The Genetically Modified Polysialylated Form of Neural Cell Adhesion Molecule-Positive Cells for Potential Treatment of X-Linked Adrenoleukodystrophy

PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.ope

Application of 222-nm Krypton-Chlorine Excimer Lamp to Control Foodborne Pathogens

학위논문(박사)--서울대학교 대학원 :농업생명과학대학 농생명공학부,2019. 8. 강동현.유엔 환경 계획 (the United Nations Environment Program, UNEP)이 수은의 사용을 점차적으로 없애기 위해 2020년부터 발효되는 미나마타 협약을 체결함에 따라, 기존의 수은을 함유하는 자외선 (Ultraviolet, UV) 램프를 대체하기 위한 새로운 자외선 조사 시스템의 적용이 필요한 실정이다. 현재, 유전체 장벽 방전 (Dielectric barrier discharge, DBD) 구동 엑시머 램프는 파장 선택성, 긴 수명, 빠른 예열, 높은 방사 세기 및 수은 부재의 특징으로 향후 수은 램프를 대체할 잠재적인 대안 기술로 여겨지고 있다. 본 논문에서는, 식중독균을 제어하는 기술로써 222-nm 크립톤-염소 (KrCl) 엑시머 램프의 적용 가능성을 확인하였으며, 구체적인 목표는 (i) 식중독균에 대한 222-nm KrCl 엑시머 램프의 저감화 메커니즘 규명, (ii) 주스 내 식중독균 제어를 위한 222-nm KrCl 엑시머 램프 적용, (iii) 농산물 표면 위 식중독균 제어를 위한 222-nm KrCl 엑시머 램프 적용이다. 222-nm KrCl 엑시머 램프의 저감화 기작은 몇가지 세포 손상을 분석함으로써 조사되었다. 222-nm KrCl 엑시머램프는 세포막 손상을 탈분극의 형태로 유도하는 것으로 나타났다. 이 형태의 세포막 손상은 세포막 전위 발생과 관련이 있는 효소의 불활성화 및 세포막의 지질과산화에 의해 유도되었다. 비록 254-nm 수은 자외선 램프에 의한 데미지 보다는 적었지만, 222-nm KrCl 엑시머 램프는 DNA에도 데미지를 발생시켰다. 광반응을 일으키는 자외선의 직접적인 흡수는 세포 손상을 유도하는 원인 중 하나 될 수 있다. 더하여, 222-nm의 활성산소 (reactive oxygen species, ROS)의 생성과 이에 따른 2차적 손상의 발생 또한 세포 손상을 유도하는 또 다른 원인이 될 수 있다. 222-nm KrCl 엑시머램프의 기본적인 저감화 원리를 이해하고 난 후, 이 기술을 식품 내 식중독균 제어를 위해 적용하여 보았다. 우선, 주스 내 병원성균에 대한 222-nm KrCl 엑시머램프의 저감화 효과를 평가하였다. 이 때, 주스의 낮은 pH 조건이 식중독균에 산 적응 반응 (acid adaptation response)을 유도하여 222-nm KrCl 엑시머램프 처리에 대한 저항성 변화를 일으키는지 여부를 조사하였다. 산에 적응된 식중독균과 산에 적응되지 않은 식중독균 (Escherichia coli O157:H7, Salmonella Typhimurium)은 염산 (HCl)으로 pH가 5.0으로 조절된 덱스트로스가 없는 트립톤 소이 배지 (Tryptone soy broth without dextrose, TSB w/o D)와 pH 7.3의 TSB w/o D에 각각 성장시켜 유도하였다. 사과주스 내의 산에 적응된 식중독균에 대한 222-nm KrCl 엑시머램프의 D5d값 [5-log 감소를 달성하기 위해 필요한 에너지 투입량 (mJ/cm2)]은 산에 적응되지 않은 식중독균에 대한 D5d 값보다 유의적으로 (P < 0.05) 더 큰 값을 나타내었다. 기작 규명을 통해서, 세포막의 포화지방산에 대한 불포화지방산의 비율 (불포화지방산/포화지방산)이 산 적응의 결과로 유의적 (P < 0.05)으로 감소하였기 때문에, 산성 적응 식중독균의 세포막에서 222-nm KrCl 엑시머램프 처리에 의한 세포막 파괴를 유도하는 지질 과산화의 생성이 산에 적응되지 않은 식중독균의 세포막에서보다 유의적으로 (P < 0.05) 더 적게 발생한 것을 확인하였다. 산 적응으로 식중독균의 저항성이 증가하였지만, 222-nm KrCl 엑시머램프는 사과주스의 품질 변화 없이 산 적응 식중독균을 5-log 감소 시켰다. 주스 산업에서 222-nm KrCl 엑시머 램프가 더욱 효과적으로 활용될 수 있게 하기 위해서, 조합 기술을 222-nm KrCl 엑시머 램프에 적용하여 보았다. 이 때, 222-nm KrCl 엑시머 램프는 온열 (mild heating) 처리와 조합되었으며, 식중독균에 대한 이 조합 처리의 제어 효과를 조사하였다. 45, 50, 또는 55oC의 온열 처리와 222-nm KrCl 엑시머 램프의 동시 처리는 사과 주스 내의 산 적응 식중독균에 대해서 상승적 (synergistic) 저감화 효과를 나타내었다. 이 조합 처리의 상승적 저감화 기작은 몇가지 분석을 통해 규명되었으며, 다음과 같이 설명될 수 있다. (1) 222-nm KrCl 엑시머 램프와 온열이 동시에 처리될 때, 온열 처리는 슈퍼옥사이드 디스뮤테이즈 (superoxide dismutase, SOD)를 가역적으로 불활성화 시켜 222-nm KrCl 엑시머 램프가 생성하는 ROS의 축적을 증가시켜 상승적 ROS 발생을 유도한다. (2) ROS의 상승적 생성은 세포막에서 지질 과산화의 상승적 발생을 일으킨다. (3) 세포막의 지질 과산화의 상승적 발생은 세포막의 상승적 파괴로 이어져 결국 세포의 상승적 사멸을 유도한다. 45, 50, 또는 55oC의 온열 처리와 222-nm KrCl 엑시머 램프의 조합 처리가 산에 적응된 식중독균을 5-log 감소시키는 동안 사과주스의 유의적인 (P > 0.05) 품질 변화는 나타나지 않았다. 두번째로, 222-nm KrCl 엑시머 램프의 신선농산물 (사과 및 파프리카) 표면의 식중독균에 대한 제어 효과를 조사하였다. 자외선의 투과율이 낮아 사과 및 파프리카 표면의 병원성균에 대한 222-nm KrCl 엑시머 램프의 저감화 효과는 1.5 log 미만이었다. 이러한 한계를 극복하기 위해, 샘플 표면의 미생물을 탈리하는 Spindle과 222-nm KrCl 엑시머 램프를 결합하여 신선 농산물을 세척하는 시스템 (Sp-Ex)을 개발하였으며, 이것의 식중독균 제어 효과를 조사하였다. 식중독균 (E. coli O157:H7, S. Typhimurium, L. monocytogenes)의 초기 농도는 108 CFU/sample 이었다. E. coli O157:H7 및 S. Typhimurium은 모두 사과 및 파프리카 표면에서 각각 5분 및 7분 처리 후 검출 한계 (= 2.0 log CFU/sample) 이하로 검출되었다. 사과 및 파프리카 표면의 L. monocytogenes는 7분 처리 후에 각각 4.26 및 5.48 log 감소하였다. Sp-Ex의 식중독균 제어효과는 세포 표면의 소수성뿐 아니라 샘플 표면의 소수성에 영향을 받으며, 이 소수성이 증가할수록 Sp-Ex의 제어 효과가 감소하였다. Sp-Ex의 제어 효과를 향상시키기 위해서, 소수성 상호작용을 약화시키는 계면활성제인 TWEEN 20을 Sp-Ex 처리에 적용하였다. 그 결과, 0.1 % TWEEN 20의 첨가로 Sp-Ex의 식중독균 제어 효과가 유의적 (P 0.05) 품질 변화는 발생시키지 않았다. 결론적으로, 이 연구의 결과는 222-nm KrCl 엑시머 램프가 식품 산업에서 식중독균을 제어하기 위한 수단으로 적용될 수 있는 다양한 적용 전략을 제시한다. 또한, 제어 원리의 분석 결과는 식품 산업 및 관련된 추후 연구에 유용한 기초 자료로 활용될 수 있을 것으로 기대된다.As the United Nations Environment Program (UNEP) has signed the Minamata convention on Mercury, which aims to gradually eliminate the usage of mercury, which will enter into force in 2020, the application of a new ultraviolet (UV) system to replace conventional mercury-containing UV lamp has become necessary. Currently, dielectric barrier discharge (DBD)-driven excilamps are considered a potential alternative technology to mercury UV lamps in the future because of their characteristics of wavelength selectivity, long lifetime, fast warm-up, high radiant intensity, and absence of mercury. In this thesis, the applicability of 222-nm krypton-chlorine (KrCl) excilamp among several excilamps as a technology to control foodborne pathogens in food was identified, and specific objective of this study were, (i) identification of inactivation mechanism of 222-nm KrCl excilamp against foodborne pathogens, (ii) application of 222-nm KrCl excilamp to control pathogens in juice product, and (iii) application of 222-nm KrCl excilamp to control pathogens on fresh produce surface. The bactericidal mechanism of the 222-nm KrCl excilamp was investigated by analyzing several cellular damage. It was found out that the 222-nm KrCl excilamp induced cell membrane damage as a form of depolarization. This cell membrane damage was attributed to inactivation of enzymes related to generation of membrane potential and occurrence of lipid peroxidation. Although less than the damage caused by 254-nm low-pressure (LP) mercury (Hg) lamp, 222-nm KrCl excilamp also caused damage to DNA. Direct absorption of UV radiation which led to photoreaction was one of the causes inducing cell damage. Additionally, generation of ROS by 222-nm and thus occurrence of secondary damage can be another cause. After understanding the basic bactericidal principle of 222-nm KrCl excilamp, this technology was applied to the control of pathogens in food products. First, the inactivation effect of 222-nm KrCl excilamp on the pathogens in the juice product was evaluated. At this time, it was examined whether the low pH condition of the juice induces acid adaptation response to pathogens and cause a change in resistance to 222-nm KrCl excilamp treatment. Acid adapted- and non-acid adapted pathogens (E. coli O157:H7 and S. Typhimurium) were induced by growing the cells in TSB without dextrose (TSB w/o D) at pH 7.3 and TSB w/o D at pH 5.0 adjusted with HCl, respectively. For the KrCl excilamp treatment, acid-adapted pathogens exhibited significantly (P < 0.05) higher D5d values, which indicate dosages required for achieving 5-log reduction, than non-acid adapted pathogens in commercially clarified apple juice. Through mechanism identification, it was found that the generation of lipid peroxidation in cell membrane, inducing cell membrane destruction, of acid adapted cells was significantly (P < 0.05) less than that of non-acid adapted cells for the same amount of reactive oxygen species (ROS) generated at the same dose because the ratio of unsaturated to saturated fatty acids (USFA/SFA) in the cell membrane was significantly (P < 0.05) decreased as a result of acid adaptation. Even though the acid adaptation increased the resistance of pathogens, the 222-nm KrCl excilamp achieved 5-log reduction without changing the quality of apple juice. The combination technology was applied to 222-nm KrCl excilamp to make it more effectively utilized to control pathogen in juice industry. At this time, 222-nm KrCl excilamp was combined with mild heating and its control effect on pathogens in apple juice was investigated. As a result, simultaneous treatment with 222-nm KrCl excilamp and mild heating (EX-MH) at 45, 50 and 55oC showed synergistic bactericidal effects on acid adapted pathogens in apple juice. The elucidation of the synergistic bactericidal mechanism of EX-MH was performed through several assays and this mechanism was described as follows: (1) when 222-nm KrCl excilamp (EX) and mild heating (MH) are applied simultaneously, MH reversibly inactivates the antioxidant enzyme superoxide dismutase (SOD), thereby increasing accumulation of reactive oxygen species (ROS) generated by EX and thus inducing synergistic ROS generation, (2) synergistic generation of ROS induces synergistic occurrence of lipid peroxidation in the cell membrane, (3) synergistic occurrence of lipid peroxidation in the cell membrane induces synergistic destruction of cell membrane, resulting in synergistic cell death. Furthermore, after EX-MH treatment at 45, 50, or 55oC for time intervals shown to reduce acid adapted cells of E. coli O157:H7 (the pathogen most resistant to EX-MH) by 5-log, there were no significant (P > 0.05) changes in apple juice quality. Secondly, the effect of 222-nm KrCl excilamp on inactivation of pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes) on fresh produces [apple (Malus domestica Borkh.) and bell pepper (Capsicum annuum L.)] surfaces was investigated. Due to the low transmittance characteristic of UV, the inactivation effects of 222-nm KrCl excilamp on pathogens on the surface of solid food (apple and bell pepper) were less than 1.5 log reduction. To overcome this limitation, a washing system capable of decontaminating fresh produce by combining the Spindle, which detaches microorganisms on that sample surfaces, and a 222-nm KrCl excilamp (Sp-Ex) was developed, and their decontamination effect was investigated. Initial levels of the three pathogens were approximately 108 CFU/sample. Both E. coli O157:H7 and S. Typhimurium were reduced to below the detection limit (= 2.0 log CFU/sample) after 5 and 7 min treatment on apple and bell pepper surfaces, respectively. L. monocytogenes on apple and bell pepper surface were reduced by 4.26 and 5.48 log, respectively, after 7 min treatment. The decontamination effect of the Sp-Ex was influenced by the hydrophobicity of the sample surface as well as the microbial cell surface, and the decontamination effect decreased as the two hydrophobicity values increased. To improve the decontamination effect of the Sp-Ex, TWEEN 20, a surfactant that weakens the hydrophobic interaction between the sample surface and pathogenic bacteria was incorporated into Sp-Ex processing. As a result, it was found that its decontamination effect was significantly (P 0.05) quality changes in apple or bell pepper surfaces during storage of 7 days following treatment. In conclusion, the results of this thesis suggest various application strategies for the 222-nm KrCl excilamp to be applied as a means for controlling foodborne pathogens in the food industry. In addition, it is expected that the analysis of the control principle can be effectively utilized as a baseline data for practical application in the food industry and for further related studies.Chapter I. Inactivation mechanism of 222 nm krypton-chlorine (KrCl) excilamp irradiation on gram-positive and gram-negative foodborne pathogenic bacteria 1 I-1. Introduction. 2 I-2. Materials and Methods. 7 Bacterial cultures and cell suspension 7 Experimental apparatus and treatment . 8 Bacterial enumeration 9 Enumeration of injured cells 9 Analysis of inactivation mechanisms. 10 (i) Modeling of survival curves . 11 (ii) Membrane potential assay . 11 (iii) Detection of the end products of lipid peroxidation. 12 (iv) Detection of Intracellular ROS 13 (v) DNA damage assay. 14 (vi) Enzymatic activity assay 15 Statistical analysis 16 I-3. Results and Discussion. 17 Chapter II. Application of 222-nm KrCl excilamp to control foodborne pathogens in juice product 41 Chapter II-1. Increased resistance of Salmonella Typhimurium and Escherichia coli O157:H7 to 222-nm krypton-chlorine excilamp treatment by acid adaptation. 42 II-1.1. Introduction. 43 II-1.2. Materials and Methods 49 Bacterial strains 49 Preparation of non-acid- and acid adapted bacterial culture and inoculum 49 UV treatment . 50 Bacterial enumeration 55 Enumerations of sub-lethally injured cells. 55 Modeling of survival curves and calculation of D5d 56 Measurement of incidence of cell membrane damage and generation of intracellular ROS . 58 Analysis of fatty acid composition of cell membrane. 59 Quality measurement. 60 Statistical analysis 62 II-1.3. Results. 63 Comparative resistance of acid adapted- and non-acid adapted cells of S. Typhimurium and E. coli O157:H7 to 222-nm KrCl excilamp treatment 63 Incidence of the cell membrane damage and intracellular ROS generation during 222-nm KrCl excilamp treatment 70 Changes in fatty acid composition of the cell membrane 76 Observation of apple juice quality during 222-nm KrCl excilamp treatment 78 II-1.4. Discussion. 80 Chapter II-2. Synergistic effect of 222-nm krypton-chlorine excilamp and mild heating combined treatment on inactivation of Escherichia coli O157:H7 and Salmonella Typhimurium in apple juice 91 II-2.1. Introduction. 92 II-2.2. Materials and Methods 99 Bacterial strains and culture preparation. 99 EX, MH, or EX-MH Treatment 100 Bacterial cell enumeration 101 Modeling of survival curve and calculation of T5d 102 Analysis of mechanism of synergistic bactericidal effect. 103 (i) Investigation of cell membrane damage. 103 (ii) Measurement of total reactive oxygen species (ROS) and Superoxide (O2-) generation. 105 (iii) Measurement of SOD activity 106 Measurement of quality indicators . 107 Statistical analysis 108 II-2.3. Results and Discussion 110 Bactericidal effect of 222-nm KrCl excilamp, mild heating, or combination treatment on pathogens in apple juice 109 Identification of mechanisms of synergistic bactericidal effect of EX-MH treatment. 122 (i) Cell membrane damage 122 (ii) Occurrence of intracellular ROS and O2- 131 (iii) Activity of superoxide dismutase (SOD). 136 Comparing color, TPC, DPPH free radical scavenging activity of apple juice after EX-MH . 140 Conclusion. 142 Chapter III. Decontamination effect of the Spindle and 222-nm krypton-chlorine excilamp combination against pathogens on fresh produce surface 144 III-1. Introduction. 145 III-2. Materials and Methods 150 Bacterial strains and inoculum preparation 150 Sample preparation and inoculation 150 Experimetal setup. 151 Treatment. 154 Bacterial enumeration 154 Cell surface hydrophobicity of pathogens 156 Surface characteristic analysis . 157 Color and texture measurement 158 Statistical analysis 158 III-3. Results and Discussion 160 The effect of individual 222-nm KrCl excilamp and Spindle treatment on pathogen inactivation on sample surfaces 160 The decontamination effect of Sp-Ex treatment . 166 Factors affecting decontamination effect of the Sp-Ex. 169 Enhanced decontamination effect of the Sp-Ex by adding surfactant. 176 Effect of the Sp-Ex on apple and bell pepper quality. 180 Conclusion. 180 References 184 국문 초록. 229Docto

An experimental feasibility study of free-breathing diffusion tensor imaging in porcine acute myocardial infarction model

학위논문 (박사)-- 서울대학교 대학원 : 의학과 영상의학 전공, 2013. 8. 이활.서론: 확산텐서자기공명영상은 심근 경색환자에서 심근 섬유 배열의 재형성을 보여주는 지표일 뿐 아니라 심근 구조를 비침습적으로 보여줄 수 있는 방법으로 주목을 받고 있는 기법이다. 하지만, 생체 내 심장 확산텐서영상법은 심장 및 호흡으로 인한 움직임으로 인해 일반화되지 않고 있으며, 대부분의 생체 내 심장 확산텐서영상법은 호흡을 정지한 상태에서 시행되고 있다. 이 연구의 목적은 생체 내에서 호흡을 멈추지 않고 시행하는 확산텐서영상의 유용성을 평가하려는 것이다. 방법: 30kg 몸무게의 요크셔 돼지 16 마리를 전신마취 하에 개흉술을 시행하고, 좌전하행 관상동맥의 중간부를 결찰하여 급성심근경색을 유도하였다. 이후, 1.5 tesla 자장의 기기를 이용해 자기공명영상 검사를 시행하여 T2 강조영상 및 지연기 조영증강영상을 통해 급성심근경색의 발생 여부와 발생 부위를 확인하였다. 이어서, navigator 기법과 심전도 동기화를 이용하여 호흡을 멈추지 않고 시행하는 확산텐서영상검사를 시행하였다. B 값은 300s/mm2로 하여 6방향의 확산경사자장을 이용해 심장의 중간부위에서 8 mm의 절편두께를 이용해 확산텐서영상을 획득하였다. 얻어진 영상의 품질을 좋음, 보통, 나쁨의 3 단계로 평가하였다. 이 후, 경색심근 부위와 정상 심근 부위에서 현성확산계수(apparent diffusion coefficient)로 표현되는 평균 확산도(mean diffusivity) 및 이방성, 그리고, 추적된 섬유의 길이(fiber length) 를 정량적으로 분석하였다. 현성확산계수와 이방성은 두 번 측정하여, 관측 값들 사이의 일치도를 분석하였다. 결과: 16 마리 중 7 마리 돼지에서 급성심근경색을 유도하여 생체 내 심장 확산텐서영상을 얻었으며, 확산텐서영상 획득에는 8 1.5 분이 소요되었다. 확산텐서영상의 품질은 좋음 3 마리, 보통 2 마리, 나쁨 2 마리였다. 급성심근경색 부위는 정상부위보다 현성확산계수가 유의하게 증가되어 있었다(8.097 ± 3.741 10-3 mm2/sec 대 5.894 ± 2.985 10-3 mm2/sec, P=0.018). 이방성의 경우 급성심근경색부위가 정상부위보다 유의하게 감소되어 있었다(0.393 0.972 대 0.485 0.145, P=0.018). 추적된 섬유의 길이는 심근경색부위에서 정상부위보다 유의하게 짧았다(17.57 5.46 mm 대 24.84 9.79 mm, P=0.018). 현성확산계수와 이방성 을 두 번 측정한 관측 값들 간의 차이는 통계적으로 유의하지 않았다. 결론: 호흡을 멈추지 않고 시행한 생체 내 확산텐서영상에서 보통 이상의 품질의 영상을 71.4% (7 마리 중 5 마리)에서 얻을 수 있고, 호흡 정지 상태 혹은 적출 심장에서 얻은 현성확산계수 및 이방성의 확산텐서영상 연구결과와 일치하였다. 따라서, 이 기법을 이용하여, 호흡 조절이 힘든 환자에게 있어서도 심근경색 후 정상과 경색 심근 사이의 구조의 차이를 보여줄 수 있어, 검사의 적응증을 확대할 수 있을 것이다.초 록 i 목 차 iv 표 및 그림 목록 v 서 론 1 실험재료 및 방법 4 연구 결과 17 고 찰 41 결 론 47 참고문헌 48 Abstract 55Docto

콩과수목에서 분리한 근류군의 다양성과 계통분류

Thesis (master`s)--서울대학교 대학원 :산림자원학과,2003.Maste

정합을 이용한 Visible Human 자료 골격계 자동 분할의 유용성 연구 : 두부와 하지의 적용

학위논문(석사)--서울대학교 대학원 :의학과 방사선과학전공,2003.Maste

HFC125/Propane 혼합냉매의 기-액 상평형에 관한 실험적 연구

학위논문(석사)--아주대학교 대학원 :기계공학과,2002Maste

Late Gadolinium Enhancement of Left Ventricular Papillary Muscles in Patients with Mitral Regurgitation

Objective: Arrhythmogenic mitral valve prolapse (MVP) is an important cause of sudden cardiac death characterized by fibrosis of the papillary muscles or left ventricle (LV) wall, and an association between late gadolinium enhancement (LGE) of the LV papillary muscles and ventricular arrhythmia in MVP has been reported. However, LGE of the papillary muscles may be observed in other causes of mitral regurgitation, and it is not limited to patients with MVP. This study was to evaluate the association of LGE of the LV papillary muscles or ventricular wall on cardiac magnetic resonance imaging (CMR) and ventricular arrhythmia in patients with mitral regurgitation. Materials and Methods: This study included 88 patients (mean age +/- standard deviation, 58.3 +/- 12.0 years; male, 42%) with mitral regurgitation who underwent CMR. They were allocated to the MVP (n = 43) and non-MVP (n = 45) groups, and their LGE images on CMR, clinical characteristics, echocardiographic findings, and presence of arrhythmia were compared. Results: LV myocardial wall enhancement was more frequent in the MVP group than in the non-MVP group (28% vs. 11%, p = 0.046). Papillary muscle enhancement was observed in 7 (7.9%) patients. Of the 43 patients with MVP, 15 (34.8%) showed LGE in the papillary muscles or LV myocardium, including 12 (27.9%) with LV myocardial wall enhancement and 4 (9.3%) with papillary muscle enhancement. One patient with bilateral diffuse papillary muscle enhancement experienced sudden cardiac arrest due to ventricular fibrillation. Univariable logistic regression analysis showed that high systolic blood pressure (BP; odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = 0.027) and ventricular arrhythmia (OR, 6.84; 95% CI, 1.29-36.19; p = 0.024) were significantly associated with LGE of the papillary muscles. Conclusion: LGE of the papillary muscles was present not only in patients with MVP, but also in patients with other etiologies of mitral regurgitation, and it was associated with high systolic BP and ventricular arrhythmia. Papillary muscle enhancement on CMR should not be overlooked

Fully Automatic Coronary Calcium Score Software Empowered by Artificial Intelligence Technology Validation Study Using Three CT Cohorts

Objective: This study aimed to validate a deep learning-based fully automatic calcium scoring (coronary artery calcium [CAC]_auto) system using previously published cardiac computed tomography (CT) cohort data with the manually segmented coronary calcium scoring (CAC_hand) system as the reference standard. Materials and Methods: We developed the CAC_auto system using 100 co-registered, non-enhanced and contrast-enhanced CT scans. For the validation of the CAC_auto system, three previously published CT cohorts (n = 2985) were chosen to represent different clinical scenarios (i.e., 2647 asymptomatic, 220 symptomatic, 118 valve disease) and four CT models. The performance of the CAC_auto system in detecting coronary calcium was determined. The reliability of the system in measuring the Agatston score as compared with CAC_hand was also evaluated per vessel and per patient using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. The agreement between CAC_auto and CAC_hand based on the cardiovascular risk stratification categories (Agatston score: 0, 1-10, 11-100, 101-400, &gt; 400) was evaluated. Results: In 2985 patients, 6218 coronary calcium lesions were identified using CAC_hand. The per-lesion sensitivity and false positive rate of the CAC_auto system in detecting coronary calcium were 93.3% (5800 of 6218) and 0.11 false-positive lesions per patient, respectively. The CAC_auto system, in measuring the Agatston score, yielded ICCs of 0.99 for all the vessels (left main 0.91, left anterior descending 0.99, left circumflex 0.96, right coronary 0.99). The limits of agreement between CAC_auto and CAC_hand were 1.6 +/- 52.2. The linearly weighted kappa value for the Agatston score categorization was 0.94. The main causes of false-positive results were image noise (29.1%, 97/333 lesions), aortic wall calcification (25.5%, 85/333 lesions), and pericardial calcification (24.3%, 81/333 lesions). Conclusion: The atlas-based CAC_auto empowered by deep learning provided accurate calcium score measurement as compared with manual method and risk category classification, which could potentially streamline CAC imaging workflows