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Detecting a Broken Heart

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Science Translational Medicine  23 May 2012:
Vol. 4, Issue 135, pp. 135ec91
DOI: 10.1126/scitranslmed.3004313

In myocarditis, heart muscle becomes inflamed. Often caused by viral infection of myocytes and the subsequent immune response to myocardial antigens, it can lead to pump failure and arrhythmia. In fact, myocarditis is a major cause of sudden death in young adults and is notoriously difficult to detect. New work by Moon et al. indicates that iron oxide nanoparticles, by enhancing the contrast in MRI, can enable noninvasive visualization of the inflammatory infiltration of phagocytes associated with myocarditis.

The current standard for diagnosis of this disease—histological assessment of several heart muscle biopsies—suffers from so many shortcomings that it is not even recommended for some patients. The sensitivity of the approach is low because the scattered inflammatory foci are frequently missed with the biopsy instrument, and the method’s invasive nature is undesirable. Conventional MRI, which reveals edema and fibrosis in the heart, has improved the diagnostic options. But Moon et al.’s results promise to enhance detection of myocarditis even further. The authors induced autoimmune myocarditis in rat hearts by injecting porcine heart myosin together with an adjuvant. This triggered a robust, inflammatory cellular infiltrate, including invasion of phagocytes such as macrophages. These cells have previously been visualized with iron oxide–nanoparticle MRI in patients with atherosclerosis, cancer, and diabetes. In the new study, administration of nanoparticles (albeit 10 mg per kilogram of iron, roughly three times the clinical dose) led to a strong signal in the inflamed myocardium. Meticulous validation experiments found the bulk of the nanoparticles in lysosomes of macrophages. We already have enough preclinical and clinical data on iron oxide MRI of inflammation to know that the approach should be successful in patients. Hopefully, this method will make dangerous, error-prone biopsies obsolete, improve detection sensitivity, and spawn better therapeutics by supporting drug development efforts.

H. Moon et al., Noninvasive assessment of myocardial inflammation by cardiovascular magnetic resonance in a rat model of experimental autoimmune myocarditis. Circulation, 1 May 2012 (10.1161/circulationaha.111.075283). [Abstract]

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