{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hou SS"],"funding":["NIBIB NIH HHS","NCI NIH HHS","National Institutes of Health"],"pagination":["2341-2351"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6659996"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["66(8)"],"pubmed_abstract":["<h4>Objective</h4>We use a resolution matrix-based Bayesian framework to compare inversion methods for tomographic fluorescence lifetime multiplexing in a diffuse medium, such as biological tissue.<h4>Methods</h4>We consider three inversion methods; an asymptotic time domain (ATD) approach, based on a multiexponential analysis of time domain data, a direct time domain (DTD) approach, which is a minimum error solution, and a cross-talk constrained time domain (CCTD) inversion, which is a solution to an optimization problem that minimizes both error and cross-talk. We compare these methods using Monte Carlo simulations and time domain fluorescence measurements with tissue-mimicking phantoms.<h4>Results</h4>The ATD approach provides high accuracy of relative quantitation and spatial localization of two fluorophores embedded in a 18-mm thick turbid medium, with concentration ratios of up to 1:4.25. DTD leads to significant errors in relative quantitation and localization. CCTD provides improved quantitation accuracy over DTD, and better spatial resolution compared to ATD. We present a rigorous theoretical basis for these results and provide a complete derivation of the CCTD estimator. The Bayesian analysis also leads to a formula for rapid computation of the DTD inverse operator for large-scale tomography measurements.<h4>Conclusion</h4>The ATD and CCTD inversion methods provide significant advantages over DTD for accurately estimating multiple overlapping fluorophores.<h4>Significance</h4>Time domain fluorescence tomography, using zero cross-talk estimators, can serve as a powerful tool for quantifying multiple fluorescently labeled biological processes. The Bayesian framework presented here can be applied to general multiparameter inverse problems for the quantitative estimation of multiple overlapping parameters."],"journal":["IEEE transactions on bio-medical engineering"],"pubmed_title":["The Resolution Matrix in Tomographic Multiplexing: Optimization of Inter-Parameter Cross-Talk, Relative Quantitation, and Localization."],"pmcid":["PMC6659996"],"funding_grant_id":["R01 CA211084","R01 EB000768","R01 EB 000768","R01 CA 211084"],"pubmed_authors":["Kumar ATN","Hou SS","Bacskai BJ"],"additional_accession":[]},"is_claimable":false,"name":"The Resolution Matrix in Tomographic Multiplexing: Optimization of Inter-Parameter Cross-Talk, Relative Quantitation, and Localization.","description":"<h4>Objective</h4>We use a resolution matrix-based Bayesian framework to compare inversion methods for tomographic fluorescence lifetime multiplexing in a diffuse medium, such as biological tissue.<h4>Methods</h4>We consider three inversion methods; an asymptotic time domain (ATD) approach, based on a multiexponential analysis of time domain data, a direct time domain (DTD) approach, which is a minimum error solution, and a cross-talk constrained time domain (CCTD) inversion, which is a solution to an optimization problem that minimizes both error and cross-talk. We compare these methods using Monte Carlo simulations and time domain fluorescence measurements with tissue-mimicking phantoms.<h4>Results</h4>The ATD approach provides high accuracy of relative quantitation and spatial localization of two fluorophores embedded in a 18-mm thick turbid medium, with concentration ratios of up to 1:4.25. DTD leads to significant errors in relative quantitation and localization. CCTD provides improved quantitation accuracy over DTD, and better spatial resolution compared to ATD. We present a rigorous theoretical basis for these results and provide a complete derivation of the CCTD estimator. The Bayesian analysis also leads to a formula for rapid computation of the DTD inverse operator for large-scale tomography measurements.<h4>Conclusion</h4>The ATD and CCTD inversion methods provide significant advantages over DTD for accurately estimating multiple overlapping fluorophores.<h4>Significance</h4>Time domain fluorescence tomography, using zero cross-talk estimators, can serve as a powerful tool for quantifying multiple fluorescently labeled biological processes. The Bayesian framework presented here can be applied to general multiparameter inverse problems for the quantitative estimation of multiple overlapping parameters.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-29T10:33:47.508Z","creation":"2020-09-11T07:20:32Z"},"accession":"S-EPMC6659996","cross_references":{"pubmed":["30582520"],"doi":["10.1109/tbme.2018.2889043","10.1109/TBME.2018.2889043"]}}