原口 亮

In recent years, echocardiography is a common tool for diagnosing congenital heart disease because it is non-invasive and it provides real-time imaging. However, it is necessary to have specialized knowledge and experience to analyze the three-dimensional anatomical structure of the heart from 2-D echocardiography. Currently, experts on echocardiography explain the diagnosis of the patient to another medical staff by using two-dimensional schematic illustrations. The sharing of complex information about the diagnosis is time-consuming and difficult. We propose a heart chambers editing interface for three-dimensional modeling of congenital heart diseases. In order to facilitate interactivity, the center-position and radius of the heart chamber are used to edit the shape of the heart chambers (atriums and ventricles). In other words, the heart chambers are expressed in spherical coordinates. We provide a shape-editing interface for modifying the surface of the heart chambers. In addition, we provide a topology-editing interface to connect/disconnect between the heart chambers with each other or the heart chamber and the great vessel. Using our system, we can visualize some types of congenital heart diseases, such as ventricular septal defect, and double-outlet right ventricle. In our preliminary user study, experts verified that the constructed three-dimensional model of our proposed system is useful for representing the relationship and positioning between the heart chambers and the great vessels. Therefore, our developed system enables us to easily and quickly construct a three-dimensional heart model to facilitate the sharing of information on the diseases among medical staff.

Previously, we developed of an online support system for persons with metabolic syndrome. In this study, we investigated the possibility of enhancing our system for applications in ischemic heart disease (IHD) and heart failure (HF). The main causes of IHD are obesity, hypertension, arteriosclerosis, hyperglycemia and other metabolic disorders. These conditions are related to lifestyle issues, such as diet and exercise. Dietary management becomes more difficult as the patient's condition worsens. We primarily focused on behavior changes. To raise the user's awareness of food intake, we improved a number of functions of the developed system: an entry of the user's lifestyle information, a calculation of the total calorie intake and a reference of food model pictures in 80 kcal standard quantities. IHD encompasses many of the causes of HF. Management tools appropriate for HF are few. We describe the main functions of our system and promote self-management as a requirement for IHD and HF. We expect that the framework of our system is applicable to the management of patients with chronic HF.

The atrioventricular (AV) node, which is located between the atria and ventricles of the heart, acts as important roles in cardiac excitation conduction between the two chambers. Although there are multiple conduction pathways in the AV node, the structure of the AV node has not been clarified. In this study, we constructed a one-dimensional model of the AV node and simulated excitation conduction between the right atrium and the bundle of His via the AV node. We also investigated several characteristics of the AV node: (1) responses of the AV node to high-rate excitation in the right atrium, (2) the AV nodal reentrant beat induced by premature stimulus, and (3) ventricular rate control during atrial fibrillation with various methods. Our simulation results suggest that multiple conduction pathways act as important roles in controlling the ventricular rate. The one-dimensional model constructed in this study may be useful to analyze complex conduction patterns in the AV node.

Computer simulation techniques for cardiac beating motions potentially have many applications and a broad audience. However, most existing methods require enormous computational costs and often show unstable behavior for extreme parameter sets, which interrupts smooth simulation study and make it difficult to apply them to interactive applications. To address this issue, we present an efficient and robust framework for simulating the cardiac beating motion. The global cardiac motion is generated by the accumulation of local myocardial fiber contractions. We compute such local-to-global deformations using a kinematic approach; we divide a heart mesh model into overlapping local regions, contract them independently according to fiber orientation, and compute a global shape that satisfies contracted shapes of all local regions as much as possible. A comparison between our method and a physics-based method showed that our method can generate motion very close to that of a physics-based simulation. Our kinematic method has high controllability; the simulated ventricle-wall-contraction speed can be easily adjusted to that of a real heart by controlling local contraction timing. We demonstrate that our method achieves a highly realistic beating motion of a whole heart in real time on a consumer-level computer. Our method provides an important step to bridge a gap between cardiac simulations and interactive applications.

The World Health Organization reported that ischemic heart disease is the most common cause of death worldwide in 2008. The main causes of ischemic heart disease are obesity, hypertension, arteriosclerosis and other metabolic abnormalities. These conditions are related to lifestyle issues, such as diet and exercise. We developed a system to support the self-management of patients using a personal digital assistant (PDA). However, diet management becomes more difficult as patient condition worsens. Both self-management and behavior change by persons with metabolic syndrome are needed to prevent ischemic heart disease. In the present study, we have improved the system to support behavior change in persons with metabolic syndrome. The system has three functions of an entry of user's lifestyle information, a calculation of total amount of calorie intake and a reference to food model pictures of 80 kcal standard quantities for the behavior change. We focused on a self-review of user lifestyle as the first step of the behavior change. We conducted an experiment with the cooperation of 14 medical staff members to verify the operability of the system. No serious problems with the system were encountered. Additionally, we tested the system with health checkup examinees. The results of these tests suggested that our system will help physicians provide advice regarding total amount of calorie intake to health checkup examinees.

Rationale: Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear. Objective: Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation. Methods and Results: We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone. Conclusions: Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation. (Circ Res. 2012;110:275-284.)

This paper proposes a 3-D cardiovascular modeling system based on neonatal echocardiographic images. With the system, medical doctors can interactively construct patient-specific cardiovascular models, and share the complex topology and the shape information. For the construction of cardiovascular models with a variety of congenital heart diseases, we propose a set of algorithms and interface that enable editing of the topology and shape of the 3-D models. In order to facilitate interactivity, the centerline and radius of the vessels are used to edit the surface of the heart vessels. This forms a skeleton where the centerlines of blood vessel serve as the nodes and edges, while the radius of the blood vessel is given as an attribute value to each node. Moreover, parent-child relationships are given to each skeleton. They are expressed as the directed acyclic graph, where the skeletons are viewed as graph nodes and the connecting points are graph edges. The cardiovascular models generated from some patient data confirmed that the developed technique is capable of constructing cardiovascular disease models in a tolerable timeframe. It is successful in representing the important structures of the patient-specific heart vessels for better understanding in preoperative planning and electric medical recording of the congenital heart disease.

Advanced clinical diagnosis of a cardiac function requires quantitative evaluation of myocardium deformation. It is however still challenging to quantify myocardium deformations due to noises caused by entire cardiac movements and limits of imaging modalities. Here, we propose a novel method for gaining strain rates of myocardium with better spatiotemporal accuracy compared with conventional methods. The proposed method is based on the theory of geometrical constraints which provides a deformation gradient tensor to relate undeformed to deformed configuration of an object. The deformed configuration of the left ventricle was estimated from the present configuration and velocity data obtained by phase contrast (PC)-MR imaging. The proposed method has two major advantages. First, because of no need to use temporally sequential images in estimating velocity as in conventional methods, strain rates calculated from the proposed method are basically free from temporal resolutions of imaging modalities. Second, because of unnecessity of spatially interpolating data, calculated strain rates retain the same spatial resolution as PC-MR images. On comparing a spatial field of strain rates obtained with the proposed method to that with a conventional method, we found that the proposed method was capable of providing spatially smoother field of strain rates in the left ventricular myocardium.

This paper presents a lightweight sketching system that enables interactive illustration of complex fluid systems. Users can sketch on a 2.5-dimensional (2.5D) canvas to design the shapes and connections of a fluid circuit. These input sketches are automatically analyzed and abstracted into a hydraulic graph, and a new hybrid fluid model is used in the background to enhance the illustrations. The system provides rich simple operations for users to edit the fluid system incrementally, and the new internal flow patterns can be simulated in real time. Our system is used to illustrate various fluid systems in medicine, biology, and engineering. We asked professional medical doctors to try our system and obtained positive feedback from them. © 2011 ACM.

The gap junction and voltage-gated Na+ channel play an important role in the action potential propagation. The purpose of this study was to elucidate the roles of subcellular Na+ channel distribution in action potential propagation. To achieve this, we constructed the myocardial strand model, which can calculate the current via intercellular cleft (electric-field mechanism) together with gap-junctional current (gap-junctional mechanism). We conducted simulations of action potential propagation in a myofiber model where cardiomyocytes were electrically coupled with gap junctions alone or with both the gap junctions and the electric field mechanism. Then we found that the action potential propagation was greatly affected by the subcellular distribution of Na+ channels in the presence of the electric field mechanism. The presence of Na+ channels in the lateral membrane was important to ensure the stability of propagation under conditions of reduced gap-junctional coupling. In the poorly coupled tissue with sufficient Na+ channels in the lateral membrane, the slowing of action potential propagation resulted from the periodic and intermittent dysfunction of the electric field mechanism. The changes in the subcellular Na+ channel distribution might be in part responsible for the homeostatic excitation propagation in the diseased heart.

左心室壁の複雑な運動の特徴を非侵襲的に捉えるために、左心室心筋MR-PC(MR位相コントラスト法)画像から得られる速度情報に対して、幾何制約を用いた変形手法を応用した新しいひずみ速度解析手法を提案し、従来法と比較検討した。健常成人男性1名を被験者とした。幾何制約を用いた変形手法を用いることで、短軸断面図の左心室心筋上のひずみ速度場分布を示すことができた。従来法から得られたひずみ速度分布は、伸展部分と短縮部分がまだら状に混在する傾向がみられた。提案手法で得られたひずみ速度分布では、短軸断面上における左室心筋の半径方向および周方向ひずみ速度から、局所的に伸展している部分と短縮している部分が滑らかに変化していた。

Background: We have recently demonstrated in computer simulations that rotational anisotropy of ventricular fiber orientation decreases the sustainability of ventricular fibrillation (VF) even under the large transmural dispersion of repolarization (TDR). However, how the rotational anisotropy restrains VF is still unclear. Methods: To clarify this issue, we repeated simulations of scroll wave (SW) reentry in ventricular wall slab models, incorporating varying degrees of rotational anisotropy. Transmural gradient (electrical heterogeneity through the wall epi-, midmyo-, and endo-cardial layers) was achieved by modifications of potassium currents. Then, we analyzed the dynamics of both SW and its filament (3-dimensional organizing center of SW). Results: In the control model without rotational anisotropy, larger TDR increased the difference of SW cycle lengths among the layers. Then such asynchronous SW meandering destabilized the transmural I-shaped filament, causing filament fragmentation, i.e., VF. In contrast, as the degree of rotational anisotropy increased, the I-shaped filament became more stable, preventing the degeneration into VF. Conclusions: Large TDR and rotational anisotropy increase independently the SW complexity however, such combinations might prevent transition of stable SW to chaotic VF via the control of SW filament. Our finding might contribute to clarify the physiological significance of rotational anisotropy in ventricles. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Rate control to limit conduction from the atrium to the ventricle during AF is one of the important treatments clinically. However, the ionic basis underlying the rate control is not clear. In this study, we have investigated the effect of antiarrhythmic drugs on ventricular rate using mathematical model. Methods: We constructed one-dimensional model for rabbit with two conduction pathways from the atrium to the bundle of His. To simulate AF, the string of atrial cells was stimulated randomly. Ca2+ antagonists are known effective in rate control in patients with AF. To simulate this, Ca2+ current was decreased. Effect of Na+ channel blocker that is not always used clinically was also simulated. Results: When Ca2+ current was partially blocked during AF, excitation rate in a slow pathway was decreased resulting in slow ventricular rate. When the Na+ current was partially suppressed, rate in the slow pathway was not changed, but decreased in a fast pathway. As a result, ventricular rate was also decreased. Conclusion: Although antiarrhythmic drugs for blocking either Na+ and Ca2+ currents could control ventricular response by modulating atrioventricular conduction, there are two different mechanisms to control ventricular rate during AF. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Cardiac sodium (Na+) channels play critical roles in initiating and propagating action potentials in myocardium. We have recently reported that the action potential propagation was greatly affected by the subcellular distribution of Na+ channels in a physiologically-relevant myofiber model, where myocytes were electrically coupled with both gap-junctions and intercellular cleft conductor. Here, we extended the simulation to the initiation of phase-2 reentry in Brugada syndrome. We conducted computer simulations of action potential propagation in the myofiber model, and investigated the effect of spatial and subcellular distributions of Na+ channels on the phase-2 reentry. In the myofiber model with local decrease in Na+ current density, phase-2 reentry was not reproduced. Surprisingly, in the same myofiber model but with a certain type of subcellular Na+ channel remodeling (all Na+ channels were distributed only in the intercalated disks and there were no Na+ channels along the lateral side of each myocyte), the local decrease in Na+ current density resulted in the marked abbreviation of the action potential duration followed by phase-2 reentry. Changes in subcellular Na+ channel distribution in addition to the spatially-heterogeneous Na+ channel density might be required for fibrillation induction in Brugada syndrome. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Background: We have recently demonstrated in computer simulations that electrotonic interactions between atrial myocytes and heterogeneously-distributed fibroblasts result in the genesis of complex fractionated atrial electrograms (CFAEs) during chronic atrial fibrillation (AF). However, previous research has not provided sufficient evidence that ablation targeting such fibroblast-derived CFAEs can terminate AF. Methods: To clarify this issue, we repeated simulations of CFAE-targeted ablation in the model of human chronic AF under heart failure, and we analyzed details of the excitation propagation until the AF was terminated by the application of CFAE-targeted ablation. Results: (1) Sustained spiral wave reentry, as a model of chronic AF, was found to terminate earlier as the number of ablation sites increased. (2) CFAE-targeted ablation site transiently pinned the spiral wave, preventing wave breakup by blocking the shortcut of the reentry. (3) The spiral wave drifted between ablation sites, and after a short time the spiral wave was pushed out of the CFAE area, resulting in AF termination. (4) For more effective CFAE-targeted ablation, avoiding collagen accumulation area and keeping an appropriate distance between ablation sites were required. Conclusion: Our findings might contribute to better understanding of the mechanisms of CFAE-targeted AF ablation. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Background: There are many studies to investigate mechanisms of induction and maintenance of ventricular fibrillation (VF) however, the mechanisms have not been clarified yet. It is known that the thickness of ventricular wall varies with time during VF i.e., thickness of left ventricular wall is increased whereas that of right ventricular wall is decreased. We hypothesized that such deformation of ventricular walls during VF alters the stability of VF. To clarify this issue, we conducted computer simulation of VF in the ventricular wall slab models deformed with time. Methods: We constructed slab models with 10-mm thickness for left ventricular wall and with 5-mm thickness for right ventricular wall. Electrical heterogeneity and rotational anisotropy through the ventricular wall were included. After the onset of VF, thicknesses of the slabs were varied dynamically. The scroll wave filament (3-dimensional reentrant center) was expressed as a continuum of phase singularities. Results: In the deforming right ventricular wall, filament trajectory on the epicardial surface was gradually decreased, confirming stability of the scroll wave reentry. In the deforming left ventricular wall, filament was separated into several parts and filament trajectories traced complicated patterns. In contrast, the scroll waves without deformation were terminated by the annihilation of all filaments. Conclusion: Deforming ventricular walls during VF play important roles to maintain VF. © 2011, Japanese Heart Rhythm Society. All rights reserved.

This paper proposes a three-dimensional cardiovascular model construction system. With the system, medical doctors can interactively construct patient-specific cardiovascular models from echocardiographic images. For the construction of cardiovascular models with diverse and complex congenital heart illness, the system proposes a set of algorithms and interface that enable editing of the shape and topology of the three-dimensional models. In order to facilitate interactivity during the construction of the cardiovascular models, centerline and radius are added to the surface of the heart vessels. This forms a skeleton where the centerlines of blood vessel serve as the nodes and edges, while the radius of the blood vessel is given as an attribute value to each node. Moreover, parent-child relationships are given to each skeleton. They are expressed as the directed acyclic graph, where the skeletons are viewed as graph nodes and the connecting points are graph edges. The results of cardiovascular model construction using real patient data confirmed that the developed technique is capable of constructing cardiovascular models in a tolerable timeframe. Thus, it is suitable for practical use. Moreover, it is successful in representing the important structures of the patient-specific heart vessels for better understanding of the congenital heart disease. Therefore, the developed system enables well representation to the congenital heart disease, which is diagnosed by medical doctors through echocardiography.

実世界に起きる現象はきわめて複雑であり、理論的にその振る舞いを解析したり、あるいは記述したりするのは容易なことではない。特に、心室細動に代表される致死性不整脈のような複雑な心電現象を、単純なモデル化や数式化により理解することは困難である。コンピュータシミュレーションおよび可視化は、その複雑なメカニズムの整理や直感的な理解のためには有効な手段である。心臓の電気的特性は、多種のイオンチャネルが複雑に関連しながら機能して決定される心筋細胞の電気活動、さらにそれらの心筋細胞が3次元的に配列し有機的に協調・連携した臓器というように階層性を持ったシステムの特性として決定される。したがって、不整脈現象をより正確に理解するには、心臓をシステムとして捉える工学的視点が要求され、心臓の電気現象の各階層(イオンチャネル/心筋細胞/心臓)を統合して考える必要がある。国立循環器病研究センターを中心に進められているプロジェクトでは、スーパーコンピュータを用いた高速大規模計算技術、コンピュータグラフィックスによる表示、医用画像処理など、さまざまな工学的技術が含まれている。心臓モデルを用いたコンピュータシミュレーションを中心に、われわれの研究グループにおける一連の不整脈研究を示す。(著者抄録)