프로젝트 번호 NVKP_16-1–2016-0017 ( 'National Heart Program')은 NVKP_16 기금 계획에 따라 자금을 조달 한 헝가리 국립 연구, 개발 및 혁신 기금의 지원으로 시행되었습니다. 이 연구는 Semmelweis University의 치료 개발 및 바이오이미징 주제 프로그램의 틀 내에서 헝가리 혁신 기술부의 주제별 우수 프로그램(2020-4.1.1.-TKP2020)의 재정 지원을 받았습니다.

이 프로토콜은 기관의 인간 연구 윤리위원회의 지침을 따르며 임상 사례의 환자는 연구에 대한 서면 동의를했습니다.
1. 기술 요구 사항
<ol><li>3D 수집 및 분석을 위해서는 적절한 소프트웨어와 하드웨어를 사용하십시오. 심 초음파 장치의 ECG 케이블을 사용하십시오. 또한 아래에 설명된 완전한 3D 획득 프로토콜에 필수입니다.</li>
	<li>3D 획득의 경우 3D 심 초음파 프로브와 3D 호환 초음파 기계를 사용하십시오. 3D RV 체적 해석의 경우 전용 소프트웨어를 사용하십시오.</li>
</ol>2. 인수
<ol><li>대부분의 경우 정점 뷰를 사용하여 RV의 3D 획득을 수행합니다. LV 중심의 견해와는 달리, 다른 환자 위치가 권장됩니다. 만약 실질적으로 더 나은 이미지 품질이 정확한 정점 뷰 위에 하나의 늑간 공간으로 전환함으로써 달성될 수 있다면, 이러한 단축된 뷰는 더 나은 3D 이미지 품질을 가능하게 할 수 있다. 단축법은 3D 해석 중에 수정할 수 있습니다.<ol><li>왼쪽 측면 욕창 위치 (환자가 머리 위로 뻗은 상태에서 왼쪽에 누워있는 환자)가 권장되는 표준 정점 심 초음파 획득과 비교하여 환자를 약간 더 뒤로 기울여 변환기의 측면 위치를 가능하게합니다.</li>
		<li>RV만 포함하는 이미지 깊이를 선택합니다. 불필요하게 큰 깊이는 RV 체적 분석과 관련하여 유익한 효과가 부족하여 획득 프레임 속도를 낮출 수 있습니다.</li>
	</ol></li>
	<li>2D 심 초음파 이미지에서 올바른 RV 초점 보기를 확인합니다. RV의 자유 벽이이보기에서도 제대로 시각화되지 않으면 예상되는 3D 이미지 품질이 추가 분석에 최적이 아닙니다.</li>
	<li>RV 보기의 추가 보정을 수행할 수 있는 4D 버튼을 사용하여 라이브 3D 이미징으로 전환합니다.</li>
	<li>3D 라이브 모드는 미학적으로 매우 만족스러울 수 있지만 관심 영역의 삼중 평면 이미지와 자유롭게 수정할 수 있는 9개의 단면 평면을 보여주는 3D 보기에 12 슬라이스 모드를 사용합니다. 절단면의 회전 및 올바른 위치를 통해 전체 RV 자유 벽(유출로 및 정점 세그먼트 포함)의 가시성을 확인합니다.</li>
	<li>섹터의 왼쪽 기울기(터치 스크린의 두 번째 페이지)를 사용하여 이미지를 추가로 조정하여 RV 시각화를 개선합니다.</li>
	<li>RV 체적 분석을 위해 두 가지 3D 획득 모드( 멀티 비트 및 단일 비트 모드)를 사용합니다. 모든 환자에서 이 두 가지 접근법을 모두 사용하지만 일부 경우(예: 특정 부정맥, 환자의 심한 호흡곤란)에는 후자만 가능할 수 있습니다.</li>
	<li>단일 비트 모드를 사용하면 이미지 품질과 프레임 속도 간의 균형을 유지할 수 있습니다. 최적의 이미지 깊이, 너비 및 프레임 속도(터치 스크린의 하단 패널)를 선택하고 추가 작업 없이 RV의 3D 루프를 얻습니다. 이 방법은 대다수의 환자에서 가능합니다. 그러나 일반적으로 다중 비트 접근 방식에 비해 이미지 품질과 프레임 속도가 낮습니다.<ol><li>평균(60-70/분) 심박수의 경우 적절한 RV 분석을 위해 16프레임/초의 낮은 프레임 속도 제한을 유지하십시오. 그러나 빈맥이 있는 경우 더 높은 프레임 속도가 권장됩니다.</li>
	</ol></li>
	<li>멀티 비트 모드를 사용하여 터치 스크린에서 선택할 수있는 주어진 수의 심박수 사이클에서 획득 한 3D 루프를 재구성합니다 (2,3,4 및 6 비트 모드를 사용할 수 있음). 단일 비트 획득과 달리 일반적으로 더 나은 이미지 품질과 프레임 속도가 예상됩니다. 그러나 비교적 일정한 심장 주기 길이와 의무적인 호흡 참기 기동으로 인한 환자 순응도가 필요합니다. 이 조작은 소위 스티칭 아티팩트를 피하기 위해 필수적입니다 : 획득 된 3D 볼륨을 함께 스티칭 할 때 호흡으로 인한 심장 사이클 길이 및 / 또는 움직임이 동일하지 않으면 이러한 현상이 발생할 수 있습니다.<ol><li>프로브의 올바른 위치와 기계 설정 후("단일 비트" 모드와 유사) 환자에게 심호흡을 하고 참도록 요청하십시오. 이 경우 팽창하는 폐는 일반적으로 전체 이미지를 덮습니다.</li>
		<li>환자에게 천천히 숨을 내쉬도록 요청하십시오. 폐의 수축과 병행하여 RV가 다시 보입니다.</li>
		<li>전체 RV (자유 벽 및 중격)가 다시 나타나면 환자에게이 상태에서 숨을 참도록 요청하십시오.</li>
		<li>화면에서 멀티 비트 를 클릭하여 획득을 시작하면 주어진 양의 심장 주기 동안 3D 루프가 구축됩니다.</li>
		<li>획득이 준비되면(전체 RV가 시각화됨) 환자에게 다시 자유롭게 호흡하도록 요청하십시오.</li>
		<li>가져온 루프를 검사하여 스티칭 또는 드롭아웃 아티팩트가 없는지 확인합니다.</li>
	</ol></li>
</ol>3. 4D RV 분석
<ol><li>전용 소프트웨어를 사용하여 RV의 3D 체적 분석을 수행합니다. 환자 라이브러리에서 RV 중심 3D 루프를 선택한 후 볼륨 폴더에 있는 측정 창에서 소프트웨어를 엽니다.</li>
	<li>소프트웨어를 연 후 미리 정의된 4개의 절단 평면에서 RV의 방향을 지정합니다.<ol><li>두 개의 마커 (TV Center)를 왼쪽 상단 및 하단 장축 평면의 삼첨판 중심에 놓습니다. 회전 도구를 사용하여 이미지의 장축을 RV의 실제 장축으로 조정합니다. 오른쪽 위 가장자리의 참조 이미지는 올바른 방향이 어떻게 나타나야 하는지 보여줍니다.</li>
		<li>오른쪽 위 및 아래 패널에서 회전하여 단축 이미지를 올바른 위치에 맞춥니다. 이전 단계와 마찬가지로 참조 이미지도 이 프로세스에 도움이 됩니다.</li>
	</ol></li>
	<li>작업을 마친 후 랜드마크를 분석의 다음 단계로 설정을 클릭합니다. 두 개의 이미지로 랜드마크를 설정합니다.<ol><li>왼쪽에는 자유 벽 (TV 자유 벽)과 격막 (TV 중격)의 삼첨판 고리와 RV 정점을 이전에 지향 된 정점 4 챔버보기에 표시하십시오.</li>
		<li>오른쪽에서 RV 후방(LV/RV 후방) 및 전방 삽입 지점(LV/RV 전방)과 RV 자유 벽(RV 자유 벽)을 설정합니다. 이전 창과 마찬가지로 오른쪽 상단 모서리에 있는 참조 이미지는 올바른 설정에 대해 도움이 됩니다. 모든 랜드 마크를 설정하면 소프트웨어가 자동으로 다음 창으로 이동합니다 (검토).</li>
	</ol></li>
	<li>이 창(Review)에서, 필요한 경우, 전체 심장 주기에 걸쳐 자동 심내막 경계 검출을 검토하고 수동으로 수정한다. 기본적으로 9 개의 패널을 볼 수 있습니다 : 왼쪽에는 3 개의 움직이는 루프 (1 개의 장축 및 2 개의 단축), 중간에는 동일한 이미지의 이완기 말단 프레임, 오른쪽에는 수축기 말단 프레임이 있습니다.<ol><li>잘못된 추적의 경우, 심내막 경계 (녹색 선), 추적 된 경계를 클릭하여 자유롭게 수정하십시오. 짧은 축의 회전 도구를 사용하여 RV의 전체 둘레를 따라 추적되는 이미지를 검토합니다. 오른쪽 패널에서 펜 크기를 선택하여 수정 크기를 조정합니다. 추적이 올바른 것으로 간주되면 동일한 패널에서 결과를 클릭합니다.</li>
	</ol></li>
	<li>마지막 섹션에서는 오른쪽 상단(워크시트 패널)에서 최종 3D 체적 데이터 및 기타 계산된 매개변수를 검토합니다. RV 부피 및 배출 분율 외에도 소프트웨어는 선형(중간, 기저 및 장축) 직경과 같은 2D 매개변수와 사전 정의된 정점 4개 챔버 보기에서 파생된 FAC 및 TAPSE 값도 표시합니다. 이 소프트웨어는 또한 RV의 길고 짧은 축(왼쪽), RV의 3D 라이브 모델(상단 중앙) 및 챔버의 체적 시간 곡선(오른쪽 하단)을 보여줍니다.<ol><li>추적을 추가로 조정해야하는 경우 오른쪽 패널에서 이전 단계를 클릭하여 수정할 수 있습니다. 추적 및 3D 매개변수가 유효한 것으로 간주되면 동일한 패널에서 "승인 및 종료"를 클릭하여 결과를 저장합니다.</li>
	</ol></li>
</ol>

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K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dominance+of+free+wall+radial+motion+in+global+right+ventricular+function+of+heart+transplant+recipients.">Dominance of free wall radial motion in global right ventricular function of heart transplant recipients.</a> Clinical Transplantation. 32 (3), e13192 (2018).</li><li>Raina, A., Vaidya, A., Gertz, Z. M., Susan, C., Forfia, P. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Marked+changes+in+right+ventricular+contractile+pattern+after+cardiothoracic+surgery:+implications+for+post-surgical+assessment+of+right+ventricular+function.">Marked changes in right ventricular contractile pattern after cardiothoracic surgery: implications for post-surgical assessment of right ventricular function.</a> Journal of Heart and Lung Transplantation. 32 (8), 777-783 (2013).</li><li>Nowak-Machen, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+Right+Ventricular+Volume+and+Function+Analysis+Using+Intraoperative+3-Dimensional+Echocardiography-Derived+Mesh+Models.">Regional Right Ventricular Volume and Function Analysis Using Intraoperative 3-Dimensional Echocardiography-Derived Mesh Models.</a> Journal of Cardiothoracic and Vascular Anesthesia. 33 (6), 1527-1532 (2019).</li><li>Pettersen, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contraction+pattern+of+the+systemic+right+ventricle+shift+from+longitudinal+to+circumferential+shortening+and+absent+global+ventricular+torsion.">Contraction pattern of the systemic right ventricle shift from longitudinal to circumferential shortening and absent global ventricular torsion.</a> Journal of the American College of Cardiology. 49 (25), 2450-2456 (2007).</li><li>Moceri, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+right-ventricular+regional+deformation+and+survival+in+pulmonary+hypertension.">Three-dimensional right-ventricular regional deformation and survival in pulmonary hypertension.</a> European Heart Journal - Cardiovascular Imaging. , (2017).</li><li>Addetia, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+echocardiography-based+analysis+of+right+ventricular+shape+in+pulmonary+arterial+hypertension.">Three-dimensional echocardiography-based analysis of right ventricular shape in pulmonary arterial hypertension.</a> European Heart Journal - Cardiovascular Imaging. 17 (5), 564-575 (2016).</li><li>Addetia, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphologic+Analysis+of+the+Normal+Right+Ventricle+Using+Three-Dimensional+Echocardiography-Derived+Curvature+Indices.">Morphologic Analysis of the Normal Right Ventricle Using Three-Dimensional Echocardiography-Derived Curvature Indices.</a> Journal of the American Society of Echocardiography. 31 (5), 614-623 (2018).</li><li>Lakatos, B. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise-induced+shift+in+right+ventricular+contraction+pattern:+novel+marker+of+athlete's+heart?.">Exercise-induced shift in right ventricular contraction pattern: novel marker of athlete's heart?.</a> American Journal of Physiology - Heart and Circulatory. , (2018).</li><li>Corrado, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arrhythmogenic+right+ventricular+cardiomyopathy:+evaluation+of+the+current+diagnostic+criteria+and+differential+diagnosis.">Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis.</a> European Heart Journal. , (2019).</li><li>Luo, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Right+ventricular+outflow+tract+systolic+function+correlates+with+exercise+capacity+in+patients+with+severe+right+ventricle+dilatation+after+repair+of+tetralogy+of+Fallot.">Right ventricular outflow tract systolic function correlates with exercise capacity in patients with severe right ventricle dilatation after repair of tetralogy of Fallot.</a> Interactive Cardiovascular and Thoracic Surgery. 24 (5), 755-761 (2017).</li></ol>

RV의 3D 분석은 일상적인 심장학 실습에서 중요한 단계입니다. 이전에 무시되었던 심장실의 형태와 기능에 대한 관심이 증가함에 따라 이러한 새로운 솔루션은 심장의 오른쪽에 대한 임상적으로 의미 있는 정보를 제공합니다. 3D 획득은 2D 심 초음파 영상과 현저하게 다른 몇 가지 측면을 가지고 있지만, 임계점에 특별한주의를 기울이고 철저한 프로토콜을 사용함으로써 3D RV 분석은 과학적 도구에?...

심 초음파는 1950 년대 첫 임상 적용에서 먼 길을 왔습니다1. 최초의 1차원 초음파 프로브는 챔버 벽과 루멘의 단순한 선형 직경을 제공하도록 설계되었습니다. 그러나 의심 할 여지없이 심혈관 영상의 이정표를 나타냅니다. 2차원(2D) 초음파 영상의 개발은 형태와 기능의 훨씬 더 정확한 정량화를 제공함으로써 또 다른 주요 단계였으며 여전히 일상적인 임상 실습에서 표준 방법으로 간주됩니다. 그럼에도 불구하고, 2D 심 초음파 기반 평가는 여전히이 기술의 주요 한계를 가지고 있습니다 : 몇 개의 단층 촬영 평면에서 주어진 챔버의 이미징은 3 차원 (3D) 구조의 형태와 기능을 적절하게 특성화하지 못합니다. 이 문제는 우심실 (RV)의 경우에 더욱 두드러진다 : 비교적 단순한 총알 모양의 좌심실 (LV)과 비교하여, RV는 선형 직경 또는 영역3을 사용하여 적절하게 정량화 될 수없는 복잡한 기하학(2)을 갖는다. 이러한 널리 알려진 사실에도 불구하고, RV 형태 및 기능은 일반적으로 임상 실습에서 이러한 간단한 파라미터에 의해 측정된다.
수십 년 동안 RV는 왼쪽 대응 물에 비해 순환에서 훨씬 덜 중요한 역할을하는 것으로 간주되었습니다. 여러 획기적인 논문은 다양한 질병 4,5,6,7에서 RV 기하학과 기능의 강력한 예후 역할을 보여주는 이러한 관점을 무효화했습니다. 수많은 연구에서 비교적 간단한 기존 파라미터를 사용하더라도 RV 측정의 증분 가치를 입증했으며, 이는 잠재적으로 의미 있는 임상적 가치를 가진 챔버의 보다 정확한 정량화의 중요성과 필요성을 강조합니다.
3D 심 초음파는 심장 챔버의 2D 평가의 몇 가지 한계를 극복합니다. LV의 경우에도 부피 및 기하학적 가정이없는 기능 매개 변수의 측정이 높은 관심을 끌 수 있지만 RV8의 평가에서 특히 중요 할 수 있습니다. 3D 유래 RV 부피 및 박출률(EF)은 다양한 심혈관 질환에서 유의한 예후 값을 갖는 것으로 나타났다9,10.
오늘날 여러 공급업체는 금 표준 심장 자기 공명(MR) 측정(11,12)에 대해 검증된 결과를 제공하는 3D RV 평가를 위한 반자동 솔루션을 제공합니다. 3D 평가의 기술적 요구 사항은 오늘날 최첨단 심혈관 영상 부서의 필수적인 부분이며 곧 모든 심 초음파 실험실의 일반 장비의 일부가 될 것으로 예상됩니다. 3D 획득 및 후처리에 대한 적절한 전문 지식을 갖춘 3D RV 분석을 표준 검사 프로토콜에 쉽게 구현할 수 있습니다.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3V-D/4V-D/4Vc-D</td>
			<td>General Electric</td>
			<td>n.a.</td>
			<td>ultrasound probe</td>
		</tr>
		<tr>
			<td>4D Auto RVQ</td>
			<td>General Electric</td>
			<td>n.a.</td>
			<td>software for analysis</td>
		</tr>
		<tr>
			<td>E9/E95</td>
			<td>General Electric</td>
			<td>n.a.</td>
			<td>ultrasound machine</td>
		</tr>
		<tr>
			<td>EchoPac v203</td>
			<td>General Electric</td>
			<td>n.a.</td>
			<td>software for analysis</td>
		</tr>
	</tbody>
</table>

morphological and functional assessment of the right ventricle using 3d echocardiography

전통적으로 심장의 오른쪽은 순환에 작은 역할을한다고 믿어졌습니다. 그러나 점점 더 많은 데이터가 우심실 (RV) 기능이 다양한 심혈관 질환에서 강력한 진단 및 예후력을 가지고 있음을 시사합니다. 복잡한 형태와 기능으로 인해 기존의 2 차원 심 초음파에 의한 RV 평가는 제한적입니다 : 일상적인 임상 실습은 일반적으로 단순한 선형 치수 및 기능적 측정에 의존합니다. 3차원(3D) 심초음파는 기하학적 가정 없이 RV의 체적 정량화를 제공함으로써 이러한 한계를 극복했습니다. 여기에서는 상업적으로 이용 가능한 선도적 인 소프트웨어를 사용하여 RV의 3D 심 초음파 데이터를 얻고 분석하는 단계별 가이드를 제공합니다. 3D RV 부피와 배출 비율을 정량화합니다. 몇 가지 기술적 측면이 RV 획득 및 분석의 품질을 개선하는 데 도움이 될 수 있으며, 이는 실용적인 방식으로 제시합니다. 우리는 이 방법의 현재 기회와 제한 요소를 검토하고 현재 임상 실습에서 3D RV 평가의 잠재적인 적용을 강조합니다.

RV의 3D 분석은 다양한 심혈관 질환에서 가능합니다. 사례 1은 정상적인 심실 부피와 기능을 가진 건강한 지원자입니다 (그림 1). 사례 2는 종래의 2D 평가의 상충되는 결과에 대한 전형적인 예인 승모판 후 복구된 환자이다: TAPSE가 현저하게 감소된 반면, 환자는 RV 기능장애의 어떠한 징후도 나타내지 않고 RV 글로벌 수축기 기능이 정상 3D RV EF에 의해 확...

Watch this Scientific Journal Video about Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography at JoVE.com

Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography

여기에서는 우심실의 3D 체적 평가를 위한 단계별 획득 및 분석 프로토콜을 제공하며, 주로 이 기술의 실현 가능성을 극대화하는 실용적인 측면에 중점을 둡니다.

3D 심 초음파를 사용한 우심실의 형태 학적 및 기능적 평가

Traditionally, it was believed that the right side of the heart has a minor role in circulation; however, more and more data suggest that right ...

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2.7K 조회수.  Semmelweis University Heart and Vascular Center. 여기에서는 우심실의 3D 체적 평가를 위한 단계별 획득 및 분석 프로토콜을 제공하며, 주로 이 기술의 실현 가능성을 극대화하는 실용적인 측면에 중점을 둡니다.

비디오: Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography

Transthoracic Echocardiography in Mice

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene expression. Transgenic and gene targeting methods can be used to generate mice with altered cardiac size and function,1-3 and as a result, in vivo techniques are needed to evaluate their cardiac phenotype. Transthoracic echocardiography, pulse wave Doppler (PWD), and tissue Doppler imaging (TDI) can be used to provide dimensional measurements of the mouse heart and to quantify the degree of cardiac systolic and diastolic performance. Two-dimensional imaging is used to detect abnormal anatomy or movements of the left ventricle, whereas M-mode echo is used for quantification of cardiac dimensions and contractility.4,5 In addition, PWD is used to quantify localized velocity of turbulent flow,6 whereas TDI is used to measure the velocity of myocardial motion.7 Thus, transthoracic echocardiography offers a comprehensive method for the noninvasive evaluation of cardiac function in mice.

Transthoracic echocardiography offers a noninvasive method for the evaluation of cardiac function in mice. A combination of ultrasound and Doppler imaging modalities can be used to obtain dimensional measurements of the heart and intracardiac blood flow, which together provide an assessment of cardiac systolic and diastolic performance.

마우스에 Transthoracic Echocardiography

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene ...

연구

의학

Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice. Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

마우스의 오른쪽 심장의 심 초음파 평가

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, the RV is significantly affected in pulmonary diseases such as pulmonary artery hypertension (PAH). In addition, the RV is remarkably sensitive to cardiac pathologies, including left ventricular (LV) dysfunction, valvular disease or RV infarction4. To understand the role of RV in the pathogenesis of cardiac diseases, a reliable and noninvasive method to access the RV structurally and functionally is essential.
A noninvasive trans-thoracic echocardiography (TTE) based methodology was established and validated for monitoring dynamic changes in RV structure and function in adult mice. To impose RV stress, we employed a surgical model of pulmonary artery constriction (PAC) and measured the RV response over a 7-day period using a high-frequency ultrasound microimaging system. Sham operated mice were used as controls. Images were acquired in lightly anesthetized mice at baseline (before surgery), day 0 (immediately post-surgery), day 3, and day 7 (post-surgery). Data was analyzed offline using software.
Several acoustic windows (B, M, and Color Doppler modes), which can be consistently obtained in mice, allowed for reliable and reproducible measurement of RV structure (including RV wall thickness, end-diastolic&#160;and end-systolic dimensions), and function (fractional area change, fractional shortening, PA peak velocity, and peak pressure gradient) in normal mice and following PAC.
Using this method, the pressure-gradient resulting from PAC was accurately measured in real-time using Color Doppler mode and was comparable to direct pressure measurements performed with a Millar high-fidelity microtip catheter. Taken together, these data demonstrate that RV measurements obtained from various complimentary views using echocardiography are reliable, reproducible and can provide insights regarding RV structure and function. This method will enable a better understanding of the role of RV cardiac dysfunction.

Right ventricle (RV) dysfunction is critical to the pathogenesis of cardiovascular disease, yet limited methodologies are available for its evaluation. Recent advances in ultrasound imaging provide a noninvasive and accurate option for longitudinal RV study. Herein, we detail a step-by-step echocardiographic method using a murine model of RV pressure overload.

경 흉부 심 초음파에 의한 폐동맥 수축의 마우스 모델에서 마우스 오른쪽 심실 구조 및 기능의 평가

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

돼지의 심근 경색 및 기능적 결과의 평가

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

만성 혈전 색 전성 폐 고혈압과 돼지에서 마우스 오른쪽 심실 기능의 평가

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function2. Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

The goal of this protocol is to noninvasively assess cardiac structural and functional changes in a mouse model of heart disease created by transverse aortic constriction, using B- and M-mode echocardiography and color/pulse wave Doppler imaging.

심 초음파 이미징에 의해 가로 대동맥 수축의 마우스 모델에서 심장 형태 학적 평가 및 기능 변경

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

Transthoracic Speckle Tracking Echocardiography for the Quantitative Assessment of Left Ventricular Myocardial Deformation

The value of conventional echocardiography is limited by differences in inter-individual image interpretation and therefore largely dependent on the examiners&#39; expertise. Speckle tracking Echocardiography (STE) is a promising but technically challenging method that can be used to quantitatively assess regional and global systolic and diastolic myocardial performance. Myocardial strain and strain rate can be measured in all three dimensions&#160;&#8212; radial, circumferential, longitudinal &#8212; of myocardial deformation. Standard cross-sectional two-dimensional B-mode images are recorded and subsequently postprocessed by automated continuous frame-by-frame tracking and motion analysis of speckles within the myocardium. Images are recorded as digital loops and synchronized to a 3-lead EKG for timing purposes. Longitudinal deformation is assessed in the apical 4-, 3-, and 2-chamber views. Circumferential and radial deformation are measured in the parasternal short axis plane.
Optimal image quality and accurate tissue tracking are paramount for the correct determination of myocardial performance parameters. Utilizing transthoracic STE in a healthy volunteer, the present article is a detailed outline of the essential steps and potential pitfalls of quantitative echocardiographic myocardial deformation analysis.

Speckle tracking echocardiography is an emerging diagnostic imaging technique for the quantitative assessment of global and regional myocardial performance. Standard view echocardiographic motion images are recorded and deformation parameters are subsequently measured by automated continuous frame-by-frame tracking and motion analysis of speckles within the B-mode images of the myocardium.

좌심실 심근 변형의 정량적 평가를위한 흉부 얼룩 추적 심 초음파

The value of conventional echocardiography is limited by differences in inter-individual image interpretation and therefore largely dependent on the ...

Assessment of the Anticoagulant and Anti-inflammatory Properties of Endothelial Cells Using 3D Cell Culture and Non-anticoagulated Whole Blood

In vivo, endothelial cells are crucial for the natural anticoagulation of circulating blood. Consequently, endothelial cell activation leads to blood coagulation. This phenomenon is observed in many clinical situations, like organ transplantation in the presence of pre-formed anti-donor antibodies, including xenotransplantation, as well as in ischemia/reperfusion injury. In order to reduce animal experimentation according to the 3R standards (reduction, replacement and refinement), in vitro models to study the effect of endothelial cell activation on blood coagulation would be highly desirable. However, common flatbed systems of endothelial cell culture provide a surface-to-volume ratio of 1 - 5 cm2 of endothelium per mL of blood, which is not sufficient for natural, endothelial-mediated anticoagulation. Culturing endothelial cells on microcarrier beads may increase the surface-to-volume ratio to 40 - 160 cm2/mL. This increased ratio is sufficient to ensure the &#34;natural&#34; anticoagulation of whole blood, so that the use of anticoagulants can be avoided. Here an in vitro microcarrier-based system is described to study the effects of genetic modification of porcine endothelial cells on coagulation of whole, non-anticoagulated human blood. In the described assay, primary porcine aortic endothelial cells, either wild type (WT) or transgenic for human CD46 and thrombomodulin, were grown on microcarrier beads and then exposed to freshly drawn non-anticoagulated human blood. This model allows for the measurement and quantification of cytokine release as well as activation markers of complement and coagulation in the blood plasma. In addition, imaging of activated endothelial cell and deposition of immunoglobulins, complement- and coagulation proteins on the endothelialized beads were performed by confocal microscopy. This assay can also be used to test drugs which are supposed to prevent endothelial cell activation and, thus, coagulation. On top of its potential to reduce the number of animals used for such investigations, the described assay is easy to perform and consistently reproducible.

We present an in vitro model which allows the study and analysis of coagulation in whole, non-anticoagulated blood. Anticoagulation in the system depends on the natural anticoagulation effect of healthy endothelial cells and endothelial cell activation will result in clotting.

3D 세포 배양 및 비 anticoagulated 전 혈을 사용 하 여 내 피 세포의 항 응 혈 약 그리고 항 염증 제 속성에 대 한 평가

In vivo, endothelial cells are crucial for the natural anticoagulation of circulating blood. Consequently, endothelial cell activation leads to blood ...

2D and 3D Echocardiography in the Axolotl (Ambystoma Mexicanum)

Cardiac malfunction as a result of ischemic heart disease is a major challenge, and regenerative therapies to the heart are in high demand. A few model species such as zebrafish and salamanders that are capable of intrinsic heart regeneration hold promise for future regenerative therapies for human patients. To evaluate the outcome of cardioregenerative experiments it is imperative that heart function can be monitored. The axolotl salamander (A. mexicanum) represents a well-established model species in regenerative biology attaining sizes that allows for evaluation of cardiac function. The purpose of this protocol is to establish methods to reproducibly measure cardiac function in the axolotl using echocardiography. The application of different anesthetics (benzocaine, MS-222, and propofol) is demonstrated, and the acquisition of two-dimensional (2D) echocardiographic data in both anesthetized and unanesthetized axolotls is described. 2D echocardiography of the three-dimensional (3D) heart can suffer from imprecision and subjectivity of measurements, and to alleviate this phenomenon a solid method, namely intra/inter-operator/observer analysis, to measure and minimize this bias is demonstrated. Finally, a method to acquire 3D echocardiographic data of the beating axolotl heart at a very high spatiotemporal resolution and with pronounced blood-to-tissue contrast is described. Overall, this protocol should provide the necessary methods to evaluate cardiac function and model anatomy, and flow dynamics in the axolotl using ultrasound imaging with applications in both regenerative biology and general physiological experiments.

2D and 3D Echocardiography in the Axolotl Ambystoma Mexicanum

Here we present echocardiography protocols for two-dimensional and three-dimensional image acquisition of the beating heart of the axolotl salamander (Ambystoma mexicanum), a model species in heart regeneration. These methods allow for longitudinal evaluation of cardiac function at a high spatiotemporal resolution.

Axolotl (Ambystoma Mexicanum)에서 2 차원 및 3 차원 심장 초음파 검사

Cardiac malfunction as a result of ischemic heart disease is a major challenge, and regenerative therapies to the heart are in high demand. A few model ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

마우스에 있는 우심실 시스템 및 저산소증 유도된 폐 동맥 고혈압을 위한 침략적인 혈역학 평가

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...