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Article ; Online: Functional 4-D clustering for characterizing intratumor heterogeneity in dynamic imaging: evaluation in FDG PET as a prognostic biomarker for breast cancer.

Chitalia, Rhea / Viswanath, Varsha / Pantel, Austin R / Peterson, Lanell M / Gastounioti, Aimilia / Cohen, Eric A / Muzi, Mark / Karp, Joel / Mankoff, David A / Kontos, Despina

European journal of nuclear medicine and molecular imaging

2021 Volume 48, Issue 12, Page(s) 3990–4001

Abstract: Purpose: Probe-based dynamic (4-D) imaging modalities capture breast intratumor heterogeneity ... clinical decision making.: Methods: We propose an unsupervised clustering algorithm for 4-D imaging ... intratumor heterogeneity. We applied this to dynamic FDG PET scans by identifying distinct time-activity ...

Abstract	Purpose: Probe-based dynamic (4-D) imaging modalities capture breast intratumor heterogeneity both spatially and kinetically. Characterizing heterogeneity through tumor sub-populations with distinct functional behavior may elucidate tumor biology to improve targeted therapy specificity and enable precision clinical decision making. Methods: We propose an unsupervised clustering algorithm for 4-D imaging that integrates Markov-Random Field (MRF) image segmentation with time-series analysis to characterize kinetic intratumor heterogeneity. We applied this to dynamic FDG PET scans by identifying distinct time-activity curve (TAC) profiles with spatial proximity constraints. We first evaluated algorithm performance using simulated dynamic data. We then applied our algorithm to a dataset of 50 women with locally advanced breast cancer imaged by dynamic FDG PET prior to treatment and followed to monitor for disease recurrence. A functional tumor heterogeneity (FTH) signature was then extracted from functionally distinct sub-regions within each tumor. Cross-validated time-to-event analysis was performed to assess the prognostic value of FTH signatures compared to established histopathological and kinetic prognostic markers. Results: Adding FTH signatures to a baseline model of known predictors of disease recurrence and established FDG PET uptake and kinetic markers improved the concordance statistic (C-statistic) from 0.59 to 0.74 (p = 0.005). Unsupervised hierarchical clustering of the FTH signatures identified two significant (p < 0.001) phenotypes of tumor heterogeneity corresponding to high and low FTH. Distributions of FDG flux, or Ki, were significantly different (p = 0.04) across the two phenotypes. Conclusions: Our findings suggest that imaging markers of FTH add independent value beyond standard PET imaging metrics in predicting recurrence-free survival in breast cancer and thus merit further study.
MeSH term(s)	Biomarkers ; Breast Neoplasms/diagnostic imaging ; Cluster Analysis ; Female ; Fluorodeoxyglucose F18 ; Humans ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Prognosis
Chemical Substances	Biomarkers ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2021-03-07
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-021-05265-8
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Article ; Online: Correction to: Functional 4-D clustering for characterizing intratumor heterogeneity in dynamic imaging: evaluation in FDG PET as a prognostic biomarker for breast cancer.

Chitalia, Rhea / Viswanath, Varsha / Pantel, Austin R / Peterson, Lanell M / Gastounioti, Aimilia / Cohen, Eric A / Muzi, Mark / Karp, Joel / Mankoff, David A / Kontos, Despina

European journal of nuclear medicine and molecular imaging

2021 Volume 48, Issue 12, Page(s) 4109

Language	English
Publishing date	2021-06-09
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-021-05324-0
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Article: The Omics Dashboard for Interactive Exploration of Metabolomics and Multi-Omics Data.

Paley, Suzanne / Karp, Peter D

Metabolites

2024 Volume 14, Issue 1

Abstract: The Omics Dashboard is a software tool for interactive exploration and analysis of metabolomics, transcriptomics, proteomics, and multi-omics datasets. Organized as a hierarchy of cellular systems, the Dashboard at its highest level contains graphical ... ...

Abstract	The Omics Dashboard is a software tool for interactive exploration and analysis of metabolomics, transcriptomics, proteomics, and multi-omics datasets. Organized as a hierarchy of cellular systems, the Dashboard at its highest level contains graphical panels for the full range of cellular systems, including biosynthesis, energy metabolism, and response to stimulus. Thus, the Dashboard top level surveys the state of the cell across a broad range of key systems in a single screen. Each Dashboard panel contains a series of X-Y plots depicting the aggregated omics data values relevant to different subsystems of that panel, e.g., subsystems within the biosynthesis panel include amino acid biosynthesis, carbohydrate biosynthesis and cofactor biosynthesis. Users can interactively drill down to focus in on successively lower-level subsystems of interest. In this article, we present for the first time the metabolomics analysis capabilities of the Omics Dashboard, along with significant new extensions to better accommodate metabolomics datasets, enable analysis and visualization of multi-omics datasets, and provide new data-filtering options.
Language	English
Publishing date	2024-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo14010065
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Article ; Online: Reviewing knowledgebase and database grant proposals in the life sciences: the role of innovation.

Karp, Peter D

Database : the journal of biological databases and curation

2022 Volume 2022

Abstract: This article offers thoughts on reviewing grant proposals for biological knowledgebases and databases (KDs) in the hope of aiding grant reviewers and applicants in addressing the issue of innovation. Assessing such grant proposals involves a number of ... ...

Abstract	This article offers thoughts on reviewing grant proposals for biological knowledgebases and databases (KDs) in the hope of aiding grant reviewers and applicants in addressing the issue of innovation. Assessing such grant proposals involves a number of subtleties that are worthy of discussion, particularly for new reviewers and applicants. In part, this article is motivated by the release of two funding opportunity announcements by the US National Institutes of Health concerning KDs. We find that the amount of innovation required for different KD projects can vary significantly, particularly depending on where in its life cycle a given project is. Strong innovation is not necessarily required to have an impactful KD project. For example, PubMed has low innovation but high impact. The importance of innovation should be weighted differently for different KD projects depending on the challenges they face and their maturity. The score for the overall impact of a grant proposal might have little dependence on the innovation score, such as for a mature project that is already delivering strong impact.
MeSH term(s)	United States ; Financing, Organized ; National Institutes of Health (U.S.) ; Biological Science Disciplines ; Knowledge Bases
Language	English
Publishing date	2022-12-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/baac106
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Article: Investigation of time-of-flight benefit for fully 3-D PET.

Surti, Suleman / Karp, Joel S / Popescu, Lucretiu M / Daube-Witherspoon, Margaret E / Werner, Matthew

IEEE transactions on medical imaging

2006 Volume 25, Issue 5, Page(s) 529–538

Abstract: ... for a time-of-flight (TOF) fully three-dimensional (3-D) whole-body positron emission tomography (PET ... scanner. We simulate a 3-D whole-body time-of-flight PET scanner with a complete modeling of spatial and ...

Abstract	The purpose of this paper is to determine the benefit that can be achieved in image quality for a time-of-flight (TOF) fully three-dimensional (3-D) whole-body positron emission tomography (PET) scanner. We simulate a 3-D whole-body time-of-flight PET scanner with a complete modeling of spatial and energy resolutions. The scanner is based on LaBr3 Anger-logic detectors with which 300ps timing resolution has been achieved. Multiple simulations were performed for 70-cm long uniform cylinders with 27-cm and 35-cm diameters, containing hot spheres (22, 17, 13, and 10-mm diameter) in a central slice and 10-mm diameter hot spheres in a slice at 1/4 axial FOV. Image reconstruction was performed with a list-mode iterative TOF algorithm and data were analyzed after attenuation and scatter corrections for timing resolutions of 300, 600, 1000 ps and non-TOF for varying count levels. The results show that contrast recovery improves slightly with TOF (NEMA NU2-2001 analysis), and improved timing resolution leads to a faster convergence to the maximum contrast value. Detectability for 10-mm diameter hot spheres estimated using a nonprewhitening matched filter (NPW SNR) also improves nonlinearly with TOF. The gain in image quality using contrast and noise measures is proportional to the object diameter and inversely proportional to the timing resolution of the scanner. The gains in NPW SNR are smaller, but they also increase with increasing object diameter and improved timing resolution. The results show that scan times can be reduced in a TOF scanner to achieve images similar to those from a non-TOF scanner, or improved image quality achieved for same scan times.
MeSH term(s)	Algorithms ; Computer Simulation ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Information Storage and Retrieval/methods ; Models, Biological ; Phantoms, Imaging ; Positron-Emission Tomography/instrumentation ; Positron-Emission Tomography/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Whole Body Imaging/methods
Language	English
Publishing date	2006-05
Publishing country	United States
Document type	Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2006.871419
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Article: Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner.

Chiang, Stephen / Cardi, Chris / Matej, Samuel / Zhuang, Hongming / Newberg, Andrew / Alavi, Abass / Karp, Joel S

Nuclear medicine communications

2004 Volume 25, Issue 11, Page(s) 1103–1107

Abstract: ... utilize PET data acquired in true 3-D acquisition modes, as compared to 2-D approaches involving data ... involving simulated and real phantom data from PET scanners working purely in 3-D acquisition mode, showed ... Introduction: Fully three-dimensional (3-D) reconstruction algorithms have the potential to better ...

Abstract	Introduction: Fully three-dimensional (3-D) reconstruction algorithms have the potential to better utilize PET data acquired in true 3-D acquisition modes, as compared to 2-D approaches involving data reduction through rebinning procedures followed by a 2-D or 2.5-D reconstruction. Our previous studies, involving simulated and real phantom data from PET scanners working purely in 3-D acquisition mode, showed that the fully 3-D reconstruction approaches bring appreciable improvement on physical measures and visual image quality as well. Reconstruction procedures utilized in those studies were based upon the row action maximum likelihood algorithm (RAMLA) implemented on our clinical scanners. The purpose of this study was to investigate if the fully 3-D RAMLA reconstruction software brings an appreciable improvement in clinical image quality and reader confidence. Materials and methods: Ninety patient scans acquired on the Philips CPET scanner at our institution were reconstructed using 2.5-D RAMLA and 3-D RAMLA with differing reconstruction parameters. These scans were blindly presented to four experienced PET scan readers who graded various aspects of image quality. Results: Our study concluded that 3-D RAMLA on the CPET scanner reduces artifacts and image noise and improves clinical confidence in interpreting PET images. Conclusion: This study led to the routine use of 3-D RAMLA reconstruction on the CPET scanner at our institution.
MeSH term(s)	Algorithms ; Artifacts ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Likelihood Functions ; Phantoms, Imaging ; Positron-Emission Tomography/instrumentation ; Positron-Emission Tomography/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Single-Blind Method ; Subtraction Technique
Language	English
Publishing date	2004-09-03
Publishing country	England
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Validation Studies
ZDB-ID	758141-5
ISSN	1473-5628 ; 0143-3636
ISSN (online)	1473-5628
ISSN	0143-3636
DOI	10.1097/00006231-200411000-00006
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Article ; Online: Efficient 3-D TOF PET reconstruction using view-grouped histo-images: DIRECT-direct image reconstruction for TOF.

Matej, Samuel / Surti, Suleman / Jayanthi, Shridhar / Daube-Witherspoon, Margaret E / Lewitt, Robert M / Karp, Joel S

IEEE transactions on medical imaging

2009 Volume 28, Issue 5, Page(s) 739–751

Abstract: For modern time-of-flight (TOF) positron emission tomography (PET) systems, in which the number ...

Abstract	For modern time-of-flight (TOF) positron emission tomography (PET) systems, in which the number of possible lines of response and TOF bins is much larger than the number of acquired events, the most appropriate reconstruction approaches are considered to be list-mode methods. However, their shortcomings are relatively high computational costs for reconstruction and for sensitivity matrix calculation. Efficient treatment of TOF data within the proposed DIRECT approach is obtained by 1) angular (azimuthal and co-polar) grouping of TOF events to a set of views as given by the angular sampling requirements for the TOF resolution, and 2) deposition (weighted-histogramming) of these grouped events, and correction data, into a set of "histo-images," one histo-image per view. The histo-images have the same geometry (voxel grid, size and orientation) as the reconstructed image. The concept is similar to the approach involving binning of the TOF data into angularly subsampled histo-projections-projections expanded in the TOF directions. However, unlike binning into histo-projections, the deposition of TOF events directly into the image voxels eliminates the need for tracing and/or interpolation operations during the reconstruction. Together with the performance of reconstruction operations directly in image space, this leads to a very efficient implementation of TOF reconstruction algorithms. Furthermore, the resolution properties are not compromised either, since events are placed into the image elements of the desired size from the beginning. Concepts and efficiency of the proposed data partitioning scheme are demonstrated in this work by using the DIRECT approach in conjunction with the row-action maximum-likelihood (RAMLA) algorithm.
MeSH term(s)	Algorithms ; Computer Simulation ; Fourier Analysis ; Image Processing, Computer-Assisted/methods ; Monte Carlo Method ; Phantoms, Imaging ; Positron-Emission Tomography
Language	English
Publishing date	2009-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2008.2012034
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Article ; Online: The BioCyc Metabolic Network Explorer.

Paley, Suzanne / Karp, Peter D

BMC bioinformatics

2021 Volume 22, Issue 1, Page(s) 208

Abstract: Background: The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show ... ...

Abstract	Background: The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show only a subset of all possible metabolite connections, or the results will be visually overwhelming. Existing tools, even those that purport to show an organism's full metabolic network, limit the set of displayed connections based on predefined pathways or other preselected criteria. We sought instead to provide a tool that would give the user dynamic control over which connections to follow. Results: The Metabolic Network Explorer is an easy-to-use, web-based software tool that allows the user to specify a starting metabolite of interest and interactively explore its immediate metabolic neighborhood in either or both directions to any desired depth, letting the user select from the full set of connected reactions. Although, as for other tools, only a small portion of the metabolic network is visible at a time, that portion is selected by the user, based on the full reaction complement, and it is easy to switch among alternate paths of interest. The display is intuitive, customizable, and provides copious links to more detailed information pages. Conclusions: The Metabolic Network Explorer fills a gap in the set of metabolic network visualization tools and complements other modes of exploration. Its primary strengths are its ease of use, diagrams that are intuitive to biologists, and its integration with the broader corpus of data provided by a BioCyc Pathway/Genome Database.
MeSH term(s)	Internet ; Metabolic Networks and Pathways ; Software
Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-021-04132-5
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Book ; Online: A Comparison of the Pathway Tools Software with the Reactome Software

Karp, Peter D.

2020

Abstract: This document compares SRI's Pathway Tools (PTools) software with the Reactome software. Both software systems serve the pathway bioinformatics area, including representation and analysis of metabolic pathways and signaling pathways. The comparison ... ...

Abstract	This document compares SRI's Pathway Tools (PTools) software with the Reactome software. Both software systems serve the pathway bioinformatics area, including representation and analysis of metabolic pathways and signaling pathways. The comparison covers pathway bioinformatics capabilities, but does not cover other major facets of Pathway Tools that are completely absent from the Reactome software: Pathway Tools genome-informatics capabilities, regulatory informatics capabilities, and table-based analysis tools (SmartTables). Our overall findings are as follows. (1) PTools is significantly ahead of Reactome in its basic information pages. For example, PTools pathway layout algorithms have been developed to an advanced state over several decades, whereas Reactome pathway layouts are illegible, omit important information, and are created manually and therefore cannot scale to thousands of genomes. (2) PTools is far ahead of Reactome in omics analysis. PTools includes all of the omics-analysis methods that Reactome provides, and includes multiple methods that Reactome lacks. (3) PTools contains a metabolic route search tool (searching for paths through the metabolic network), which Reactome lacks. (4) PTools is significantly ahead of Reactome in inference of metabolic pathways from genome information to create new metabolic databases. (5) PTools has an extensive complement of metabolic-modeling tools whereas Reactome has none. (6) PTools is more scalable than Reactome, handling 18,000 genomes versus 90 genomes for Reactome. (7) PTools has a larger user base than Reactome. PTools powers 17 websites versus two for Reactome. PTools has been licensed by 10,800 users (Reactome licensed user count is unknown).
Keywords	Quantitative Biology - Molecular Networks
Subject code	004
Publishing date	2020-09-28
Publishing country	us
Document type	Book ; Online
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Article ; Online: The BioCyc Metabolic Network Explorer

Suzanne Paley / Peter D. Karp

BMC Bioinformatics, Vol 22, Iss 1, Pp 1-

2021 Volume 6

Abstract: Abstract Background The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by ... ...

Abstract	Abstract Background The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show only a subset of all possible metabolite connections, or the results will be visually overwhelming. Existing tools, even those that purport to show an organism’s full metabolic network, limit the set of displayed connections based on predefined pathways or other preselected criteria. We sought instead to provide a tool that would give the user dynamic control over which connections to follow. Results The Metabolic Network Explorer is an easy-to-use, web-based software tool that allows the user to specify a starting metabolite of interest and interactively explore its immediate metabolic neighborhood in either or both directions to any desired depth, letting the user select from the full set of connected reactions. Although, as for other tools, only a small portion of the metabolic network is visible at a time, that portion is selected by the user, based on the full reaction complement, and it is easy to switch among alternate paths of interest. The display is intuitive, customizable, and provides copious links to more detailed information pages. Conclusions The Metabolic Network Explorer fills a gap in the set of metabolic network visualization tools and complements other modes of exploration. Its primary strengths are its ease of use, diagrams that are intuitive to biologists, and its integration with the broader corpus of data provided by a BioCyc Pathway/Genome Database.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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