Marcello Panagia

Abnormal function and glucose metabolism in the type-2 diabetic db/db mouse heart.

This study examined cardiac function and glucose metabolism in the 6-month-old db/db mouse, a model of type-2 diabetes. Cine magnetic resonance spectroscopy (MRI) was used to measure cardiac function in vivo. The db/db mice had decreased heart rates (17%, p<0.01) and stroke volumes (21%, p<0.05) that resulted in lower cardiac output (35%, p<0.01) than controls. Although there was no difference in ejection fraction between the 2 groups, db/db mouse hearts had a 35% lower maximum rate of ejection (p<0.01) than controls. In a protocol designed to assess maximal insulin-independent glucose uptake, hearts were isolated and perfused in Langendorff mode and subjected to 0.75 mL.min(-1).(g wet mass)(-1) low flow ischemia for 32 min. Glucose uptake during ischemia was 21% lower than in controls, and post-ischemic recovery of cardiac function was decreased by 30% in db/db mouse hearts (p<0.05). Total cardiac GLUT 4 protein was 56% lower (p<0.01) in db/db mice than in controls. In summary, the db/db mouse has abnormal left ventricular function in vivo, with impaired glucose uptake during ischemia, leading to increased myocardial damage.

Contrast-Enhanced Ultrasound: A Novel Noninvasive, Nonionizing Method for the Detection of Brown Adipose Tissue in Humans

BACKGROUND Brown adipose tissue (BAT) consumes glucose when it is activated by cold exposure, allowing its detection in humans by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT). The investigators recently described a novel noninvasive and nonionizing imaging method to assess BAT in mice using contrast-enhanced ultrasound (CEUS). Here, they report the application of this method in healthy humans. METHODS Thirteen healthy volunteers were recruited. CEUS was performed before and after cold exposure in all subjects using a continuous intravenous infusion of perflutren gas-filled lipid microbubbles and triggered imaging of the supraclavicular space. The first five subjects received microbubbles at a lower infusion rate than the subsequent eight subjects and were analyzed as a separate group. Blood flow was estimated as the product of the plateau (A) and the slope (β) of microbubble replenishment curves. All underwent (18)F-FDG PET/CT after cold exposure. RESULTS An increase in the acoustic signal was noted in the supraclavicular adipose tissue area with increasing triggering intervals in all subjects, demonstrating the presence of blood flow. The area imaged by CEUS colocalized with BAT, as detected by ¹⁸F-FDG PET/CT. In a cohort of eight subjects with an optimized CEUS protocol, CEUS-derived BAT blood flow increased with cold exposure compared with basal BAT blood flow in warm conditions (median Aβ = 3.3 AU/s [interquartile range, 0.5-5.7 AU/s] vs 1.25 AU/s [interquartile range, 0.5-2.6 AU/s]; P = .02). Of these eight subjects, five had greater than twofold increases in blood flow after cold exposure; these responders had higher BAT activity measured by (18)F-FDG PET/CT (median maximal standardized uptake value, 2.25 [interquartile range, 1.53-4.57] vs 0.51 [interquartile range, 0.47-0.73]; P = .02). CONCLUSIONS The present study demonstrates the feasibility of using CEUS as a noninvasive, nonionizing imaging modality in estimating BAT blood flow in young, healthy humans. CEUS may be a useful and scalable tool in the assessment of BAT and BAT-targeted therapies.

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LVs of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy.

Feasibility of a radiation dose conserving CT protocol for myocardial function assessment

OBJECTIVE Assessment of myocardial function can be performed at higher noise levels than necessary for coronary arterial evaluation. We evaluated image quality and radiation exposure of a dose-conserving function-only acquisition vs retrospectively electrocardiogram(ECG)-gated coronary CTA with automatic tube current modulation. METHODS Of 26 patients who underwent clinically indicated coronary CTA for coronary and function evaluation, 13 (Group I) underwent prospectively ECG-triggered coronary CTA, followed by low-dose retrospectively ECG-gated scan for function (128-slice dual-source, 80 kVp; reference tube current, 100 mA; 8-mm-thick multiplanar reformatted reconstructions) performed either immediately (n = 6) or after 5- to 10-min delay for infarct assessment (n = 7). 13 corresponding controls (Group II) underwent retrospectively ECG-gated protocols (automatic tube potential selection with CARE kV/CARE Dose 4D; Siemens Healthcare, Forchheim, Germany) with aggressive dose modulation. Image quality assessment was performed on the six Group I subjects who underwent early post-contrast dedicated function scan and corresponding controls. Radiation exposure was based on dose-length product. RESULTS Contrast-to-noise ratio (CNR) was preserved throughout the cardiac cycle in Group I and varied according to dose modulation in Group II. Visual image quality indices were similar during end systole but were better in Group II at end diastole. Although the total radiation exposure was equivalent in Group I and Group II (284 vs 280 mGy cm), the median radiation exposure associated with only the dedicated function scan was 138 mGy cm (interquartile range, 116-203 mGy cm). CONCLUSION A low-dose retrospective ECG-gated protocol permits assessment of myocardial function at a median radiation exposure of 138 mGy cm and offers more consistent multiphase CNR vs traditional ECG-modulation protocols. This is useful for pure functional evaluation or as an adjunct to single-phase scan modes. ADVANCES IN KNOWLEDGE Radiation exposure can be limited with a tailored myocardial function CT protocol while maintaining preserved images.

Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance

Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT.

A Rare Complication of Infective Endocarditis

A 65-year-old man with a permanent pacemaker placed for atrioventricular block presented to the emergency department with 4 days of fever, gastrointestinal complaints, and back pain. On presentation, he was febrile, tachycardic, and hypotensive, with a significant leukocytosis. Urine and blood cultures grew methicillin-sensitive staphylococcus aureus in 6/6 bottles. The patient was initiated on appropriate antibiotic coverage, including nafcillin, resulting in sterilization of blood cultures. Transesophageal echocardiography revealed a vegetation on the pacing wire, likely involving the tricuspid valve, necessitating removal of the pacing lead (online-only Data Supplement Movies I and II). Four weeks into his antibiotic course, continued fevers along with a new holosystolic murmur at the apex of his heart prompted repeat echocardiography, which revealed a persistent mobile echodensity on the tricuspid valve and a new mobile echodensity on the …

Multiplexed Optical Imaging of Energy Substrates Reveals That Left Ventricular Hypertrophy Is Associated With Brown Adipose Tissue ActivationCLINICAL PERSPECTIVE

Background— Substrate utilization in tissues with high energetic requirements could play an important role in cardiometabolic disease. Current techniques to assess energetics are limited by high cost, low throughput, and the inability to resolve multiple readouts simultaneously. Consequently, we aimed to develop a multiplexed optical imaging platform to simultaneously assess energetics in multiple organs in a high throughput fashion. Methods and Results— The detection of 18F-Fluordeoxyglucose uptake via Cerenkov luminescence and free fatty acid uptake with a fluorescent C16 free fatty acid was tested. Simultaneous uptake of these agents was measured in the myocardium, brown/white adipose tissue, and skeletal muscle in mice with/without thoracic aortic banding. Within 5 weeks of thoracic aortic banding, mice developed left ventricular hypertrophy and brown adipose tissue activation with upregulation of &bgr;3AR (&bgr;3 adrenergic receptors) and increased natriuretic peptide receptor ratio. Imaging of brown adipose tissue 15 weeks post thoracic aortic banding revealed an increase in glucose (P<0.01) and free fatty acid (P<0.001) uptake versus controls and an increase in uncoupling protein-1 (P<0.01). Similar but less robust changes were seen in skeletal muscle, while substrate uptake in white adipose tissue remained unchanged. Myocardial glucose uptake was increased post-thoracic aortic banding but free fatty acid uptake trended to decrease. Conclusions— A multiplexed optical imaging technique is presented that allows substrate uptake to be simultaneously quantified in multiple tissues in a high throughput manner. The activation of brown adipose tissue occurs early in the onset of left ventricular hypertrophy, which produces tissue-specific changes in substrate uptake that may play a role in the systemic response to cardiac pressure overload.

Cardiac Magnetic Resonance (CMR) Imaging

Magnet is “always on” and therefore ANY ferromagnetic material entering the magnet room will be attracted to the bore of the magnet and potentially be a lethal projectile.