Hemorrhagic myocarditis is a potentially fatal complication of excessive levels of systemic inflammation. It has been reported in viral infection, but is also possible in systemic autoimmunity. Epicutaneous treatment of mice with the Toll-like receptor 7 (TLR-7) agonist Resiquimod induces auto-antibodies and systemic tissue damage, including in the heart, and is used as an inducible mouse model of systemic lupus erythematosus (SLE). Here, we show that overactivation of the TLR-7 pathway of viral recognition by Resiquimod treatment of CFN mice induces severe thrombocytopenia and internal bleeding, which manifests most prominently as hemorrhagic myocarditis. We optimized a cardiac magnetic resonance (CMR) tissue mapping approach for the in vivo detection of diffuse infiltration, fibrosis and hemorrhages using a combination of T₁, T₂ and T₂^* relaxation times, and compared results with ex vivo histopathology of cardiac sections corresponding to CMR tissue maps. This allowed detailed correlation between in vivo CMR parameters and ex vivo histopathology, and confirmed the need to include T₂^* measurements to detect tissue iron for accurate interpretation of pathology associated with CMR parameter changes. In summary, we provide detailed histological and in vivo imaging-based characterization of acute hemorrhagic myocarditis as an acute cardiac complication in the mouse model of Resiquimod-induced SLE, and a refined CMR protocol to allow non-invasive longitudinal in vivo studies of heart involvement in acute inflammation. We propose that adding T₂^* mapping to CMR protocols for myocarditis diagnosis improves diagnostic sensitivity and interpretation of disease mechanisms.This article has an associated First Person interview with the first author of the paper.

中文翻译：

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通过多参数定量心脏磁共振成像表征小鼠急性 TLR-7 激动剂诱发的出血性心肌炎。

出血性心肌炎是全身炎症水平过高的潜在致命并发症。在病毒感染中已有报道，但在系统性自身免疫性疾病中也有可能发生。用 Toll 样受体 7 (TLR-7) 激动剂瑞西莫德对小鼠进行皮下治疗可诱导自身抗体和全身组织损伤，包括心脏损伤，并可用作系统性红斑狼疮 (SLE) 的诱导小鼠模型。在这里，我们发现，通过瑞西莫德治疗 CFN 小鼠，病毒识别的 TLR-7 通路过度激活，会导致严重的血小板减少和内出血，其中最突出的是出血性心肌炎。我们优化了心脏磁共振 (CMR) 组织图谱方法，使用 T ₁、T ₂和 T ₂ ^*弛豫时间的组合来体内检测弥漫性浸润、纤维化和出血，并将结果与​​心脏切片的离体组织病理学结果进行比较对应于 CMR 组织图。这使得体内CMR 参数和离体组织病理学之间存在详细的相关性，并证实需要包括 T ₂ ^*测量来检测组织铁，以便准确解释与 CMR 参数变化相关的病理学。总之，我们提供了急性出血性心肌炎作为瑞西莫德诱导的 SLE 小鼠模型中的一种急性心脏并发症的详细的基于组织学和体内成像的特征，以及改进的 CMR 方案，以允许对心脏受累进行非侵入性纵向体内研究在急性炎症中。我们建议在心肌炎诊断的 CMR 方案中添加T ₂ ^{*映射可以提高诊断灵敏度和疾病机制的解释。本文有与该论文第一作者相关的第一人称采访。}