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Biomedical subjects

L Ryner

Publications and source records attributed to L Ryner.

8 recordsLinked to original sources

Resampling as a cluster validation technique in fMRI.

Exploratory, data-driven analysis approaches such as cluster analysis, principal component analysis, independent component analysis, or neural network-based techniques are complementary to hypothesis-led methods. They may be considered as hypothesis generating methods. The representative time courses they produce may be viewed as alternative hypotheses to the null hypothesis, i.e., "no activation." We present here a resampling technique to validate the results of exploratory fuzzy clustering analysis. In this case an alternative hypothesis is represented by a cluster centroid. For both simulated and in vivo functional magnetic resonance imaging data, we show that by permutation-based resampling, statistical significance may be computed for each voxel belonging to a cluster of interest without parametric distributional assumptions.

Brain↗

Correlator beware: correlation has limited selectivity for fMRI data analysis.

Groups of time-courses created from fMRI data by the frequently used correlation analysis are often highly heterogeneous. This heterogeneity is due to the limited selectivity of correlation when trying to match brain time-courses to an externally imposed activation paradigm. Thus, this process unnecessarily generates many type I errors (false positives). Furthermore, as a consequence of the heterogeneity, time-courses identified and grouped by correlation may in fact describe different activations. After demonstrating this inadequacy, we give one particular approach to partition such a heterogeneous group into internally more homogeneous subgroups, using Kendall's coefficient of concordance W, and show its applicability and application to both simulated and in vivo data. Such group partition and "purification" will help subsequent inferential methods to deal more efficiently with false positives.

Algorithms↗

Novelty indices: identifiers of potentially interesting time-courses in functional MRI data.

In a systematic study of hybrid MR time-series with simulated "activation" (contrast-to-noise range 1-10) we investigated the power and compared the ability of the "novelty indices" (NI) kurtosis, negentropy, and 1-lag autocorrelation, to discriminate between potentially interesting ("structured") and uninteresting ("noisy") time-courses (TCs). NIs may be employed as preprocessing tools to focus only on the interesting TCs prior to any further exploratory or confirmatory approach.

Humans↗

Comparison of two exploratory data analysis methods for fMRI: fuzzy clustering vs. principal component analysis.

Exploratory data-driven methods such as Fuzzy clustering analysis (FCA) and Principal component analysis (PCA) may be considered as hypothesis-generating procedures that are complementary to the hypothesis-led statistical inferential methods in functional magnetic resonance imaging (fMRI). Here, a comparison between FCA and PCA is presented in a systematic fMRI study, with MR data acquired under the null condition, i.e., no activation, with different noise contributions and simulated, varying "activation." The contrast-to-noise (CNR) ratio ranged between 1-10. We found that if fMRI data are corrupted by scanner noise only, FCA and PCA show comparable performance. In the presence of other sources of signal variation (e.g., physiological noise), FCA outperforms PCA in the entire CNR range of interest in fMRI, particularly for low CNR values. The comparison method that we introduced may be used to assess other exploratory approaches such as independent component analysis or neural network-based techniques.

Brain↗

Dual surface coil with high-B1 homogeneity for deep organ MR imaging.

The theory and construction of a dual surface coil which provides good B1 homogeneity and sensitivity in a defined volume of interest is described. The probe comprises two coaxial rings, of different diameters and in different planes, which carry opposing currents of different values. Current in the second ring compensates for the roll-off of the B1 field associated with a single surface coil. Coupling between the rings and a third matching ring is by mutual inductance only. A comparison to a traditional surface coil with practical application to pig brain imaging at a field strength of 7 Tesla is shown.

Animals↗

Cerebral protection during moderate hypothermic circulatory arrest: histopathology and magnetic resonance spectroscopy of brain energetics and intracellular pH in pigs.

OBJECTIVE: We evaluated the effect of antegrade and retrograde brain perfusion during moderate hypothermic circulatory arrest at 28 degrees C. METHODS: Phosphorus 31-magnetic resonance spectroscopy was used to follow brain energy metabolites and intracellular pH in pigs during 2 hours of ischemia and 1 hour of reperfusion. Histopathologic analysis of brain tissue fixed at the end of the experimental protocol was performed. Fourteen pigs were divided into two experimental groups subjected to antegrade (n = 6) or retrograde (n = 8) brain perfusion. Anesthesia (n = 8) and hypothermic cardiopulmonary bypass groups (15 degrees C, n = 8) served as control subjects. In the antegrade and retrograde brain perfusion groups, the initial bypass flow rate was 60 to 100 ml x kg(-1) x min(-1). In the antegrade group, the brain was perfused through the carotid arteries at a flow rate of 180 to 210 ml x min(-1) during circulatory arrest at 28 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml x min(-1) during circulatory arrest at 28 degrees C. RESULTS: The intracellular pH was 7.1 +/- 0.1 and 7.2 +/- 0.1 in the anesthesia and hypothermic bypass groups, respectively. Brain intracellular pH and high-energy metabolites (adenosine triphosphate, phosphocreatine) did not change during the course of the 3.5-hour study. In the antegrade group, adenosine triphosphate and intracellular pH were unchanged throughout the protocol. In the retrograde perfusion group, the intracellular pH level decreased to 6.4 +/- 0.1, and adenosine triphosphate and phosphocreatine levels decreased within the first 30 minutes of circulatory arrest and remained at low levels until the end of reperfusion. High-energy phosphates did not return to their initial levels during reperfusion. Histopathologic analysis of nine regions of the brain showed good preservation of cell structure in the anesthesia, hypothermic bypass, and antegrade perfusion groups. The retrograde perfusion group showed changes in all the regions examined. CONCLUSIONS: The study shows that moderate hypothermic circulatory arrest at 28 degrees C with antegrade brain perfusion during circulatory arrest protects the brain but that retrograde cerebral perfusion at 28 degrees C does not protect the brain.

Adenosine Triphosphate↗

RNA sequence containing hexanucleotide AAUAAA directs efficient mRNA polyadenylation in vitro.

To determine whether a specific nucleotide sequence is required to direct polyadenylation of a simian virus 40 early pre-mRNA in a soluble HeLa whole-cell lysate, we constructed a series of rearranged and deleted DNA templates, transcribed them in vitro, and determined whether the resultant RNAs could be polyadenylated when incubated in whole-cell lysate. When a 237-base-pair DNA fragment encoding the 3' end of the simian virus 40 early pre-mRNA was transferred to recombinant plasmids encoding RNAs that were not substrates for polyadenylation, the resultant RNAs could now be polyadenylated efficiently. In one case, the chimeric RNA was polyadenylated even more efficiently than was the original simian virus 40 early transcript. Analysis of the RNAs produced from the deletion mutant templates revealed that only RNAs containing at least one copy of the AAUAAA sequence situated near the 3' end and implicated in 3'-end formation and polyadenylation in vivo could be polyadenylated in vitro. Surprisingly, this sequence directed polyadenylation of pre-mRNAs not only when near the RNA 3' end, i.e., 50 nucleotides or less away, but also when the 3' end was situated over 400 nucleotides downstream. Thus, our results show that a polyadenylic acid polymerase activity in HeLa lysates can recognize a specific nucleotide sequence in pre-mRNA and then, in the absence of the nucleolytic cleavage that presumably occurs in vivo, locate the RNA 3' end and use it as a primer for polyadenylic acid synthesis.

Base Sequence↗