Non-invasive thermal imaging of cardiac remodeling in mice.

Thermal infrared imaging has been suggested as a non-invasive alternative to monitor physiological processes and disease. However, the use of this technique to image internal organs, such as the heart, has not yet been investigated. We sought to determine the ability of our novel thermal image-processing algorithm to detect structural and functional changes in a mouse model of hypertension and cardiac remodeling. Twelve mice were randomly assigned to receive either the pro-inflammatory, hypertensive hormone angiotensin-II (2 mg/kg/day, n = 6) or saline (n = 6) infusion for 28 days. We performed weekly blood pressure measurements, together with serial trans-thoracic echocardiography studies and histopathological evaluation of the hearts. Thermal images were captured with a commercially available thermal camera, and images were processed by our novel algorithm which analyzes relative spatial temperature variation across the animal's thorax. We assessed cardiac inflammation by measuring inflammatory cell infiltration through flow cytometry. Angiotensin infusion increased blood pressure together with cardiac hypertrophy and fibrosis. Thermal imaging at day 28 of the experiment detected an increase in the fraction of the skin heated by the heart in angiotensin-treated mice. Thermal image findings were significantly correlated to left ventricular volume and mass parameters seen on echocardiography (r = 0.8, p < 0.01 and r = 0.6, p = 0.07). We also identified distinct changes in the spatial heat profiles of all angiotensin-treated hearts, possibly reflecting remodeling processes in the hypertensive heart. Finally, a machine learning based model using thermal imaging parameters predicted intervention status in 10 out of 11 mice similar to a model using echocardiographic measurements. Our findings suggest, for the first time, that a new thermal image-processing algorithm successfully correlates surface thermography with cardiac structural changes in mice with hypertensive heart disease.

E-selectin-targeted copolymer reduces atherosclerotic lesions, adverse cardiac remodeling, and dysfunction.

Endothelial activation with up-regulation of E-selectin adhesion molecules mediates leukocyte rolling along the vascular wall and controls inflammation in many diseases including atherosclerosis and heart failure. Therefore, we aimed to test the hypothesis that inhibition of E-selectin-mediated interactions by a new E-selectin-targeted copolymer could inhibit the progression of atherosclerosis. To target E-selectin on activated endothelium, we developed a new N-(2-hydroxypropyl)methacrylamide (HPMA)-based E-selectin binding copolymer with or without dexamethasone (Dex) (designated P-(Esbp)-Dex and P-Esbp, respectively). To determine the effect of P-(Esbp)-Dex and P-Esbp on atherosclerosis, we allocated ApoE (-/-) mice on a high fat diet, to weekly intra-peritoneal injections of either 1) P-Esbp; 2) P-(Esbp)-Dex; 3) free Dex (1 mg/kg) or 4) saline, for four weeks. Aortic atherosclerosis and left ventricular (LV) remodeling and function were assessed by serial ultrasound studies and histology. Monocytes and macrophages were characterized by flow cytometry. After four weeks of treatment, P-Esbp effectively targeted aortic atherosclerotic lesions. Both P-Esbp and P-(Esbp)-Dex reduced wall thickening of the ascending aortas. However, only the drug-free copolymer (P-Esbp) significantly decreased the areas of necrotic core in the plaques and switched spleen macrophages toward an anti-inflammatory (M2) phenotype. Furthermore, P-Esbp attenuated adverse LV remodeling and dysfunction in ApoE (-/-) mice. In summary, P-Esbp copolymer targets activated endothelial cells, regresses and stabilizes atherosclerotic plaques, and prevents adverse LV remodeling and dysfunction in ApoE (-/-) mice. Our results suggest a new, drug-free macromolecular therapy to treat vascular inflammation.