Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression

Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects.

International audienceCONTEXT: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. OBJECTIVES: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. DESIGN AND VOLUNTEERS: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. MAIN OUTCOME MEASURES: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. RESULTS: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G₀/G₁ switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). CONCLUSIONS: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity

Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity.

International audienceOBJECTIVE: To explore sex differences in the regulation of lipolysis during exercise, the lipid-mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were studied using microdialysis. RESEARCH METHODS AND PROCEDURES: Subjects matched for age, BMI, and physical fitness performed two 30-minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo(2max)) and the second test at 30% and 70% of their Vo(2max). RESULTS: In both groups, an exercise-dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine [alpha-adrenergic receptor (AR) antagonist] added to a dialysis probe potentiated exercise-induced lipolysis only in men. In a probe containing phentolamine plus propranolol (beta-AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo(2max). A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo(2max). At each exercise power, the plasma non-esterified fatty acid and glycerol concentrations were higher in women. Exercise-induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. DISCUSSION: Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. alpha(2)-Anti-lipolytic effect was functional in SCAT of men only. The major finding is that during low-to-moderate exercise periods (30% and 50% Vo(2max)), lipid mobilization in SCAT relies less on catecholamine-dependent stimulation of beta-ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin