Molecular imaging of the brain-heart axis provides insights into cardiac dysfunction after cerebral ischemia.

Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm3). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days after stroke compared to sham (3.8 ± 0.8 vs 2.6 ± 0.7 %ID/g max, p < 0.001). By contrast, parenchyma topical application of vasoconstrictor endothelin-1 did not generate significant stroke damage or neuroinflammatory cell activity. MCAo evoked a modest reduction in left ventricle ejection fraction at both 1 weeks and 3 weeks after stroke (LVEF at 3 weeks: 54.3 ± 5.7 vs 66.1 ± 3.5%, p < 0.001). This contractile impairment was paralleled by elevated cardiac TSPO PET signal compared to sham (8.6 ± 2.4 vs 5.8 ± 0.7%ID/g, p = 0.022), but was independent of leukocyte infiltration defined by flow cytometry. Stroke size correlated with severity of cardiac dysfunction (r = 0.590, p = 0.008). Statistical parametric mapping identified a direct association between neuroinflammation at 7 days in a cluster of voxels including the insular cortex and reduced ejection fraction (ρ = - 0.396, p = 0.027). Suppression of microglia led to lower TSPO signal at 7 days which correlated with spared late cardiac function after MCAo (r = - 0.759, p = 0.029). Regional neuroinflammation early after cerebral ischemia influences subsequent cardiac dysfunction. Total body TSPO PET enables monitoring of neuroinflammation, providing insights into brain-heart inter-organ communication and may guide therapeutic intervention to spare cardiac function post-stroke.

Radionuclide Imaging of the Molecular Mechanisms Linking Heart and Brain in Ischemic Syndromes.

For the heart and the brain, clinical observations suggest that an acute ischemic event experienced by one organ is associated with an increased risk for future acute events and chronic dysfunction of the reciprocal organ. Beyond atherosclerosis as a common systemic disease, various molecular mechanisms are thought to be involved in this interaction. Molecular-targeted nuclear imaging may identify the contribution of factors, such as the neurohumoral, circulatory, or especially the immune system, by combining specific radiotracers with whole-body acquisition and global as well as regional multiorgan analysis. This may be integrated with complementary functional imaging markers and systemic biomarkers for comprehensive network interrogation. Such systems-based strategies go beyond the traditional organ-centered approach and provide novel mechanistic insights, information about temporal dynamics, and a foundation for future interventions aiming at optimal preservation of function of both organs.