Free-breathing 3D whole-heart joint T₁/T₂ mapping and water/fat imaging at 0.55 T

Purpose: To develop and validate a highly efficient motion compensated free-breathing isotropic resolution 3D whole-heart joint T 1/T 2 mapping sequence with anatomical water/fat imaging at 0.55 T. Methods: The proposed sequence takes advantage of shorter T 1 at 0.55 T to acquire three interleaved water/fat volumes with inversion-recovery preparation, no preparation, and T 2 preparation, respectively. Image navigators were used to facilitate nonrigid motion-compensated image reconstruction. T 1 and T 2 maps were jointly calculated by a dictionary matching method. Validations were performed with simulation, phantom, and in vivo experiments on 10 healthy volunteers and 1 patient. The performance of the proposed sequence was compared with conventional 2D mapping sequences including modified Look-Locker inversion recovery and T 2-prepared balanced steady-SSFP sequence. Results: The proposed sequence has a good T 1 and T 2 encoding sensitivity in simulation, and excellent agreement with spin-echo reference T 1 and T 2 values was observed in a standardized T 1/T 2 phantom (R 2 = 0.99). In vivo experiments provided good-quality co-registered 3D whole-heart T 1 and T 2 maps with 2-mm isotropic resolution in a short scan time of about 7 min. For healthy volunteers, left-ventricle T 1 mean and SD measured by the proposed sequence were both comparable with those of modified Look-Locker inversion recovery (640 ± 35 vs. 630 ± 25 ms [p = 0.44] and 49.9 ± 9.3 vs. 54.4 ± 20.5 ms [p = 0.42]), whereas left-ventricle T 2 mean and SD measured by the proposed sequence were both slightly lower than those of T 2-prepared balanced SSFP (53.8 ± 5.5 vs. 58.6 ± 3.3 ms [p &lt; 0.01] and 5.2 ± 0.9 vs. 6.1 ± 0.8 ms [p = 0.03]). Myocardial T 1 and T 2 in the patient measured by the proposed sequence were in good agreement with conventional 2D sequences and late gadolinium enhancement. Conclusion: The proposed sequence simultaneously acquires 3D whole-heart T 1 and T 2 mapping with anatomical water/fat imaging at 0.55 T in a fast and efficient 7-min scan. Further investigation in patients with cardiovascular disease is now warranted.</p

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Quantitative cardiovascular magnetic resonance: extracellular volume, native T1 and 18F-FDG PET/CMR imaging in patients after revascularized myocardial infarction and association with markers of myocardial damage and systemic inflammation

Abstract Background Characterization of tissue integrity and inflammatory processes after acute myocardial infarction (AMI) using non-invasive imaging is predictive of patient outcome. Quantitative cardiovascular magnetic resonance (CMR) techniques such as native T1 and extracellular volume (ECV) mapping as well as 18F-FDG positron emission tomography (PET) imaging targeting inflammatory cell populations are gaining acceptance, but are often applied without assessing their quantitative potential. Using simultaneously acquired PET/CMR data from patients early after AMI, this study quantitatively compares these three imaging markers and investigates links to blood markers of myocardial injury and systemic inflammatory activity. Methods A total of 25 patients without microvascular obstruction were retrospectively recruited. All imaging was simultaneously performed 5 ± 1 days after revascularization following AMI on an integrated 3T PET/MRI scanner. Native and post-contrast T1 data were acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, ECV maps were calculated using individually sampled hematocrit. 18F-FDG PET was executed after 1 day of dietary preparation, 12 h of fasting, and administration of heparin. ECV, 18F-FDG and native T1 data were compared mutually as well as to peak counts of peripheral blood markers (creatine kinase, creatine kinase-MB, troponin, leukocytes, monocytes) and infarct size. Results High intra-patient correlations of relative ECV, 18F-FDG PET and native T1 signal increases were observed in combination with no inter-patient correlation of maximum absolute values at the infarct center, suggesting well-colocalized but physiologically diverse processes begetting the respective image signals. Comparison of maximum image signals to markers of myocardial damage and systemic inflammation yielded highly significant correlations of ECV to peak creatine kinase-MB and overall infarct size as well as between native T1 and peak monocyte counts. Conclusions Absolute native T1 values at the infarct core early after AMI can be linked to the systemic inflammatory response independent of infarct size. Absolute ECV at the infarct core is related to both infarct size and blood markers of myocardial damage