MRS glucose mapping and PET joining forces: re-evaluation of the lumped constant in the rat brain under isoflurane anaesthesia.

Although numerous positron emission tomography (PET) studies with (18) F-fluoro-deoxyglucose (FDG) have reported quantitative results on cerebral glucose kinetics and consumption, there is a large variation between the absolute values found in the literature. One of the underlying causes is the inconsistent use of the lumped constants (LCs), the derivation of which is often based on multiple assumptions that render absolute numbers imprecise and errors hard to quantify. We combined a kinetic FDG-PET study with magnetic resonance spectroscopic imaging (MRSI) of glucose dynamics in Sprague-Dawley rats to obtain a more comprehensive view of brain glucose kinetics and determine a reliable value for the LC under isoflurane anaesthesia. Maps of Tmax /CMRglc derived from MRSI data and Tmax determined from PET kinetic modelling allowed to obtain an LC-independent CMRglc . The LC was estimated to range from 0.33 ± 0.07 in retrosplenial cortex to 0.44 ± 0.05 in hippocampus, yielding CMRglc between 62 ± 14 and 54 ± 11 μmol/min/100 g, respectively. These newly determined LCs for four distinct areas in the rat brain under isoflurane anaesthesia provide means of comparing the growing amount of FDG-PET data available from translational studies.

Use of constant denaturant capillary electrophoresis of pooled blood samples to identify single-nucleotide polymorphisms in the genes (Scnn1a and Scnn1b) encoding the alpha and beta subunits of the epithelial sodium channel.

BACKGROUND: The epithelial sodium channel (ENaC) is composed of three homologous subunits: alpha, beta, and gamma. Mutations in the Scnn1b and Scnn1g genes, which encode the beta and the gamma subunits of ENaC, cause a severe form of hypertension (Liddle syndrome). The contribution of genetic variants within the Scnn1a gene, which codes for the alpha subunit, has not been investigated. METHODS: We screened for mutations in the COOH termini of the alpha and beta subunits of ENaC. Blood from 184 individuals from 31 families participating in a study on the genetics of hypertension were analyzed. Exons 13 of Scnn1a and Scnn1b, which encode the second transmembrane segment and the COOH termini of alpha- and beta-ENaC, respectively, were amplified from pooled DNA samples of members of each family by PCR. Constant denaturant capillary electrophoresis (CDCE) was used to detect mutations in PCR products of the pooled DNA samples. RESULTS: The detection limit of CDCE for ENaC variants was 1%, indicating that all members of any family or up to 100 individuals can be analyzed in one CDCE run. CDCE profiles of the COOH terminus of alpha-ENaC in pooled family members showed that the 31 families belonged to four groups and identified families with genetic variants. Using this approach, we analyzed 31 rather than 184 samples. Individual CDCE analysis of members from families with different pooled CDCE profiles revealed five genotypes containing 1853G-->T and 1987A-->G polymorphisms. The presence of the mutations was confirmed by DNA sequencing. For the COOH terminus of beta-ENaC, only one family showed a different CDCE profile. Two members of this family (n = 5) were heterozygous at 1781C-->T (T594M). CONCLUSION: CDCE rapidly detects point mutations in these candidate disease genes.

Self-navigated isotropic three-dimensional cardiac T2 mapping.

PURPOSE: To implement and characterize an isotropic three-dimensional cardiac T2 mapping technique. METHODS: A self-navigated three-dimensional radial segmented balanced steady-state free precession pulse sequence with an isotropic 1.7-mm spatial resolution was implemented at 3T with a variable T2 preparation module. Bloch equation and Monte Carlo simulations were performed to determine the influence of the heart rate, B1 inhomogeneity and noise on the T2 fitting accuracy. In a phantom study, the accuracy of the pulse sequence was studied through comparison with a gold-standard spin-echo T2 mapping method. The robustness and homogeneity of the technique were ascertained in a study of 10 healthy adult human volunteers, while first results obtained in patients are reported. RESULTS: The numerical simulations demonstrated that the heart rate and B1 inhomogeneity cause only minor deviations in the T2 fitting, whereas the phantom study showed good agreement of the technique with the gold standard. The volunteer study demonstrated an average myocardial T2 of 40.5 ± 3.3 ms and a <15% T2 gradient in the base-apex and anterior-inferior direction. In three patients, elevated T2 values were measured in regions with expected edema. CONCLUSION: This respiratory self-navigated isotropic three-dimensional technique allows for accurate and robust in vitro and in vivo T2 quantification. Magn Reson Med 73:1549-1554, 2015. © 2014 Wiley Periodicals, Inc.