Non-invasive assessment of experimental autoimmune myocarditis in rats using a 3 T clinical MRI scanner

Abstract

AimsThe aim of this study was to assess the use of a 3 T clinical cardiac magnetic resonance (CMR) scanner to detect injury to the heart in experimental autoimmune myocarditis (EAM). Methods and resultsThe use of 3 T CMR for the detection of cardiac injury was assessed in EAM (n ¼ 55) and control (n ¼ 10) male Lewis rats. Animals were evaluated with serial CMR imaging studies, using a 3 T scanner, and with 2D echocardiography before, and at 2 and 5 weeks after EAM induction. By CMR, regional wall motion abnormalities were noted in seven out of eight rats with myocarditis 5 weeks after induction. Subsequently, the rats developed significant left ventricular (LV) dilatation, wall thickening, and pericardial effusion. Average LV systolic and diastolic volumes increased from 131 + 10 to 257 + 20 mL (P ¼ 0.0008), and from 309 + 14 to 412 + 24 mL (P , 0.0001), and ejection fraction markedly deteriorated (from 58 + 2 to 37 + 5%; P ¼ 0.0003). Areas of fibrosis were located by late gadolinium enhancement (LGE) CMR at the subepicardium, mainly within the anterior, lateral, and inferior walls. The extent and location of LGE were highly correlated (r ¼ 0.94; P , 0.0001) with areas of myocardial fibrosis by histopathology, with 85% sensitivity and 86% specificity. ConclusionA clinical 3 T CMR scanner enables accurate detection, quantification, and monitoring of experimental myocarditis in rats, and could be used for translational research to study the pathophysiology of the disease and evaluate novel therapies.--

Noninvasive Imaging of Myocardial Inflammation in Myocarditis using 68Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

“…Although investigators have added the use of T2 magnetic resonance imaging for detection of myocardial edema 33, some have disputed its scientific basis 34. In a previous report using rat myocarditis model, abnormal magnetic resonance findings were not definite at 2 weeks after induction of myocarditis 35. In this respect, our findings showing clear 68 Ga-NOTA-MSA uptake at 2 weeks on PET after induction of myocarditis, which was earlier than myocardial edema on echocardiography, hold great promise for early diagnosis of these kinds of patients in doubt of diagnosis.…”

Upregulation of transforming growth factor-β signaling in a rat model of rotator cuff tears

“…Unlike atrophy and fatty infiltration, muscle fibrosis is difficult to quantify 17 and does not have a similar MRI correlation. Recent studies in cardiac fibrosis MRI imaging 24,25 are promising and may be translatable to skeletal muscle as well. Finally, we did not directly inhibit TGF-β in this study to confirm the importance of TGF-β in RCT muscle changes.…”

Injectable Collagen Implant Improves Survival, Cardiac Remodeling, and Function in the Early Period After Myocarditis in Rats

“…To induce experimental autoimmune myocarditis (EAM), we anesthetized 42 male Lewis rats (Harlan, Israel), aged 6 to 8 weeks, weighing ∼200 g, with a combination of ketamine–xylazine (40 mg/10 mg/kg) and subjected them to porcine cardiac myosin (PCM) immunization (M0531; Sigma-Aldrich, Israel) as described previously. 16,17 In brief, we emulsified PCM with an equal volume of complete Freund adjuvant (CFA; Difco) mixed with desiccated Mycobacterium tuberculosis H37Ra (Difco, Detroit, Michigan). On days 0 and 7, 0.2 mL of the PCM-CFA emulsion (containing 1 mg PCM) was subcutaneously injected into all animals.…”

“…Examinations were performed before induction of myocarditis, before collagen implantation, and 3, 10, and 17 days after collagen implantation. 16,17 All measurements were done blindly by an experienced technician, averaged for 3 consecutive cardiac cycles and blindly reviewed by an echocardiography expert (MSF).…”