FDDNP binding using MR derived cortical surface maps.

OBJECTIVES: To assess quantitatively the cortical pattern profile of regional FDDNP binding to beta-amyloid and neurofibrillary tangles on MR derived cortical maps, FDDNP PET images were corrected for movement and partial volume (PV), and optimized for kernel size. METHODS: FDDNP DVR PET images from 23 subjects (7 with Alzheimer's disease (AD), 6 with mild cognitive impairment and 10 controls) were obtained from Logan analysis using cerebellum as reference. A hemispheric cortical surface model for each subject was extracted from the MRI. The same transformations were applied to the FDDNP DVR PET images to map them into the same space. The cortical map with PV correction was calculated as the ratio of the DVR cortical surface and that of the simulated map, created from the mask derived from MRI and smoothed to the PET resolution. Discriminant analysis was used to order the FDDNP DVR cortical surfaces based on subjects' disease state. Linear regression was used to assess the rate of change of DVR vs. MMSE for each hemispheric cortical surface point. RESULTS: The FDDNP DVR cortical surface corrected for movement and PV had less hemispheric asymmetry. Optimal kernel size was determined to be 9 mm. The corrected cortical surface map of FDDNP DVR showed clear spatial pattern that was consistent with the known pathological progression of AD. CONCLUSION: Correcting for movement, PV as well as optimizing kernel size provide sensitive statistical analysis of FDDNP distribution which confirms in the living brain known pathology patterns earlier observed with cognitive decline with brain specimens.

Isolation and Characterization of Mutants of Thiophene Synthesis in Tagetes erecta.

Two mutants of Tagetes erecta displaying aberrant thiophene composition were identified by screening more than 300 plants from a mutagenized M2 population using high-performance liquid chromatography analysis of root extracts. Both mutants, which may have originated from the same mutational event, contained high amounts of the C13 monothiophene 2-(but-3-en-1-ynyl)-5-(penta-1,3-diynyl)-thiophene that was previously not found in T. erecta and also high amounts of two C13 bithienyls that were absent or present at low concentrations in the wild type. The mutant phenotype was also expressed in 21 Agrobacterium rhizogenes transformed root clones derived from both mutants. Feeding experiments with root cultures derived from one mutant and from the wild type indicated that the monothiophene accumulating in the mutant is the common precursor for all bithienyl thiophenes in wild-type and mutant Tagetes erecta. These experiments also showed that one mutant is deficient in demethylation of the monothiophene.

Clathration-induced asymmetric transformation of cefadroxil.

[structure: see text] The cephalosporin antibiotic Cefadroxil can be epimerized at the alpha-carbon of its amino acid side chain using pyridoxal as the mediator. By clathration with 2,7-dihydroxynaphthalene, the desired diastereomer can be selectively withdrawn from the equilibrating mixture of epimers. In this way, an asymmetric transformation of Cefadroxil can be accomplished. This opens the possibility of the production of Cefadroxil starting from racemic p-hydroxyphenylglycine, in contrast to the current industrial synthesis that employs the D-amino acid in enantiopure form.

What is meant by "TICI"?

BACKGROUND: In 2003, Higashida et al proposed the Thrombolysis In Cerebral Infarction scale to evaluate angiographic intracranial flow. Our aim is to review how subsequently published studies define TICI. MATERIALS AND METHODS: We used the ISI Web of Knowledge and SciVerse Scopus databases to search for "TICI" and "thrombolysis in cerebral infarction" and for articles that cited the original TICI paper from January 2004 through May 2012. Articles were categorized according to their definition of the TICI categories, typically grades 0-4, with grade 2 (partial reperfusion) subdivided into 2a and 2b, and rate of contrast entry to the perfused area. In addition, we catalogued the type of redefinitions of TICI subcategory 2 and additions of new categories. RESULTS: Of 236 articles screened, 74 were included. Eight (11%) explicitly followed the TICI scale as originally defined. Thirty-seven (50%) cited Higashida but did not define their scale. Fifteen (21%) used and explained modified scales. Thirteen (18%) used the term TICI, but did not define the scale and did not cite Higashida. Eighteen (24%) specified a 2a subcategory. Nine defined grade 2a as <67% filling, 6 defined it as <50%, and 3 did not offer a percentage. Two studies added a 2c subcategory. Fifty-two (70%) used a cutoff level to define "successful reperfusion." Of these, 65% used TICI ≥2, 33% used TICI ≥2b, and 2% used TICI = 3. CONCLUSIONS: There is substantial variability in the definition and/or application of the TICI scale in the literature. This variability could considerably impact our understanding of results of revascularization studies.

Interobserver variability in retreatment decisions of recurrent and residual aneurysms.

BACKGROUND AND PURPOSE: The degree of variation in retreatment decisions for residual or recurrent aneurysms among endovascular therapists remains poorly defined. We performed a multireader study to determine what reader and patient variables contribute to this variation. MATERIALS AND METHODS: Seven endovascular therapists (4 neuroradiologists, 3 neurosurgeons) independently reviewed 66 cases of patients treated with endovascular coil embolization for ruptured or unruptured aneurysm. Cases were rated on a 5-point scale recommending for whether to retreat and a recommended retreatment type. Reader agreement was assessed by intraclass correlation coefficient and by identifying cases with a "clinically meaningful difference" (a difference in score that would result in a difference in treatment). Variables that affect reader agreement and retreatment decisions were examined by using the Wilcoxon signed-rank test, Pearson χ(2) test, and linear regression. RESULTS: Overall interobserver variability for decision to retreat was moderate (ICC = 0.50; 95% CI, 0.40-0.61). Clinically meaningful differences between at least 2 readers were present in 61% of cases and were significantly more common among neuroradiologists than neurosurgeons (P = .0007). Neurosurgeons were more likely to recommend "definitely retreat" than neuroradiologists (P < .0001). Previously ruptured aneurysms, larger remnant size, and younger patients were associated with more retreat recommendations. Interobserver variability regarding retreatment type was fair overall 0.25 (95% CI, 0.14-0.41) but poor for experienced readers 0.14 (95% CI, 0-0.34). CONCLUSIONS: There is a large amount of interobserver variability regarding the decision to retreat an aneurysm and the type of retreatment. This variability must be reduced to increase consistency in these subjective outcome measurements.

Fluid registration of diffusion tensor images using information theory.

We apply an information-theoretic cost metric, the symmetrized Kullback-Leibler (sKL) divergence, or J-divergence, to fluid registration of diffusion tensor images. The difference between diffusion tensors is quantified based on the sKL-divergence of their associated probability density functions (PDFs). Three-dimensional DTI data from 34 subjects were fluidly registered to an optimized target image. To allow large image deformations but preserve image topology, we regularized the flow with a large-deformation diffeomorphic mapping based on the kinematics of a Navier-Stokes fluid. A driving force was developed to minimize the J-divergence between the deforming source and target diffusion functions, while reorienting the flowing tensors to preserve fiber topography. In initial experiments, we showed that the sKL-divergence based on full diffusion PDFs is adaptable to higher-order diffusion models, such as high angular resolution diffusion imaging (HARDI). The sKL-divergence was sensitive to subtle differences between two diffusivity profiles, showing promise for nonlinear registration applications and multisubject statistical analysis of HARDI data.