title: Multiplexed fluorescence tomography with spectral and temporal data: demixing with intrinsic regularization.
abstract: We consider the joint use of spectral and temporal data for multiplexed fluorescence molecular tomography to enable high-throughput imaging of multiple fluorescent targets in bulk tissue. This is a challenging problem due to the narrow near-infrared diagnostic window and relatively broad emission spectra of common fluorophores, and the distortion ("redshift") that the fluorophore signals undergo as they propagate through tissue. We show through a Cramér-Rao lower bound analysis that demixing with spectral-temporal data could result in an order of magnitude improvement in performance over either modality alone. To cope with the resulting large data set, we propose a novel two-stage algorithm that decouples the demixing and tomographic reconstruction operations. In this work we concentrate on the demixing stage. We introduce an approach which incorporates ideas from sparse subspace clustering and compressed sensing and does not require a regularization parameter. We report on simulations in which we simultaneously demixed four fluorophores with closely overlapping spectral and temporal profiles in a 25 mm diameter cross-sectional area with a root-mean-square error of less than 3% per fluorophore, as well as on studies of sensitivity of the method to model mismatch.
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University Boston, MA 02115 USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Pera
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University Boston, MA 02115 USA.
authors.forename: Dana H
authors.initials: DH
authors.lastname: Brooks
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University Boston, MA 02115 USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Niedre
keywords: (170.1580) Chemometrics; (170.3010) Image reconstruction techniques; (170.3660) Light propagation in tissues; (170.3880) Medical and biological imaging; (170.6920) Time-resolved imaging; (170.6960) Tomography
references.citation: J Biomed Opt. 2010 Jul-Aug;15(4):046011
references.pmid: 20799813
references.citation: IEEE Trans Med Imaging. 1999 Mar;18(3):262-71
references.pmid: 10363704
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19126-31
references.pmid: 19015534
references.citation: J Biomed Opt. 2012 Jun;17(6):061202
references.pmid: 22734732
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12294-9
references.pmid: 15304657
references.citation: Nat Med. 2002 Jul;8(7):757-60
references.pmid: 12091907
references.citation: Appl Opt. 2005 Apr 1;44(10):1934-41
references.pmid: 15813529
references.citation: Opt Express. 2008 Aug 18;16(17):13104-21
references.pmid: 18711549
references.citation: Opt Lett. 2014 Mar 1;39(5):1165-8
references.pmid: 24690697
references.citation: J Biomed Opt. 2014 Feb;19(2):025002
references.pmid: 24503635
references.citation: Opt Express. 2007 Dec 10;15(25):16400-12
references.pmid: 19550930
references.citation: Biomed Opt Express. 2011 Feb 23;2(3):665-79
references.pmid: 21412471
references.citation: IEEE Trans Pattern Anal Mach Intell. 2013 Nov;35(11):2765-81
references.pmid: 24051734
references.citation: Opt Lett. 2015 Feb 1;40(3):431-4
references.pmid: 25680065
references.citation: IEEE Trans Med Imaging. 2005 Oct;24(10):1377-86
references.pmid: 16229423
references.citation: Biomed Opt Express. 2011 Mar 14;2(4):871-86
references.pmid: 21483610
references.citation: Biomed Opt Express. 2012 Sep 1;3(9):2036-49
references.pmid: 23024899
references.citation: Phys Med Biol. 2005 Sep 7;50(17):4225-41
references.pmid: 16177541
references.citation: Phys Med Biol. 2014 Jan 6;59(1):R1-64
references.pmid: 24334634
references.citation: Opt Lett. 2012 Jul 1;37(13):2559-61
references.pmid: 22743454