This work was supported by the National Institutes of Health (HL114669). CM is a recipient of a postdoctoral research fellowship grant awarded by the Myocarditis Foundation, NJ.

윤리 선언문 : 모든 동물의 절차는 실험 동물의 관리 및 사용에 대한 지침에 따라 실시 및 네브래스카 링컨, 링컨, 네브래스카의 대학에 의해 승인되었습니다. 실험자가 면역 심근염 1. 유도 <ol><li> 이 mg/1.5 ml의 최종 농도 1X 인산 완충 식염수에 Myhc-α 334-352 용해시켜 펩티드 용액을 준비한다. </li><li> 50 NG / μL의 스톡 농도를 구하는 동결 건조 PT 50 μg을 함유하는 바이알에 무균 1X PBS 1 ㎖를 첨가하여, 백일해 독소 (PT)을 준비한다. 멸균 1.5 ML 튜브에 주식의 20 μl를 타고 1 NG / μL의 작업 농도를 얻기 위해 멸균 1X PBS 980 μl를 추가합니다. </li><li> 결핵균 H37Rv 40 밀리그램을 추가하여 완전한 프로 인트 보조제 (CFA)를 준비 (MTB)의 최종 농도를 얻기 위해 CFA 10 ㎖로 추출5 ㎎ / ㎖. </li><li> 펩티드-CFA 에멀젼을 준비합니다. 참고 : EAM 유도를 들어, 펩티드 CFA 에멀젼 Myhc-α 동물 당 334-352의 100 μg을 함유하는 150 ㎕를 투여했다. 예를 들어, 열 마우스 Myhc-α 334-352 1 ㎎을 함유하는 펩티드-CFA 에멀젼의 1.5 ML를 사용하여 면역합니다. <ol><li> 에멀젼의 1.5 ML를 준비하려면, 나누어지는 750 개의 1.5 ML 튜브에 334-352 펩타이드 솔루션을 Myhc가-α의 μL 및 CFA는 또 다른 1.5 ML 튜브에 MTB 보충. 3 ㎖의 루어-LOK 주사기를 사용하여, CFA / MTB 엑기스이어서 제 펩티드 용액을 그린다. </li><li> 3 방향 꼭지에 주사기를 연결하고 빈 3 ML의 주사기에 꼭지의 다른 콘센트에 연결합니다. 그래서 펩타이드 CFA 혼합물을 합리적으로 좋은 저항과 다른 하나의 주사기에서 흘러 크레인의 개통을 조정합니다. </li><li> ~ 1 분 동안 반복하여 다른 하나의 주사기에서 내용을 추진 한 다음 2 ~ 3 분 동안 얼음에 전체 어셈블리를 배치하여 혼합. 이 과정을 반복합니다10 배의 절차에 최소. </li><li> 주의 깊게 100 ㎖ 유리 비커에 아직도 물에 작은 방울을 배치하여 에멀젼의 일관성을 확인합니다. 방울은 물에 분산 할 것으로 예상되지 않습니다. 만약 그렇다면, 원하는 농도가 달성 될 때까지 계속 혼합한다. </li><li> 1 mL의 주사기와 마개에 부착 된 두 개의 3-ML 주사기 중 하나를 교체하여 1 ㎖ 루어 코리아 주사기로 3 ㎖ 주사기에서 에멀젼의 내용을 전송하고 1 ML의 주사기에 27 ½ G 바늘을 연결합니다. </li></ol></li><li> 6 년에서 8 주 된 여성 A / J 마우스 (~ 75 μL 각)의 두 사타구니 지역에 분할 복용 피하에있는 펩티드-CFA 에멀젼 150 μl를 주입한다. </li><li> 0 일 및 2 일 postimmunization에 복강 내 각 동물에 PT 서스펜션 (100 NG)의 100 μl를 관리 할 수​​ 있습니다. </li><li> 피하 t의 양쪽에 분할 복용 펩타이드 CFA 에멀젼 150 μl를 투여하여 7 일째에 예방 접종 절차를 반복그는 흉골 (~ 75 μL 각). 신선한 등의 이상이 에멀젼을 준비합니다. 그 후, 21 일에, MRM 영상에 동물을 대상 3 단계를 참조하십시오. </li></ol> 2. 동물 취급 <ol><li> 따뜻함을 유지하기 위해 아래에 배치 된 가열 패드 2 % 이소 플루 란 - 공기 혼합물을 포함하는 마취 유도 챔버 각 마우스를 배치하고 특별히 디자인 된 동물 홀더 (그림 1)에 동물을 전송합니다. </li><li> 동물 홀더에 발생하기 쉬운 위치에 동물을 무력화 그래서 주둥이는 마취 (그림 1)를 유지하기 위해 코 콘에 맞는. 마우스의 앞니에 부착 된 물린 바로 마우스의 머리를 고정합니다. </li><li> 실험 기간 동안 동물의 체온을 유지하기 위해 스캐너의 수직 구멍에 삽입의 출구 호스에 공기를 불어 히터의 전원을 켭니다. </li><li> 촬상 전체 세션 동안 2 ㎖ / 분의 유속으로 0.5 내지 2 %의 이소 플루 란으로 마취를 유지한다. 확인발가락 핀치 방법을 사용하여 마취, 아무 움직임이 예상. </li><li> 압축 공기를 넣은 베개 센서, 마우스 꼬리 / 발목 광섬유 맥박 산소 센서, 각각 호흡, 심장 박동과 체온, (그림 1)를 모니터링하는 직장 온도 프로브를 설정합니다. 참고 : 심장 게이팅이 동맥혈 산소 포화도의 비 침습적 모니터링을 허용 맥박 산소 측정기를 통해 수행된다. 산소 포화도 센서는 좌측 발목에 부착되어야하고, 다리 실 루프로 고정하고 센서의 발목을 유지하기 위해 녹화한다. MRM 촬상 어떤 조영제를 사용하지 않고 호흡과 심장 신호를 게이팅함으로써 달성된다. </li></ol> 3. 이미지 획득 <ol><li> 동물 (도 1)를 제조 한 후, 자기장의 균질성이 최대가 시야 (FOV)의 중앙에 위치 마음 MRM 스캐너의 중심에 마우스를 배치. 참고 : 와이드 보어(89mm) 트리플 100 G / cm의 축 그라디언트 및 4cm의 무선 주파수 (RF) 촬상 코일 탑재 9.4 T 수직 보어 자석 고해상도 3 차원 (3D) 이미지를 얻기 위해 사용한다. 주 : MRI 스캐너를 사용하는 경우 비자로 제공해야합니다. </li><li> 영상 인터페이스를 실행하고 &quot;연구 옵션&quot;메뉴에서 &quot;새로운 연구&quot;를 선택합니다. 명령 줄에서 &quot;mtune&quot;를 입력하고 &quot;조정 GUI&quot;를 끌어 실행합니다. &quot;시작 프로브 조정&quot;을 선택하고 &quot;자동 스케일&quot;버튼을 클릭합니다. 조정 GUI는 RFsignal를 표시하도록 변경됩니다. 튜닝 프로톤 공명 주파수 RF 코​​일 (400 MHz 이상)에서 코일의 단부에서 원격 튜닝 / 매치 노브를 사용. &quot;시작&quot;탭에서 관련 버튼을 클릭하여 주파수 및 전력 보정을 실행하려면 &quot;설치 전&quot;페이지로 이동합니다. shimming 페이지를 끌어 탭 &#39;연구 심 &quot;탭&quot;&#39;에 XYZ (빠른) 버튼을 누르십시오., 심 페이지로 이동 모든 반복을 선택하고 자동 shimming을 수행하기 위해 심 버튼을 누르십시오. </li><li> 마우스 마음을 집중하는 영상 인터페이스의 &quot;연구&quot;탭에서 스카우트 순서를 선택합니다. &quot;획득&quot;탭에서 35mm 2 FOV를 변경하고 컴퓨터의 기본 설정을 유지합니다. 순서를 실행하려면 시작을 클릭하고 심장은 FOV의 중심에 있지 않은 경우, 동물 홀더의 위치를​​ 조정할 RF 코​​일 리튠 다시 정찰 이미지를 얻는다. </li><li> &quot;연구&quot;탭에서 &quot;GEMS&quot;순서 버튼을 클릭 한 후 단축과 ​​마음 (20, 21)의 긴 축을 따라 두 개의 직교 평면을 얻기 위해 해당 &quot;획득&quot;탭을 획득 매개 변수를 입력합니다. 참고 : 그라데이션 에코 검사에 대한 일반적인 인수 매개 변수는 다음과 같습니다 슬라이스 두께 1 ㎜, 반복 시간 (TR), 200 밀리 초; 에코 시간 (TE), 2.67 밀리 초 (최소); 플립 각도 25 °; 면내 매트릭스 크기 128 x 128의; FOV, 22mm2; 인수의 수, 4; 1 분 30 초 대략 획득 시간. </li><li> &quot;전진&quot;탭에서 LV 해부학 및 기능 매개 변수를 측정하기 위해 맥박 산소 측정기 - 게이트 짧은 축 시네 MR 이미지를 수집하기 위해 &quot;CINE&quot;순서를 선택합니다. 마우스를 가져 가면 및 드래그하여 심장의 긴 축보기를 기반으로 영상 조각의 위치와 각도를 조정합니다. 그라데이션 에코 시네 순서 얻기 위해 &quot;획득&quot;탭에서 다음과 같은 이미지 매개 변수를 입력 : TR, 500 밀리 초; TE, 5 밀리 초; FOV, 22mm 2; 인수 매트릭스, 256 X 256; 슬라이스 두께 1mm; 인수의 수, 8; 프레임 수, 10; 17 분 ~의 획득 시간. 획득을 시작하려면 시작을 클릭합니다. </li><li> 이미징 소프트웨어의 &quot;I / O&quot;탭을 사용 DICOM 형식으로 획득 된 영상을 변환하고 처리를 위해 데이터 센터에 대응하는 파일을 전송. </li><li> 촬상 과정의 끝에서, 모든오우 마우스는 필터 탑 케이지 내에서 마취에서 복구 할 수 있습니다. 그들은 흉골 드러 누움을 유지하고 필요에 따라 추가 연구를 위해 그들을 유지하기 위해 충분한 의식을 되 찾을 때까지 무인 쥐를 두지 마십시오. </li></ol> 심장 자기 공명 현미경 이미징의 4. 데이터 분석 <ol><li> LV (19)의 해부학 적 및 기능적 매개 변수를 분석하는 세그먼트의 소프트웨어를 사용합니다. &quot;열기 이미지 파일 (들)&quot; &quot;파일&quot;메뉴의 하위 메뉴를 사용하여 소프트웨어에 DICOM 형식 시네 이미지를로드하여. GUI의 이미지 타입과 이미지 뷰 평면으로 &#39;짧은 축 중반 심실&#39;와 영상 기술, &#39;씨네&#39;로 &#39;MRGE&#39;를 선택합니다. </li><li> 를 통해 최종 심장 확장 및 최종 수축기에 사용되는 시간 프레임을 지정하는 &quot;다이 애스 털리을 끝으로 현재 기간을 설정&quot;을 각각 &quot;편집&quot;메뉴의 하위 메뉴 &quot;수축기을 끝으로 현재 기간을 설정합니다.&quot; </li><li>먼저 &quot;LV&quot;명령 단추를 클릭 한 다음 &quot;엔도&quot;과 오른쪽 하단 패널에 &quot;EPI&quot;명령 버튼을 수동으로 각각 좌심실 내막과 외막을 그립니다. 계산의 정확도를 증가시키기 위해 대응하는 커맨드 버튼을 눌렀을하여 유두근을 제거한다. </li><li> 이러한 이완기 볼륨, 수축기 볼륨, 뇌졸중 볼륨, 그리고 오른쪽 상단 패널의 방출 분율로 정량화 된 LV 매개 변수를 참조하십시오. 같은 두께, 및 심실 직경 22로 LV 매개 변수를 측정하는 &quot;기타&quot;명령 버튼을 누른 다음, &quot;측정 캘리퍼스&quot;명령 단추를 클릭하십시오. </li><li> 필요에 따라 이미지를 재 처리 &#39;. 매트&#39;형식의 세분화를 포함하여 이미지를 저장하기 위해 &quot;파일&quot;메뉴의 &quot;이미지 스택 및 분할 모두 저장&quot;메뉴를 클릭합니다. </li></ol>

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Validation by calibrated ventricular angiography.</a> Circulation. 82 (1), 154-163 (1990).</li><li>Hiba, B., 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=Cardiac+and+respiratory+double+self-gated+cine+MRI+in+the+mouse+at+7+T.">Cardiac and respiratory double self-gated cine MRI in the mouse at 7 T.</a> Magn Reson Med. 55 (3), 506-513 (2006).</li><li>Bryant, 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=Cardiac+failure+in+transgenic+mice+with+myocardial+expression+of+tumor+necrosis+factor-alpha.">Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha.</a> Circulation. 97 (14), 1375-1381 (1998).</li><li>Neu, N., 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=Cardiac+myosin-induced+myocarditis+as+a+model+of+postinfectious+autoimmunity.">Cardiac myosin-induced myocarditis as a model of postinfectious autoimmunity.</a> Eur Heart J. 12 Suppl D, 117-120 (1991).</li><li>Neumann, D. A., 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=Induction+of+multiple+heart+autoantibodies+in+mice+with+coxsackievirus+B3-+and+cardiac+myosin-induced+autoimmune+myocarditis.">Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis.</a> J Immunol. 152 (1), 343-350 (1994).</li><li>Rose, N. R., 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=Postinfectious+autoimmunity:+two+distinct+phases+of+coxsackievirus+B3-induced+myocarditis.">Postinfectious autoimmunity: two distinct phases of coxsackievirus B3-induced myocarditis.</a> Ann N Y Acad Sci. 475, 146-156 (1986).</li><li>Farmer, J. B., Levy, G. 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No conflicts of interests were declared.

이 연구는자가 면역 심근염으로 영향을받는 생쥐의 심장 이상을 확인할 수있는 비 침습적 인 도구로 MRM 절차 및 유틸리티를 설명합니다. EAM의 조직 학적 특징은 인간의 후 사구체 심근염과 유사하기 때문에, 마우스 모델은 일반적으로 심근 부상 23-25의 면역 메커니즘을 묘사하기 위해 사용된다. 그러나, 심근염 영향 동물은 임상 적으로 정상 나타나고, 진단은 실험 7의 종단에서 ?...

심장 마비가 사망의 주요 원인이며, 심근염 젊은 청소년 1 심장 마비의 하나의 주된 원인이다. 심근염으로 영향을받는 대부분의 환자는 증상이 남아 있고 질병은 저절로 2 해결됩니다. 그러나, 영향을받는 사람들의 10 ~ 20 %는 확장 성 심근증 (DCM) 3로 이어지는, 만성 질환을 개발할 수 있습니다. 다양한 동물 모델은 심근염의 면역 기전을 연구하기 위해 개발되었다. 질병은 심장 마이 오신 중쇄 (Myhc)-α 또는 immunodominant 펩티드 조각 또는 콕 사키 바이러스의 B3 4-9와 같은 병원체 감염에 의해 동물을 면역에 의해 심근염에 민감한 A / J와의 Balb / C 마우스에서 유도 할 수있다. 이 연구는 A / J 생쥐 334-352 유도 심근염을 Myhc가-α 포함한다. 심근 침입을 보여주는에도 불구하고, 심근염 영향을받는 동물은 임상 적으로 정상 표시; 진단은 염증 7에 대한 마음의 조직 학적 평가를 기반으로ND 심 초음파 10. 자기 공명 현미경 (MRM)을 분 혈관의 레벨 (최대 10 μm의 직경)에 기능적 세부의 평가를 허용하는, 고해상도 입체 평면 심혈관 이미징을 얻기 위해 일반적으로 사용되는 방법이지만, 해상력이 수준은 해상도는 일반적으로 1mm 11-14까지 수득되는 루틴 자기 공명 영상 (MRI) 스캔 절차로 달성하지. 이 질병 과정 (14)의 초기 시점에 성능 파라미터를 도출하는 것도 고해상도 이미지의 획득을 허용하는 상태로 MRM는 이점을 제공한다. 임상 적으로, MRM 영상은 광범위하게 병에 걸린 심장, 폐, 뇌 15-17의 기능 매개 변수를 연구에 적용하고있다. 본 연구에서는 면역 심근염으로 영향을받는 A / J 생쥐의 심장 이상을 확인할 수있는 비 침습적 인 도구로 MRM 기술의 사용이 표시됩니다. 특히, T그는 MRM 영상은 허용 등 합리적인 정확도 (18)와 좌심실 이완 기말 용적 및 박출계수 (EF) 등의 기능 매개 변수의 정량화. 각 파라미터의 정의는 : LV 단부 이완기 볼륨 이완기 사이클의 끝에서 좌심실에서 혈액의 양 및 박출계수, 행정 용적 / 이완 기말 볼륨. 데이터 분석은 자기 공명 스캐너 (19)에 의해 취득 처리 DICOM 호환 심장 혈관 이미지를 위해 개발 된 자유롭게 사용할 세그먼트 소프트웨어를 사용하여 수행됩니다. 데이터는 건강한 쥐에서 이러한 기능 매개 변수와 비교하여, 좌심실 이완 기말 용적, 뇌졸중 볼륨과 구혈률의 감소에 해당하는 myocarditic 동물의 좌심실 벽의 두께 증가를 공개했다.

<table border="0" cellpadding="0" cellspacing="0" width="1185">
	<tbody>
		<tr height="25">
			<td height="25" style="height:25px;width:509px;">Myhc-a 334-352 (DSAFDVLSFTAEEKAGVYK)</td>
			<td style="width:364px;">Neopeptide, Cambridge, MA</td>
			<td style="width:145px;"></td>
			<td style="width:167px;">Store at 4&#959;C</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">CFA</td>
			<td style="width:364px;">Sigma Aldrich, St Louis, MO</td>
			<td style="width:145px;">5881</td>
			<td>Store at 4&#959;C</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">MTB&#160; H37Rv extract&#160;</td>
			<td>Difco Laboratories, Detroit, MI</td>
			<td>231141</td>
			<td>Store at 4&#959;C</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">PT</td>
			<td>List Biologicals Laboratories, Campbell, CA</td>
			<td>181</td>
			<td>Store at 4&#959;C</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">1x PBS&#160;</td>
			<td>Corning, Manassas, VA</td>
			<td>21-040-CV</td>
			<td>Store at 4&#959;C</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isoflurane&#160;</td>
			<td>Piramal Healthcare, Mumbai, India</td>
			<td>NDC66794-013-25</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Female A/J mice&#160;</td>
			<td>Jackson Laboratories, Bar Harbor, ME</td>
			<td>646</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Leur-lok sterile 1 ml syrringe</td>
			<td>BD, Franklin Lakes, NJ</td>
			<td>309628</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Leur-lok sterile 3 ml syrringe</td>
			<td>BD, Franklin Lakes, NJ</td>
			<td>309657</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile needle, 18 G</td>
			<td>BD, Franklin Lakes, NJ</td>
			<td>305195</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile needle, 27 1/2 G</td>
			<td>BD, Franklin Lakes, NJ</td>
			<td>305109</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3-way stopcock&#160;</td>
			<td>Smiths Medical ASD, Inc. Dublin, OH</td>
			<td>MX5311L</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Kerlix gauze bandage rolls&#160;</td>
			<td>Covidien, Mansfield, MA</td>
			<td>6720</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Kimwipes</td>
			<td>Kimberly-Clark Professional, Roswell, GA</td>
			<td>34155</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Protouch Stockinette&#160;</td>
			<td>Medline Industries, Mundelein, IL</td>
			<td>30-1001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile surgical scissors and forceps</td>
			<td style="width:364px;">INOX tool Corporation</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Micro oven</td>
			<td style="width:364px;">GE Healthcare,&#160;</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">ThermiPAQ hot and cold therapy system&#160;</td>
			<td>Theramics Corporation, Springfield, IL</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Reptile heating lamp&#160;</td>
			<td>Energy Savers Unlimited, Inc. Carson, CA</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3M Transpore tapes&#160;</td>
			<td>Target Corporation, MN</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Up and Up Polymyxin B sulfate/Bacitracin/Neomycin sulfate antibiotic ointment</td>
			<td>Target Corporation, MN</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">North Safety DeciDamp-2PVC foam ear plugs</td>
			<td style="width:364px;">North Safety Products, Smithfield, RI</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Cotton tipped applicator, 6&#8217;&#8217; wooden stem&#160;</td>
			<td>Jorgensen Laboratories, Inc. Loveland, CO</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Anesthesia induction chamber&#160;</td>
			<td>Summit Anesthesia Solutions, Ann Harbor, MI</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Summit Anesthesia Support system for regulating flow of anesthesia&#160;</td>
			<td>Summit Anesthesia Solutions, Ann Harbor, MI</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Specially designed animal holder</td>
			<td>Agilent Technologies, Santa Clara, CA</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bickford&#160;Omnicon F/Air&#160;anesthesia gas filter unit&#160;</td>
			<td>A.M. Bickford, Inc. Wales Center, NY</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pulse-oximeter module, MR compatible small animal monitoring and gating system&#160;</td>
			<td>Small Animal Instruments, Inc. Stony Brook, NY</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Oxygen cylinder&#160;</td>
			<td>Matheson-Tri Gas, North-Central Zone, Lincoln, NE</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Gas regulator&#160;</td>
			<td>Western Medica, West Lake, OH</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Signal breaking module, MR compatible small animal monitoring and gating system</td>
			<td>Small Animal Instruments, Inc. Stony Brook, NY</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">9.4 T (400 MHZ) 89 mm vertical core bore MR scanner&#160;</td>
			<td>Agilent Technologies, Santa Clara, CA</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">4-cm millipede micro-imaging RF coil&#160;</td>
			<td>Agilent Technologies, Santa Clara, CA</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">SAM PC monitor&#160;</td>
			<td>Small Animal Instruments, Inc. Stony Brook, NY</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Quantitative Medical Image analysis software&#160;</td>
			<td colspan="3">http://segment.heiberg.se;&#160; Segment v1.8 R1430,&#160; Medviso, Oresunds region, Sweden</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Matlab software&#160;</td>
			<td>The Mathworks, Inc.&#160; Natick, MA</td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Computer-Unix operating system</td>
			<td style="width:364px;"></td>
			<td style="width:145px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse

심근염 심근의 염증이지만, 질병의 그러한 영향 쇼 임상 증상 만 ~ 10 %. 심근 손상의 면역 이벤트를 연구하기 위해, 심근염의 다양한 마우스 모델이 널리 사용되어왔다. 이 연구는 심장 마이 오신 중쇄 (Myhc)-α A / J 생쥐에서 334-352로 유발 된 면역 심근염 (EAM)를 포함; 영향을받는 동물은 림프 구성 심근염을 개발하지만 뚜렷한 임상 증상과 함께. 이 모델에서, 비 침습 양상으로 자기 공명 현미경 (MRM)의 유틸리티가 표시됩니다 Myhc-α 334-352으로 예방 접종을 동물의 심장 구조 및 기능 변화를 확인합니다. EAM 건강한 마우스는 9.4 T (400 메가 헤르츠) 4cm 노래기 무선 주파수 이미징 프로브와 100 G / cm 트리플 축 그라데이션을 갖춘 89mm 수직 코어 구멍 스캐너를 사용하여 몇 군데 있었다. 심장 이미지는 애니보기 구배 에코 기반 시네 펄스 시퀀스를 사용하여 마취 된 동물로부터 취득하고 있었다LS는 호흡과 맥박 산소 측정기에 의해 감시했다. 분석은 건강한 쥐에 비해 심실의 내부 직경에 상응하는 감소로, EAM 마우스의 심실 벽의 두께 증가를 공개했다. 데이터는 염증이 마음에 형태 학적 및 기능적 변화는 살아있는 동물에서 비 침습적 모니터링 MRM으로 할 수있는 것이 좋습니다. 결론적으로, MRM은 진행과 회귀 병원체에 의한 질병에 심근 부상뿐만 아니라 치료에 반응을 평가하는 이점을 제공한다.

이 보고서에서, EAM으로 영향을받는 동물의 마음의 구조와 기능의 변화를 결정하는 비 침습 양상으로 MRM 기술의 유틸리티가 표시됩니다. 심근염은 CFA 7 Myhc-α 334-352으로 동물을 면역에 의해 A / J 생쥐에서 유도하고, 동물은 21 일 후 예방 접종에 MRM 실험을 실시 하였다. MRM 영상은 트리플 축 기울기 (최대 강도 100 G / cm)가 장착 된 89mm 수직 구멍 자석을 사용하여 9.4 T (양성자 400 메가 헤르츠)에...

Watch this Scientific Journal Video about Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse at JoVE.com

Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse

This study demonstrates the successful establishment of magnetic resonance microscopy imaging as a non-invasive tool to assess the cardiac abnormalities in mice affected with autoimmune myocarditis. The data indicate that the technique can be used to monitor the disease-progression in live animals.

마우스에있는 자기 공명 현미경 영상으로 실험자가 면역 심근염에있는 심장의 이상 유무 비 침습적 평가

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events ...

noninvasive-assessment-cardiac-abnormalities-experimental-autoimmune

Research

JoVE Journal

Medicine

9.8K 조회수.  University of Nebraska-Lincoln. This study demonstrates the successful establishment of magnetic resonance microscopy imaging as a non-invasive tool to assess the cardiac abnormalities in mice affected with autoimmune myocarditis. The data indicate that the technique can be used to monitor the disease-progression in live animals.

비디오: Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

기능 추적을 사용하여 자기 공명이 유래 심근 스트레인 평가

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

연구

의학

Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.
For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg1. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula1. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).
MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified2-4. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions5,6. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated, respectively. DCE-US allows for real-time imaging of vascularization in bone metastases after injection of microbubbles7.
In conclusion, in a model of site-specific breast cancer bone metastases multi-modal imaging techniques including MRI, VCT and US offer complementary information on morphology and functional parameters of angiogenesis in these skeletal lesions.

In the pathogenesis of bone metastasis, angiogenesis is a crucial process and therefore represents a target for imaging and therapy. Here, we present a rat model of site-specific breast cancer bone metastasis and describe strategies to non-invasively image angiogenesis in vivo using magnetic resonance imaging, volumetric computed tomography and ultrasound.

자기 공명 영상, 체적 계산의 Tomography 및 초음파를 이용한 유방암의 뼈 전이의 누드 쥐 모델에서 Angiogenesis의 멀티 모달 이미징

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell ...

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

neurodegenerative 질병의 분석에서 확산 텐서 자기 공명 영상

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

Implanting Glass Spinal Cord Windows in Adult Mice with Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) in adult rodents is the standard experimental model for studying autonomic demyelinating diseases such as multiple sclerosis. Here we present a low-cost and reproducible glass window implantation protocol that is suitable for intravital microscopy and studying the dynamics of spinal cord cytoarchitecture with subcellular resolution in live adult mice with EAE. Briefly, we surgically expose the vertebrae T12-L2 and construct a chamber around the exposed vertebrae using a combination of cyanoacrylate and dental cement. A laminectomy is performed from T13 to L1, and a thin layer of transparent silicone elastomer is applied to the dorsal surface of the exposed spinal cord. A modified glass cover slip is implanted over the exposed spinal cord taking care that the glass does not directly contact the spinal cord. To reduce the infiltration of inflammatory cells between the window and spinal cord, anti-inflammatory treatment is administered every 2 days (as recommended by ethics committee) for the first 10 days after implantation. EAE is induced only 2-3 weeks after the cessation of anti-inflammatory treatment.
Using this approach we successfully induced EAE in 87% of animals with implanted windows and, using Thy1-CFP-23 mice (blue axons in dorsal spinal cord), quantified axonal loss throughout EAE progression. Taken together, this protocol may be useful for studying the recruitment of various cell populations as well as their interaction dynamics, with subcellular resolution and for extended periods of time. This intravital imaging modality represents a valuable tool for developing therapeutic strategies to treat autoimmune demyelinating diseases such as EAE.

We describe a method for implanting and maintaining glass windows over the exposed spinal cords of adult mice for studying experimental autoimmune encephalomyelitis. These windows provide chronic optical access to the spinal cord for monitoring cell dynamics at the subcellular level in live animals using two-photon microscopy.

실험자가 면역 뇌척수염 성인 마우스에 유리 척수 Windows를 이식

Experimental autoimmune encephalomyelitis (EAE) in adult rodents is the standard experimental model for studying autonomic demyelinating diseases such as ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

마우스 대뇌 저산소증 - 허혈 동안 동시 PET / MRI 영상

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

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 ...

Quantitative Visualization of Leukocyte Infiltrate in a Murine Model of Fulminant Myocarditis by Light Sheet Microscopy

Light-sheet fluorescence microscopy (LSFM), in combination with chemical clearing protocols, has become the gold standard for analyzing fluorescently labelled structures in large biological specimens, and is down to cellular resolution. Meanwhile, the constant refinement of underlying protocols and the enhanced availability of specialized commercial systems enable us to investigate the microstructure of whole mouse organs and even allow for the characterization of cellular behavior in various live-cell imaging approaches. Here, we describe a protocol for the spatial whole-mount visualization and quantification of the CD45+ leukocyte population in inflamed mouse hearts. The method employs a transgenic mouse strain (CD11c.DTR)that has recently been shown to serve as a robust, inducible model for the study of the development of fulminant fatal myocarditis, characterized by lethal cardiac arrhythmias. This protocol includes myocarditis induction, intravital antibody-mediated cell staining, organ preparation, and LSFM with subsequent computer-assisted image post-processing. Although presented as a highly-adapted method for our particular scientific question, the protocol represents the blueprint of an easily adjustable system that can also target completely different fluorescent structures in other organs and even in other species.

Here, we describe a light-sheet microscopy approach to visualize the cardiac CD45+ leukocyte infiltrate in a murine model of aseptic fulminant myocarditis, which is induced by the intratracheal diphtheria toxin treatment of CD11c.DTR mice.

Light Sheet Microscopy에 의한 심근 성 심근염의 Murine 모델에서의 백혈구 침윤의 정량적 시각화

Light-sheet fluorescence microscopy (LSFM), in combination with chemical clearing protocols, has become the gold standard for analyzing fluorescently ...

Cardiac Magnetic Resonance Imaging at 7 Tesla

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher magnetic field strengths and potentially provides improved signal contrast and spatial resolution. While promising results have been achieved, ultra-high field CMR is challenging due to energy deposition constraints and physical phenomena such as transmission field non-uniformities and magnetic field inhomogeneities. In addition, the magneto-hydrodynamic effect renders the synchronization of the data acquisition with the cardiac motion difficult. The challenges are currently addressed by explorations into novel magnetic resonance technology. If all impediments can be overcome, ultra-high field CMR may generate new opportunities for functional CMR, myocardial tissue characterization, microstructure imaging or metabolic imaging. Recognizing this potential, we show that multi-channel radio frequency (RF) coil technology tailored for CMR at 7 Tesla together with higher order B0 shimming and a backup signal for cardiac triggering facilitates high fidelity functional CMR. With the proposed setup, cardiac chamber quantification can be accomplished in examination times similar to those achieved at lower field strengths. To share this experience and to support the dissemination of this expertise, this work describes our setup and protocol tailored for functional CMR at 7 Tesla.

The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

쥐 일반적인 경 동맥에 단계 대조 자기 공명 영상

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Quantification of Levator Ani Hiatus Enlargement by Magnetic Resonance Imaging in Males and Females with Pelvic Organ Prolapse

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while evacuating acoustic gel, using a horizontally oriented 1.5 T magnetic resonance (MR) scanner. On midsagittal images, the vertical distance of pelvic organs is measured in millimeters relative to the hymen plane (female) and to the lower border of the symphysis pubis (male), preceded by - (above) or + ( below) signs. On axial images, the levator ani area is calculated in square centimeters with a free-hand tracing method from three key images, passing through the midsymphysis (level I), tangential to the lower border of the symphysis (level II), and at the maximal anterior rectal wall bulging (level III). Areas at rest and strained are compared to find evidence of a percentage of increase. The purpose is to provide objective evidence of the maximal extent of pelvic organs descent and hiatus enlargement without the interference of foreign objects or the examiner&#39;s proximity, so as to overcome the limitations of pelvic examination and transperineal sonography (i.e., subjectivity and sex-related limitations [female only]).

Here we present a protocol to standardize the measurement of the levator ani hiatus size&#160;by magnetic resonance imaging. The purpose is to extract biomechanical inferences from image analysis by comparing resting and straining values in patients of both sexes with pelvic prolapse, using consistent anatomical bony landmarks.

남성 및 여성 골반 기관 탈출으로에서 자기 공명 영상에 의해 Levator Ani 틈새 확대의 정량화

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while ...