved image [40][41][42]. LOT has a resolution of ~100 µm with 2-3 mm penetration depths [40][41][42][43][44][45], which is comparable to the imaging depth of OCT, as well as the size of typical biopsy and histology.…”

Section: Introductionmentioning

confidence: 99%

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography

Tang

Wang

Frank

et al. 2016

Biomed. Opt. Express

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Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is difficult to detect the subsurface lesions. In this research, we investigated the feasibility of a novel multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. The C57BL/6J-Apc Min /J mice were imaged using OCT and FLOT, and the correlated histopathological diagnosis was obtained. Quantitative structural (scattering coefficient) and molecular (relative enzyme activity) parameters were obtained from OCT and FLOT images for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 88.23% (82.35%) for sensitivity (specificity) compared to either modality alone. This study suggested that combining OCT and FLOT is promising for subsurface cancer detection, diagnosis, and characterization. Muthasamy, C. J. Lightdale, N. Santiago, D. K. Pleskow, P. J. Dean, and K. K. Wang, "Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial," Endoscopy 42(10), 781-789 (2010 cancer lesion with swept-source optical coherence tomography," J.

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Depth-resolved optical imaging of transmural electrical propagation in perfused heart

Cited by 72 publications

References 31 publications

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography

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