Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.

Intracerebral Hemorrhage-Induced Cognitive Impairment in Rats Is Associated With Brain Atrophy, Hypometabolism, and Network Dysconnectivity.

The mechanisms underlying intracerebral hemorrhage (ICH)-related cognitive impairment (CI) remain unclear. Long-term structural and functional changes were investigated in the brains of healthy male and female Wistar rats after experimental ICH. Following double injection of autologous blood, rats underwent short-term (onset, 3 and 7 days) and long-term (3 and 6 months) radiological assessment and behavioral tests exploring spontaneous locomotion, anxiety-like behavior and working memory, spatial recognition memory and visual recognition memory. Volumetric and metabolic changes in brain areas were examined by 7Tesla-MRI and [18F] FDG-PET, respectively. Brain connectomic disorders and maladaptive processes were seeked through brain metabolic connectivity analysis and atrophy-related network analysis. From an initial hematoma mean volume of 23.35 ± 9.50 mm3, we found early spontaneous locomotor recovery and significant spontaneous blood resorption (≈ 40% of the initial lesion) from days 0 to 7. After 3 and 6 months, ICH rats exhibited CI in several domains as compared to the sham group (working memory: 58.1 ± 1.2 vs. 70.7 ± 1.2%, p < 0.001; spatial recognition memory: 48.7 ± 1.9 vs. 64 ± 1.8%, p < 0.001 and visual recognition memory: 0.14 ± 0.05 vs. 0.33 ± 0.04, p = 0.013, in female only). Rats that experienced ICH had remote and concomitant cerebral atrophy and hypometabolism of ipsilateral striatum, thalamus, limbic system and cortical areas (temporal and parietal lobes). Interestingly, both structural and metabolic deterioration was found in the limbic system connected to the affected site, but remotely from the initial insult. On the other hand, increased activity and functional connectivity occurred in the contralateral hemisphere. These connectomics results showed that both maladaptative and compensation processes coexist in the rat brain following ICH, even at young age and in a disease-free setting. These radiological findings deepen our understanding of ICH-related CI and may serve as biomarkers in the view of future therapeutic intervention.

Beneficial effects of atorvastatin on sex-specific cognitive impairment induced by a cerebral microhaemorrhage in mice.

BACKGROUND AND PURPOSES: Cerebral microhaemorrhages (CMHs) are associated with cognitive decline in humans. In rodents, CMHs induces cognitive impairment in male mice along with sex-specific cortical and hippocampal changes affecting neural, glial and vascular functions. Statins, have been proposed to prevent cognitive decline. We tested here the action of atorvastatin on CMH-induced cognitive impairment in a murine model of CMH. EXPERIMENTAL APPROACH: Using a multimodal approach combining behavioural tests, in vivo imaging, biochemistry and molecular biology, the effects of oral administration of atorvastatin on the sex-specific changes induced by a cortical CMH were studied in male and female mice (C57BL/6J) at 6-week post-induction using a collagenase-induced model. KEY RESULTS: Atorvastatin caused specific effects according to the sex-specific CMH-induced changes. In males, atorvastatin improved the visuospatial memory, induced a local modulation of microglial response and enhanced brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (trkB) and vascular endothelial growth factor (VEGF) expression in the cortex. In the hippocampus, atorvastatin increased glucose metabolism and modulated astrocytes morphology. In females, atorvastatin did not modulate visuospatial memory despite the increased expression of cortical BDNF and the decrease in the number of hippocampal astrocytes. Atorvastatin also induced a decrease in the expression of cortical oestrogen receptors but did not modify body weight nor serum cholesterol levels in both sexes. CONCLUSION AND IMPLICATIONS: Atorvastatin modulated the sex-specific cognitive impairment induced by the CMH with a pathophysiological impact mainly within the cortical area. It could represent a promising candidate for future sex-stratified clinical trials in patients with CMH.

Robust contour tracking in ultrasound tongue image sequences.

A new contour-tracking algorithm is presented for ultrasound tongue image sequences, which can follow the motion of tongue contours over long durations with good robustness. To cope with missing segments caused by noise, or by the tongue midsagittal surface being parallel to the direction of ultrasound wave propagation, active contours with a contour-similarity constraint are introduced, which can be used to provide 'prior' shape information. Also, in order to address accumulation of tracking errors over long sequences, we present an automatic re-initialization technique, based on the complex wavelet image similarity index. Experiments on synthetic data and on real 60 frame per second (fps) data from different subjects demonstrate that the proposed method gives good contour tracking for ultrasound image sequences even over durations of minutes, which can be useful in applications such as speech recognition where very long sequences must be analyzed in their entirety.