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KCNQ1 S140G 돌연변이 발현과 심실세동과의 상관관계 분석을 위한 컴퓨터 시뮬레이션 연구
정다운,임기무,Jeong, Daun,Lim, Ki Moo 대한의용생체공학회 2017 의공학회지 Vol.38 No.3
Background and aims: The KCNQ1 S140G mutation involved in $I_{ks}$ channel is a typical gene mutation affecting atrial fibrillation. However, despite the possibility that the S140G gene mutation may affect not only atrial but also ventricular action potential shape and ventricular responses, there is a lack of research on the relationship between this mutation and ventricular fibrillation. Therefore, in this study, we analyzed the correlation and the influence of the KCNQ1 S140G mutant gene on ventricular fibrillation through computer simulation studies. Method: This study simulated a 3-dimensional ventricular model of the wild type(WT) and the S140G mutant conditions. It was performed by dividing into normal sinus rhythm simulation and reentrant wave propagation simulation. For the sinus rhythm, a ventricular model with Purkinje fiber was used. For the reentrant propagation simulation, a ventricular model was used to confirm the occurrence of spiral wave using S1-S2 protocol. Results: The result showed that 41% shortening of action potential duration(APD) was observed due to augmented $I_{ks}$ current in S140G mutation group. The shortened APD contributed to reduce wavelength 39% in sinus rhythm simulation. The shortened wavelength in cardiac tissue allowed re-entrant circuits to form and increased the probability of sustaining ventricular fibrillation, while ventricular electrical propagation with normal wavelength(20.8 cm in wild type) are unlikely to initiate re-entry. Conclusion: In conclusion, KCNQ1 S140G mutation can reduce the threshold of the re-entrant wave substrate in ventricular cells, increasing the spatial vulnerability of tissue and the sensitivity of the fibrillation. That is, S140G mutation can induce ventricular fibrillation easily. It means that S140G mutant can increase the risk of arrhythmias such as cardiac arrest due to heart failure.
피지옴 모델을 이용한 심실의 전기활성시간 분포에 따른 심박출 성능평가
김형균,임기무,Kim, Hyeong-Gyun,Lim, Ki Moo 대한의용생체공학회 2015 의공학회지 Vol.36 No.5
The purpose of the study is to examine the effects of pacemaker location on cardiac pumping efficacy theoretically. We used a three-dimensional finite element cardiac electromechanical model of canine ventricles with models of the circulatory system. Electrical activation time for normal sinus rhythm and artificial pacing in apex, left ventricular free wall, and right ventricular free wall were obtained from electrophysiological model. We applied the electrical activation time maps to the mechanical contraction model and obtained cardiac mechanical responses such as myocardial contractile ATP consumption, stroke work, stroke volume, ejection fraction, and etc. Among three artificial pacing methods, left ventricle pacing showed best performance in ventricular pumping efficacy.
심근 세포의 전기생리학적 특징을 이용한 인공 신경망 기반 약물의 심장독성 평가
유예담,정다운,임기무,Yoo, Yedam,Jeong, Da Un,Marcellinus, Aroli,Lim, Ki Moo 대한의용생체공학회 2021 의공학회지 Vol.42 No.6
Cardiotoxicity assessment of all drugs has been performed according to the ICH guidelines since 2005. Non-clinical evaluation S7B has focused on the hERG assay, which has a low specificity problem. The comprehensive in vitro proarrhythmia assay (CiPA) project was initiated to correct this problem, which presented a model for classifying the Torsade de pointes (TdP)-induced risk of drugs as biomarkers calculated through an in silico ventricular model. In this study, we propose a TdP-induced risk group classifier of artificial neural network (ANN)-based. The model was trained with 12 drugs and tested with 16 drugs. The ANN model was performed according to nine features, seven features, five features as an individual ANN model input, and the model with the highest performance was selected and compared with the classification performance of the qNet input logistic regression model. When the five features model was used, the results were AUC 0.93 in the high-risk group, AUC 0.73 in the intermediate-risk group, and 0.92 in the low-risk group. The model's performance using qNet was lower than the ANN model in the high-risk group by 17.6% and in the low-risk group by 29.5%. This study was able to express performance in the three risk groups, and it is a model that solved the problem of low specificity, which is the problem of hERG assay.
다형 심실빈맥의 예측을 위한 dVm/dt<sub>Max_repol</sub>의 이온채널 전도도에 대한 민감도 분석
정다운,유예담,임기무,Jeong, Da Un,Yoo, Yedam,Marcellinus, Aroli,Lim, Ki Moo 대한의용생체공학회 2022 의공학회지 Vol.43 No.5
Early afterdepolarization (EAD), a significant cause of fatal ventricular arrhythmias including Torsade de Pointes (TdP) in long QT syndromes, is a depolarizing afterpotential at the plateau or repolarization phase in action potential (AP) profile early before completing one pace. AP duration prolongation is related to EAD but is not necessarily accounted for EAD. Several computational studies suggested EAD can form from an abnormality in the late plateau and/or repolarization phase of AP shape. In this sense, we hypothesized the slope during repolarization has the characteristics to predict TdP risk, mainly focusing on the maximum slope during repolarization (dVm/dt<sub>max_repol</sub>). This study aimed to predict the sensitivity of dVm/dt<sub>max_repol</sub> to ion channel conductances as a TdP risk metric through a population simulation considering multiple effects of simultaneous reduction in six ion channel conductances of g<sub>NaL</sub>, g<sub>Kr</sub>, g<sub>Ks</sub>, g<sub>to</sub>, g<sub>K1</sub>, and g<sub>CaL</sub>. Additionally, we verified the availability of dVm/dt<sub>max_repol</sub> for TdP risk prediction through the correlation analysis with qNet, the representative TdP metric. We performed the population simulations based on the methodology of Gemmel et al. using the human ventricular myocyte model of Dutta et al. Among the sixion channel conductances, dVm/dt<sub>max_repol</sub> and qNet responded most sensitively to the change in g<sub>Kr</sub>, followed by g<sub>NaL</sub>. Furthermore, dVm/dt<sub>max_repol</sub> showed a statistically significant high negative correlation with qNet. The dVm/dt<sub>max_repol</sub> values were significantly different according to three TdP risk levels of high, intermediate, and low by qNet (p<0.001). In conclusion, we suggested dVm/dt<sub>max_repol</sub> as a new biomarker metric for TdP risk assessment.
좌심실보조장치의 출구 캐뉼라의 삽관 위치에 따른 혈액관류에 대한 시뮬레이션 연구
지인혁,김형균,임기무,Jee, In Hyeog,Kim, Hyeong Gyun,Lim, Ki Moo 대한의용생체공학회 2015 의공학회지 Vol.36 No.4
Outflow cannulation site of left ventricular assist device(LVAD) chosen by considering anatomical structure of thoracic cavity and vascular system. Though outflow cannulation site influences blood perfusion at each branch, there is no standard rule or quantitative data. In this study, we computed the amount of blood perfusion at each arterial branch numerically according to outflow cannulation sites(ascending aorta, aortic arch, descending aorta). We generated computational meshes to the three-dimensionally reconstructed arterial system. Clinically measured arterial pressure were used for inlet boundary condition, porous media were applied to mimic blood flow resistance. Blood perfusion through left common carotid artery was 2.5 times higher than other cases, and that through right common carotid artery was 1.1 times higher than other branches. Although this is simulation study, will be useful reference data for the clinical study of LVAD which considers blood perfusion efficiency.
권순성(Kwon Soon Sung),임기무(Lim Ki Moo),이정재,심은보(Shim Eun Bo) 대한기계학회 2008 대한기계학회 춘추학술대회 Vol.2008 No.11
In this study, we simulated the atrial arrhythmia numerically. By using electro-physiological model of atrial cell from Nygren et al. and applying reaction-diffusion partial differential equation, we simulated electrical conduction in atrium. A 3-D mesh system representing the human atrium was reconstructed from the surface geometry of atrium. We used a stimulus in the form of an archetype around pulmonary vessels in the left atrium to cause the atrial arrhythmia. The septal atrial tarchycardia was developed after the stimulus.
부정맥 분류를 위한 표준 12 리드 심전도 신호 기반 시간-주파수 특징을 사용한 2 차원 합성곱 신경망의 활용
정다운(Da Un Jeong),임기무(Ki Moo Lim) 한국통신학회 2021 한국통신학회 학술대회논문집 Vol.2021 No.2
본 논문은 표준 12 리드 심전도 신호로부터 심장 부정맥으로 인한 이상 징후를 자동으로 추출하고 정상적인 심전도 신호 외 심방세동, 1 형 방실 차단, 좌각차단, 우각차단, 심방조기수축, 심실조기수축, ST 분절하강 및 상승의 8 가지 심장 부정맥을 분류하기 위한 2 차원 합성곱 신경망 모델을 제안한다. 제안한 모델의 심장 부정맥의 분류 정확도는 78% 이었으며, 최종 F1 score 는 0.74 이였다. 특히, 제안한 모델은 심방세동과 좌각차단 및 우각 차단, 1 형 방실 차단의 예측 시 F1 score 0.8 이상의 높은 정확도로 분류하는 것이 가능하였다.
이승철(Lee Seung Cheol),임기무(Lim Ki Moo),심은보(Shim Eun Bo) 대한기계학회 2008 대한기계학회 춘추학술대회 Vol.2008 No.11
The moyamoya disease is a type of cerebrovascular disease which produces thin abnormal blood vessels like haze in the brain base because the end of internal carotid artery which supplies about 80% of blood is blocked. Regarding this moyamoya disease, the shearing stress and thrombus generation are mentioned as its main causes. This study three-dimensionally implemented the ICA, ACA, and MCA parts of the cerebrovascular configuration related to the moyamoya disease, and analyzed the hydrodynamic phenomenon with the commercial program ADINA. In particular, the correlations between shearing stress and speed distribution according to the branch angle of ACA and MCA. A numerical analysis found that the greater the branch angle of ACA and MCA, the lower the shearing stress and the greater the stationary area of the flow.. Put Abstract text here.