当前位置: X-MOL 学术Basic Res. Cardiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis
Basic Research in Cardiology ( IF 9.5 ) Pub Date : 2022-05-29 , DOI: 10.1007/s00395-022-00936-5
Christine Quast 1 , Frank Kober 2 , Katrin Becker 1 , Elric Zweck 1 , Jasmina Hoffe 1 , Christoph Jacoby 1 , Vera Flocke 3 , Isabella Gyamfi-Poku 1 , Fabian Keyser 1 , Kerstin Piayda 1 , Ralf Erkens 1 , Sven Niepmann 4 , Matti Adam 5 , Stephan Baldus 5 , Sebastian Zimmer 4 , Georg Nickenig 4 , Maria Grandoch 6 , Florian Bönner 1 , Malte Kelm 1, 7 , Ulrich Flögel 1, 3, 7
Affiliation  

Aortic valve stenosis (AS) is the most frequent valve disease with relevant prognostic impact. Experimental model systems for AS are scarce and comprehensive imaging techniques to simultaneously quantify function and morphology in disease progression are lacking. Therefore, we refined an acute murine AS model to closely mimic human disease characteristics and developed a high-resolution magnetic resonance imaging (MRI) approach for simultaneous in-depth analysis of valvular, myocardial as well as aortic morphology/pathophysiology to identify early changes in tissue texture and critical transition points in the adaptive process to AS. AS was induced by wire injury of the aortic valve. Four weeks after surgery, cine loops, velocity, and relaxometry maps were acquired at 9.4 T to monitor structural/functional alterations in valve, aorta, and left ventricle (LV). In vivo MRI data were subsequently validated by histology and compared to echocardiography. AS mice exhibited impaired valve opening accompanied by significant valve thickening due to fibrotic remodelling. While control mice showed bell-shaped flow profiles, AS resulted not only in higher peak flow velocities, but also in fragmented turbulent flow patterns associated with enhanced circumferential strain and an increase in wall thickness of the aortic root. AS mice presented with a mild hypertrophy but unaffected global LV function. Cardiac MR relaxometry revealed reduced values for both T1 and T2 in AS reflecting subtle myocardial tissue remodelling with early alterations in mitochondrial function in response to the enhanced afterload. Concomitantly, incipient impairments of coronary flow reserve and myocardial tissue integrity get apparent accompanied by early troponin release. With this, we identified a premature transition point with still compensated cardiac function but beginning textural changes. This will allow interventional studies to explore early disease pathophysiology and novel therapeutic targets.



中文翻译:

多参数 MRI 识别小鼠主动脉瓣狭窄疾病转变分界的细微适应

主动脉瓣狭窄 (AS) 是最常见的瓣膜疾病,具有相关的预后影响。AS 的实验模型系统很少,并且缺乏同时量化疾病进展中的功能和形态的综合成像技术。因此,我们改进了急性小鼠 AS 模型以密切模拟人类疾病特征,并开发了一种高分辨率磁共振成像 (MRI) 方法,用于同时深入分析瓣膜、心肌以及主动脉形态/病理生理学,以确定早期变化AS 适应过程中的组织结构和关键过渡点。AS 是由主动脉瓣的钢丝损伤引起的。手术后 4 周,在 9.4 T 下获取电影回放、速度和弛豫图,以监测瓣膜、主动脉、和左心室 (LV)。随后通过组织学验证体内 MRI 数据,并与超声心动图进行比较。由于纤维化重塑,AS 小鼠表现出瓣膜开放受损并伴有显着的瓣膜增厚。虽然对照小鼠显示出钟形流动剖面,但 AS 不仅导致更高的峰值流速,而且还导致与增强的周向应变和主动脉根部壁厚增加相关的碎片化湍流模式。AS 小鼠出现轻度肥大但未影响整体 LV 功能。心脏 MR 弛豫测量显示 AS 中 T1 和 T2 的值均降低,反映出细微的心肌组织重塑以及线粒体功能的早期改变,以响应增强的后负荷。同时,冠状动脉血流储备和心肌组织完整性的早期损伤伴随着肌钙蛋白的早期释放而变得明显。有了这个,我们确定了一个过早的过渡点,心脏功能仍然得到补偿,但结构开始发生变化。这将使介入研究能够探索早期疾病的病理生理学和新的治疗靶点。

更新日期:2022-05-31
down
wechat
bug