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PubMed2004

Gradients of dopamine D1- and D2/3-binding sites in the basal ganglia of pig and monkey measured by PET.

The distributions of dopamine D1 and D2/3 binding sites in living brain have not been compared directly using positron emission tomography (PET). To map these binding sites, we first optimized methods for the assay of dopamine receptors in brain of Göttingen miniature pigs. The binding potentials (pB) of [11C]NNC 112 for dopamine D1 receptors and [11C]raclopride for dopamine D2/3 receptors were calculated in pig striatum volumes of interest using metabolite corrected arterial inputs or using cerebellum as a non-binding reference region. Depending upon the method for quantitation, the pB for [11C]NNC 112 was 1.2-5.1 in pig striatum, whereas the pB for [11C]raclopride was 1.0-1.8. We used the reference tissue method of Logan to calculate pB maps for the two tracers. The maps were co-registered to the common stereotaxic space for the pig brain and normalized to a global mean for pB in striatum; t-maps showed that dopamine D1 binding was relatively more abundant in the ventral-anterior striatum of the pig, while dopamine D2/3 binding was greater in the dorsal striatum. Similar comparisons were made for the pBs of [11C]Sch 23390 for dopamine D1 receptors and for [11C]raclopride in the brain of six rhesus monkeys. The magnitudes of pB for both binding sites in monkey brain were close to those in the pig. Consistent with the pig results, there were distinct gradients in the distributions of the two binding sites in monkey brain: D1 binding predominated in the ventral striatum, whereas D2/3 binding was relatively greater in the dorsal-posterior striatum. Gradients of dopamine receptor concentration within the striatum may be a general phenomenon of mammalian brain.

Animals↗

PubMed2000

Whole-brain functional MR imaging activation from a finger-tapping task examined with independent component analysis.

BACKGROUND AND PURPOSE: Independent component analysis (ICA), unlike other methods for processing functional MR (fMR) imaging data, requires no a priori assumptions about the hemodynamic response to the task. The purpose of this study was to analyze the temporal characteristics and the spatial mapping of the independent components identified by ICA when the subject performs a finger-tapping task. METHODS: Ten healthy subjects performed variations of the finger-tapping task conventionally used to map the sensorimotor cortex. The scan data were processed with ICA, and the temporal configuration of the components and their spatial localizations were studied. The locations with activation were tabulated and compared with locations known to be involved in the organization of motor functions in the brain. RESULTS: Components were identified that correlated to varying degrees with the conventional boxcar reference function. One or more of these components mapped to the sensorimotor cortex, supplementary motor area (SMA), putamen, and thalamus. By means of ICA components, sensorimotor cortex, supplementary motor area, and superior cerebellar activation were identified bilaterally in 100% of the subjects; thalamus activation was contralateral to the active hand in 80%; and putamen activation was contralateral to the active hand in 60%. CONCLUSION: ICA processing of multislice fMR imaging data acquired during finger tapping identifies the sensorimotor cortex, SMA, cerebellar, putamen, and thalamic activation. ICA appears to be a method that provides information on both the temporal and spatial characteristics of activation. Multiple task-related components can be identified by ICA, and specific activation maps can be derived from each separate component.

Brain↗

PubMed1994

Genome structure and evolution in Drosophila: applications of the framework P1 map.

Physical maps showing the relative locations of cloned DNA fragments in the genome are important resources for research in molecular genetics, genome analysis, and evolutionary biology. In addition to affording a common frame of reference for organizing diverse types of genetic data, physical maps also provide ready access to clones containing DNA sequences from any defined region of the genome. In this paper, we present a physical map of the genome of Drosophila melanogaster based on in situ hybridization with 2461 DNA fragments, averaging approximately 80 kilobase pairs each, cloned in bacteriophage P1. The map is a framework map in the sense that most putative overlaps between clones have not yet been demonstrated at the molecular level. Nevertheless, the framework map includes approximately 85% of all genes in the euchromatic genome. A continuous physical map composed of sets of overlapping P1 clones (contigs), which together span most of the euchromatic genome, is currently being assembled by screening a library of 9216 P1 clones with single-copy genetic markers as well as with the ends of the P1 clones already assigned positions in the framework map. Because most P1 clones from D. melanogaster hybridize in situ with chromosomes from related species, the framework map also makes it possible to determine the genome maps of D. pseudoobscura and other species in the subgenus Sophophora. Likewise, a P1 framework map of D. virilis affords potential access to genome organization and evolution in the subgenus Drosophila.

Animals↗

PubMed2000

Functional magnetic resonance imaging in real time (FIRE): sliding-window correlation analysis and reference-vector optimization.

New algorithms for correlation analysis are presented that allow the mapping of brain activity from functional MRI (fMRI) data in real time during the ongoing scan. They combine the computation of the correlation coefficients between measured fMRI time-series data and a reference vector with "detrending", a technique for the suppression of non-stimulus-related signal components, and the "sliding-window technique". Using this technique, which limits the correlation computation to the last N measurement time points, the sensitivity to changes in brain activity is maintained throughout the whole experiment. For increased sensitivity in activation detection a fast and robust optimization of the reference vector is proposed, which takes into account a realistic model of the hemodynamic response function to adapt the parameterized reference vector to the measured data. Based on the described correlation method, real-time fMRI experiments using visual stimulation paradigms have been performed successfully on a clinical MR scanner, which was linked to an external workstation for image analysis.

Adult↗

PubMed1988

Mapping techniques for document processing.

An information retrieval system should provide references to the set of documents the user must evaluate in order to satisfy his/her information requirements. A major concern in this evaluation process is whether or not a document meets the user's needs. In many document retrieval systems there is no relevant information regarding the content of the documents. This makes it very difficult to evaluate if a document is relevant to the user's initial query. This suggests the need for a method to compare the documents on a word by word basis. Fully automated methods are too complex and difficult to generalize upon. A semiautomated user driven method for document mapping is described in this paper. It should decrease the amount of time required to validate the information content of a query.

Documentation↗

PubMed2004

Mapping high-dimensional data onto a relative distance plane--an exact method for visualizing and characterizing high-dimensional patterns.

We introduce a distance (similarity)-based mapping for the visualization of high-dimensional patterns and their relative relationships. The mapping preserves exactly the original distances between points with respect to any two reference patterns in a special two-dimensional coordinate system, the relative distance plane (RDP). As only a single calculation of a distance matrix is required, this method is computationally efficient, an essential requirement for any exploratory data analysis. The data visualization afforded by this representation permits a rapid assessment of class pattern distributions. In particular, we can determine with a simple statistical test whether both training and validation sets of a 2-class, high-dimensional dataset derive from the same class distributions. We can explore any dataset in detail by identifying the subset of reference pairs whose members belong to different classes, cycling through this subset, and for each pair, mapping the remaining patterns. These multiple viewpoints facilitate the identification and confirmation of outliers. We demonstrate the effectiveness of this method on several complex biomedical datasets. Because of its efficiency, effectiveness, and versatility, one may use the RDP representation as an initial, data mining exploration that precedes classification by some classifier. Once final enhancements to the RDP mapping software are completed, we plan to make it freely available to researchers.

Algorithms↗

PubMed2001

Molecular interaction maps as information organizers and simulation guides.

A graphical method for mapping bioregulatory networks is presented that is suited for the representation of multimolecular complexes, protein modifications, as well as actions at cell membranes and between protein domains. The symbol conventions defined for these molecular interaction maps are designed to accommodate multiprotein assemblies and protein modifications that can generate combinatorially large numbers of molecular species. Diagrams can either be "heuristic," meaning that detailed knowledge of all possible reaction paths is not required, or "explicit," meaning that the diagrams are totally unambiguous and suitable for simulation. Interaction maps are linked to annotation lists and indexes that provide ready access to pertinent data and references, and that allow any molecular species to be easily located. Illustrative interaction maps are included on the domain interactions of Src, transcription control of E2F-regulated genes, and signaling from receptor tyrosine kinase through phosphoinositides to Akt/PKB. A simple method of going from an explicit interaction diagram to an input file for a simulation program is outlined, in which the differential equations need not be written out. The role of interaction maps in selecting and defining systems for modeling is discussed. (c) 2001 American Institute of Physics.

Journal Article↗

PubMed1992

Genetic mapping of four dinucleotide repeat loci, DXS453, DXS458, DXS454, and DXS424, on the X chromosome using multiplex polymerase chain reaction.

Dinucleotide CA repeat sequences in the human genome have been shown to be highly polymorphic due to variation in the length of the repeat-containing segment. Therefore, these markers can serve as anchor loci in the construction of a high-resolution genetic map of the human genome. In this study, we improved the efficiency of typing dinucleotide repeats using multiplex polymerase chain reaction (PCR). Dinucleotide repeat sequences of four previously identified markers (DXS453, DXS458, DXS454, and DXS424) on the long arm of the X chromosome were simultaneously amplified in a single PCR reaction. This multiplex PCR was applied to genotype individuals from the 40 CEPH reference families, and the genotypic data were used to determine the map position of the four loci with respect to eight reference markers in the Xq region by linkage analysis.

Base Sequence↗

PubMed2001

Investigation of arsenic speciation in oyster test reference material by multidimensional HPLC-ICP-MS and electrospray tandem mass spectrometry (ES-MS-MS).

Multidimensional (size-exclusion-anion-exchange-cation-exchange) liquid chromatography with ICP-MS detection was developed to produce a map of water-soluble species in an oyster test reference material. The presence of arsenobetaine, trimethyl(2-carboxyethyl)arsonium inner salt, arsenocholine, dimethylarsonic acid, tetramethylammonium ion, As(v) and two arsenosugars was demonstrated by ES-MS-MS. A previously unreported compound was isolated and identified by ES-MS-MS as 5-dimethylarsinoyl-beta-ribofuranose. Anion-exchange chromatography was optimized to produce a chromatographically pure peak of arsenobetaine (accounting for ca. 64% of all water-soluble As present) that was used to quantify this compound.

Animals↗

PubMed1998

Body surface mapping of atrial arrhythmias: atlas of paced P wave integral maps to localize the focal origin of right atrial tachycardia.

Successful curative treatment of right atrial tachycardia (AT) can be obtained provided detailed catheter activation mapping of the target site for radiofrequency energy application has been accomplished. However, right AT mapping may be difficult with a single roving catheter due to infrequent presence or noninducibility of the arrhythmia. The present report describes the preliminary clinical use of body surface mapping as an adjunctive noninvasive method to identify the region of AT origin prior to catheter ablation. This technique has been previously applied to develop a reference data base of 17 different paced P wave integral map patterns. The data base was designed by performing right atrial pace mapping in patients without structural heart disease. Each P wave integral map pattern in the data base is unique to ectopic activation onset in a circumscribed right atrial endocardial segment. Localization of the segment of AT origin is accomplished by matching the P wave integral map of a single AT beat with the data base of paced P wave integral maps. The use of body surface mapping as an integral part of the mapping protocol during radiofrequency catheter ablation of right AT offers the possibility to: (1) noninvasively determine the arrhythmogenic target area for ablation using a single beat analysis approach; (2) confine detailed catheter activation mapping to a limited area; and (3) accelerate the overall procedure and limit fluoroscopic exposure by reducing the time required for mapping.

Body Surface Potential Mapping↗

PubMed1991

A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates.

Utilizing the CEPH reference panel and genotypic data for 53 markers, we have constructed a 20-locus multipoint genetic map of human chromosome 4. New RFLPs are reported for four loci. The map integrates a high-resolution genetic map of 4p16 into a continuous map extending to 4q31 and an unlinked cluster of three loci at 4q35. The 20 linked markers form a continuous linkage group of 152 cM in males and 202 cM in females. Likely genetic locations are provided for 25 polymorphic anonymous sequences and 28 gene-specific RFLPs. The map was constructed employing the LINKAGE and CRIMAP computational methodologies to build the multipoint map via a stepwise algorithm. A detailed 10-point map of the 4p16 region constructed from the CEPH panel provides evidence for heterogeneity in the linkage maps constructed from families segregating for Huntington disease (HD). It additionally provides evidence for position-specific recombination frequencies in the telomeric region of 4p.

Chromosome Mapping↗

PubMed1969

The general theory of mapping functions for random genetic recombination.

The general theory of mapping functions for random genetic recombination is derived without reference to physical models. The results are of particular relevance to asymmetric recombination (preferential recombination of the alleles of either parent) and include the effects of lethal lesions. It is noted that the assumption of randomness determines the mapping functions uniquely so that they are independent of the specifications of any stochastic physical model of recombination. In particular, the functions derived from physical models by Haldane, Wu, Wood and Verhoef and de Haan are special cases of those derived here. A general principle for the testing of genetic linkage is formulated which is valid for both symmetric and asymmetric recombination.

Chromosome Mapping↗

PubMed2005

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes.

PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

Algorithms↗

PubMedDate not supplied

Informatics in Radiology (infoRAD): Magnetic Resonance Imaging Workbench: analysis and visualization of dynamic contrast-enhanced MR imaging data.

Magnetic Resonance Imaging Workbench (MRIW) allows analysis of T1- and T2*-weighted dynamic contrast-enhanced magnetic resonance imaging data sets to extract tissue permeability and perfusion characteristics by using standard pharmacokinetic models. Parametric maps are calculated from individual pixel enhancement curves in regions of interest (ROIs) and displayed as color overlays on the anatomic images. User-defined ROIs can be saved to ensure consistency of later reanalysis. Individual parametric maps are visualized together with user-selected parameter time-series plots. The following selections are available: overall ROI enhancement curve and fit, histogram, and individual pixel enhancement curve and fit. Summary data (transfer constant, leakage space, rate constant, integrated area under the gadolinium curve after 60 seconds, relative blood volume, relative blood flow, and mean transit time) may be exported to permanent storage along with per-pixel results for statistical analysis. Numerical values for parameters are displayed below the plot for easy reference. The dynamic range of plots and parametric map overlays is interactively adjustable. Viewing individual enhancement curves and parametric maps allows radiologists to investigate the heterogeneity of contrast agent kinetics for lesion characterization and to scrutinize serial changes in response to therapy. MRIW is written in IDL, enabling it to be used on a variety of computer systems.

Computer Graphics↗

PubMed1993

A linkage map of human chromosome 15 with an average resolution of 2 cM and containing 55 polymorphic microsatellites.

We have constructed a 2.0 centiMorgan (cM) resolution genetic linkage map for chromosome 15q that contains 55 polymorphic satellites and 3 RFLPs that have placed on the map with odds for order of at least 1,000:1. Genotypes from 67 polymorphic loci (64 polymorphic microsatellites) were used to construct the map. Nine genes are included in the 1,000:1 map and 37 markers have heterozygosities of at least 70%. The sex-equal map length is 128 cM and the largest genetic interval is 11 cM (15.5 cM on the female map). The female and male map lengths are 150 cM and 106 cM, respectively. The map was constructed with 'MultiMap' and is based on the CEPH reference pedigrees and includes over 12,000 new genotypes. A sub-set of 12 markers spanning the length of the linkage map were genotyped in a somatic cell hybrid panel with breakpoints that divided 15q into five segments. Cytogenetic placement agreed with the linkage positions for each of the microsatellites tested with the exception of one (ACTC) which failed to give consistent results. Ten spontaneous new mutations were identified from a subset of 42 polymorphic microsatellites (out of a total of 20,420 transmissions), giving an apparent observed spontaneous mutation rate of 5 x 10(-4) per locus. An integrated map of chromosome 15q was also constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. The sex average map spans 144.7 cM with an average distance between unique map locations of 3.5 cM and a maximum intermarker distance of 11.5 cM. These genetic linkage maps can be considered baseline maps for 15q which will be useful for physical mapping and the localization of disease genes and other genes of interest.

Base Sequence↗

PubMed2000

An SNP map of human chromosome 22.

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.

Cell Line↗

PubMed2004

Improved localization of right-sided accessory pathways with microcatheter-assisted right coronary artery mapping in children.

INTRODUCTION: Radiofrequency ablation of some right-sided accessory pathways continues to be challenging. The purpose of this study was to evaluate the efficacy of introducing a multielectrode microcatheter in the right coronary artery to localize accessory pathways when conventional mapping was unsuccessful. METHODS AND RESULTS: A retrospective study was conducted of all right-sided accessory pathway radiofrequency ablation procedures in which a multielectrode microcatheter as a reference in the right coronary artery was used to assist mapping. Between January 1998 and January 2002, 10 patients (5 males) underwent mapping of 11 accessory pathways with this technique at mean age of 12.3 +/- 3.8 years. Five patients had Ebstein's anomaly of the tricuspid valve. Accessory pathways were identified in the following locations: right anterior 3, right anterolateral 2, right lateral 1, right posterolateral 2, and right posterior 3. Mean procedure time was 285 +/- 70.3 minutes, and fluoroscopy time was 68.7 +/- 21 minutes. Average mapping duration prior to microcatheter insertion in the right coronary artery was 136 +/- 40 minutes. After microcatheter placement in the right coronary artery, the time to successful ablation of accessory pathways was 38 +/- 11 minutes. All 11 (100%) accessory pathways were successfully ablated. CONCLUSION: Mapping in the right coronary artery with a microcatheter is an effective method to improve localization and successful ablation of difficult right-sided accessory pathways.

Adolescent↗

PubMed1993

The goals and status of the bovine gene map.

The bovine genome map has developed rapidly in recent years. The synteny and chromosomal maps are sufficiently developed to identify chromosomal conservation with other mammals, which is especially useful for the extrapolation of data to cattle from the better developed maps of mouse and human. The rapid development of microsatellite and other hypervariable markers in several laboratories around the world and the availability of a common set of reference families for linkage analysis will produce a 20-cM map in 2 yr. Immediate needs for development are 1) markers to anchor physical maps to linkage maps, 2) resource families segregating economic trait loci, and 3) chromosome-specific libraries to develop densely saturated linkage maps over genomic regions shown to contain economic trait loci.

Animals↗