MR myocardial perfusion imaging with k-space and time broad-use linear acquisition speed-up technique: feasibility study

The purpose of this study was to prospectively evaluate the diagnostic accuracy of a cardiovascular magnetic resonance (MR) k-space and time (k-t) broad-use linear acquisition speed-up technique (BLAST) accelerated perfusion sequence for depicting clinically relevant coronary artery disease (CAD), with use of coronary angiography as the reference standard. The local ethics committee approved this study, and informed consent was obtained from 40 patients (28 men, 12 women; mean age, 61 years +/- 8 [standard deviation]) scheduled for coronary catheterization. A balanced steady-state free precession pulse sequence (2.6 x 2.6 x 10 mm) with a net k-t acceleration factor of 3.8 (repetition time msec/echo time msec, 3.2/1.6; flip angle, 50 degrees ) was applied. Visual analysis of perfusion images and quantitative analysis of signal-time curves obtained in the myocardium were performed by using segmental myocardial upslope, peak enhancement, and their respective ratios. Visual analysis revealed sensitivity, specificity, and diagnostic accuracy of 86%, 78%, and 83%, respectively, in the detection of coronary stenoses with at least 50% luminal narrowing. Significant (P < .05) changes between ischemic and remote segments could be shown for all perfusion indexes applied. Use of myocardial perfusion imaging with k-t BLAST for accelerated data acquisition is feasible in the identification of patients with substantial CAD (coronary stenosis >or= 50%). Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/245/3/863/DC1.     

Improved bulk myocardial motion suppression for navigator-gated coronary magnetic resonance imaging

PURPOSE: To evaluate the impact of a new, cross-correlation based method for compensation of respiratory induced motion of the heart using an individually adapted three-dimensional (3D) translation or affine transformation approach. MATERIALS AND METHODS: A total of 32 patients underwent a routine cardiac MR examination. In each patient, a calibration scan was performed during free-breathing to register breathing-related motion within a 3D ellipsoid registration kernel covering the entire heart. Three navigators were employed for all three spatial dimensions (feet-head, anterior-posterior, and left-right) and the optimal translatory correction factors for each spatial dimension were determined. In addition, the cross-correlations for different motion models (no compensation, fixed 1D-translation, adapted 3D-translation, and affine transformation) were calculated. RESULTS: The mean correction factor for the feet-head direction was 0.45 +/- 0.13. Though the mean correction factors for the anterior-posterior and left-right direction were nearly zero (-0.01 +/- 0.08 and 0.02 +/- 0.09, respectively), the correction factors exceeded the amount of 0.1 in 12 (19%) and in 19 patients (30%), respectively. All motion compensation models showed significantly higher cross-correlations when compared to "no compensation" (P < 0.05). In particular, the affine transformation algorithm achieved the highest cross-correlation values (88.3 +/- 5.1%) with a significant increase compared to fixed 1D translation (84.7 +/- 6.5%, P < 0.05). CONCLUSION: A considerable number of patients demonstrated relevant breathing-related movement of the heart in the anterior-posterior or left-right direction in addition to the predominant breathing-related movement in the feet-head direction. Thus, it is recommended to compensate for all three spatial dimensions. The affine transformation algorithm combined with three navigators significantly improved breathing-related cardiac motion compensation when compared to the conventionally applied 1D translation with a fixed correction factor.     

Exogenous reelin prevents granule cell dispersion in experimental epilepsy

Temporal lobe epilepsy (TLE) is often accompanied by granule cell dispersion (GCD), a migration defect of granule cells in the dentate gyrus. We have previously shown that a decrease in the expression of reelin, an extracellular matrix protein important for neuronal positioning, is associated with the development of GCD in TLE patients. Here, we used unilateral intrahippocampal injection of kainate (KA) in adult mice which is also associated with GCD formation and a decrease of reelin expression. In this mouse epilepsy model we aimed to prevent GCD development by the application of exogenous reelin. As a prerequisite we analyzed whether the reelin signaling transduction cascade was preserved in the KA-injected hippocampus. Using in situ hybridization and Western blot analysis we found that the expression of the reelin signaling components, apolipoprotein E receptor 2, the very-low-density lipoprotein receptor and the intracellular adaptor protein disabled 1, was maintained in dentate granule cells after KA injection. Next, recombinant reelin was infused into the KA-injected hippocampus by osmotic minipumps over a period of 2 weeks. Quantitative analysis of granule cell layer width revealed a significant reduction of GCD in reelin-treated, but not in saline-infused animals when compared to KA injection alone. Our findings highlight the crucial role of reelin for the maintenance of granule cell lamination in the dentate gyrus of adult mice and show that a reelin deficiency is causally involved in GCD development.     

Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR

Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.     

Insulin augments matrix metalloproteinase-9 expression in monocytes

OBJECTIVE: Insulin resistance and hyperinsulinemia are major causes of cardiovascular morbidity and mortality. Matrix metalloproteinases (MMPs), highly expressed in activated mononuclear cells in vulnerable atherosclerotic lesions, are the main proteolytic enzymes controlling plaque stability. The aim of this study was to investigate the regulation of monocyte MMP-9 by insulin. METHODS AND RESULTS: Stimulation of MMP-9 expression by insulin was time- and concentration-dependent in human monocytic THP-1 cells. Inhibition of insulin receptor (IR) maturation via inhibition of its activating convertase furin with the pharmacological furin-inhibitor decanoyl-RVKR-chloromethylketone, as well as blocking of IGF-1R function with a IGF-1R blocking antibody, demonstrated that insulin mediates increases in MMP-9 via IR activation. Inhibition of insulin's "metabolic" phosphatidylinositol 3-kinase signaling with wortmannin (50 nmol/L) or LY294002 (2.5 micromol/L) did not prevent insulin-dependent MMP-9 induction. In contrast inhibition of insulin's "mitogenic" Ras-Raf-mitogen-activated protein kinase-kinase pathways with PD98059 (15 micromol/L) or U0126 (2 micromol/L) inhibited insulin-induced MMP-9 gelatinolytic activity in THP-1 cells. Likewise, PD98059 inhibited insulin augmented MMP-9 levels in primary human monocytes, whereas wortmannin had no effect. CONCLUSION: This study demonstrates that insulin can induce MMP-9 via mitogenic signaling pathways in monocytes, whereas phosphatidylinositol 3-kinase-dependent signaling, typically altered in insulin resistance, is not required. Induction of MMP-9 by insulin may potentially contribute to a pro-inflammatory state and the increased cardiovascular morbidity and mortality in type 2 diabetics.     

Haemophilus influenzae bacterial meningitis: residual risk; case report]

Bacterial meningitis due to Haemophilus influenzae has become a rare, albeit not exceptional occurrence since generalized vaccination against that pathogen was instated, concerning as well incapsulated b and non-b Haemophilus influenzae strains, as non-incapsulated strains. CASE REPORT: A 19-month-old fully immunized infant was referred to our hospital for bacterial meningitis. CSF analysis elicited biotype III, non-incapsulated Haemophilus influenzae. CONCLUSION: Generalizing Haemophilus influenzae preventive inoculation has revolutionized the epidemiology of bacterial meningitis; however, a residual risk exists, which deserves to be taken into account.     

Vision and visual cortical maps in mice with a photoreceptor synaptopathy: Reduced but robust visual capabilities in the absence of synaptic ribbons

How little neurotransmission in the visual system is sufficient to promote decent visual capabilities? This question is of key importance for therapeutic approaches to restore vision in patients who suffer from degenerative retinal diseases. In the retinae of mice, mutant for the presynaptic scaffolding protein Bassoon (Bsn), signal transfer at photoreceptor ribbon synapses is severely disturbed due to impaired ribbon attachment to the active zone. We have used two different behavioural tasks and optical imaging of intrinsic signals to probe vision in young and adult Bsn?/? mice and their wild-type littermates. Here we show that while visual acuity was significantly reduced in mutants compared to controls, vision guided behavioural decisions and optical imaging revealed essentially unperturbed cortical signals and retinotopy in spite of the photoreceptor synaptopathy. In addition, both vision and visual cortical maps were adult-like at 4 weeks of age. These results show that (i) while Bassoon-dependent fast exocytosis is essential for normal vision surprisingly good visual performance can be achieved in the absence of synaptic ribbons, (ii) both the development and maintenance of visual cortical maps is independent of synaptic ribbons and (iii) visual development in the mutants is completed at 4 weeks of age indicating that later developing ectopic synapses do not affect vision. Thus, the central visual system can make use of slow and weak retinal signals to subserve surprisingly robust vision.