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  1. Article: Comparison of fluorescence lifetime and multispectral imaging for quantitative multiplexing in biological tissue.

    Pal, Rahul / Kumar, Anand T N

    Biomedical optics express

    2022  Volume 13, Issue 7, Page(s) 3854–3868

    Abstract: Fluorescence lifetime (FLT) multiplexing and multispectral imaging (MSI) are both frequently employed ... ...

    Abstract Fluorescence lifetime (FLT) multiplexing and multispectral imaging (MSI) are both frequently employed for
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2572216-5
    ISSN 2156-7085
    ISSN 2156-7085
    DOI 10.1364/BOE.459935
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Erratum: Comparison of fluorescence lifetime and multispectral imaging for quantitative multiplexing in biological tissue: erratum.

    Pal, Rahul / Kumar, Anand T N

    Biomedical optics express

    2022  Volume 13, Issue 11, Page(s) 5738–5739

    Abstract: This corrects the article on p. 3854 in vol. 13, PMID: 35991924.]. ...

    Abstract [This corrects the article on p. 3854 in vol. 13, PMID: 35991924.].
    Language English
    Publishing date 2022-10-11
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2572216-5
    ISSN 2156-7085
    ISSN 2156-7085
    DOI 10.1364/BOE.476976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Propagation of time-resolved fluorescence in a diffuse medium: complex analytical derivation.

    Kumar, Anand T N

    Journal of the Optical Society of America. A, Optics, image science, and vision

    2020  Volume 37, Issue 5, Page(s) 859–864

    Abstract: The spatiotemporal evolution of fluorescence in an optically diffusive medium following ultrashort laser pulse excitation is evaluated using complex analytical methods. When expressed as a Fourier integral, the integrand of the time-resolved diffuse ... ...

    Abstract The spatiotemporal evolution of fluorescence in an optically diffusive medium following ultrashort laser pulse excitation is evaluated using complex analytical methods. When expressed as a Fourier integral, the integrand of the time-resolved diffuse fluorescence with embedded fluorophores is shown to exhibit branch points and simple pole singularities in the lower-half complex-frequency plane. Applying Cauchy's integral theorem to solve the Fourier integral, we calculate the time-resolved signal for fluorescence lifetimes that are both shorter and longer compared to the intrinsic absorption timescale of the medium. These expressions are derived for sources and detectors that are in the form of localized points and wide-field harmonic spatial patterns. The accuracy of the expressions derived from complex analysis is validated against the numerically computed, full time-resolved fluorescence signal. The complex analysis shows that the branch points and simple poles contribute to two physically distinct terms in the net fluorescence signal. While the branch points result in a diffusive term that exhibits spatial broadening (corresponding to a narrowing with time in the spatial Fourier domain), the simple poles lead to fluorescence decay terms with spatial/spatial-frequency distributions that are independent of time. This distinct spatiotemporal behavior between the diffuse and fluorescence signals forms the basis for direct measurement of lifetimes shorter than the intrinsic optical diffusion timescales in a turbid medium.
    Language English
    Publishing date 2020-05-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 283633-6
    ISSN 1520-8532 ; 1084-7529 ; 0740-3232
    ISSN (online) 1520-8532
    ISSN 1084-7529 ; 0740-3232
    DOI 10.1364/JOSAA.388762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Fluorescence lifetime detection in turbid media using spatial frequency domain filtering of time domain measurements.

    Kumar, Anand T N

    Optics letters

    2013  Volume 38, Issue 9, Page(s) 1440–1442

    Abstract: It is demonstrated that high spatial frequency filtering of time domain fluorescence signals can allow efficient detection of intrinsic fluorescence lifetimes from turbid media and the rejection of diffuse excitation leakage. The basis of this approach ... ...

    Abstract It is demonstrated that high spatial frequency filtering of time domain fluorescence signals can allow efficient detection of intrinsic fluorescence lifetimes from turbid media and the rejection of diffuse excitation leakage. The basis of this approach is the separation of diffuse fluorescence signals into diffuse and fluorescent components with distinct spatiotemporal behavior.
    MeSH term(s) Fluorescent Dyes/chemistry ; Light ; Phantoms, Imaging ; Spatio-Temporal Analysis ; Spectrometry, Fluorescence/methods ; Time Factors
    Chemical Substances Fluorescent Dyes
    Language English
    Publishing date 2013-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/OL.38.001440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Tomographic fluorescence lifetime multiplexing in the spatial frequency domain.

    Kumar, Anand T N / Hou, Steven S / Rice, William L

    Optica

    2018  Volume 5, Issue 5, Page(s) 624–627

    Abstract: The ability to simultaneously recover multiple fluorophores within biological tissue (multiplexing) can have important applications for tracking parallel disease ... ...

    Abstract The ability to simultaneously recover multiple fluorophores within biological tissue (multiplexing) can have important applications for tracking parallel disease processes
    Language English
    Publishing date 2018-05-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2779175-0
    ISSN 2334-2536
    ISSN 2334-2536
    DOI 10.1364/OPTICA.5.000624
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Tomographic phosphorescence lifetime multiplexing.

    Kumar, Anand T N / Hou, Steven S

    Optics letters

    2018  Volume 43, Issue 13, Page(s) 3104–3107

    Abstract: We present a tomographic reconstruction algorithm for recovering distributions of multiple phosphorescent dyes within turbid media from time-resolved measurements, using either point or spatially patterned sources and detectors. The algorithm employs a ... ...

    Abstract We present a tomographic reconstruction algorithm for recovering distributions of multiple phosphorescent dyes within turbid media from time-resolved measurements, using either point or spatially patterned sources and detectors. The algorithm employs a multi-exponential analysis of time-resolved data, followed by tomographic inversion of the decay amplitudes to recover independent yield distributions for each lifetime present in the medium. Using Monte Carlo simulations, we computationally demonstrate that this two-step inversion approach provides several-fold improvement in quantitative and localization accuracy compared to a direct inversion of the time domain phosphorescence. We also demonstrate the tomographic reconstruction of up to three phosphorescent lifetimes embedded in thick tissue. The proposed algorithm can allow quantitative multiplexed tomography of luminescent and phosphorescent dyes for a wide range of in vivo applications.
    Language English
    Publishing date 2018-06-28
    Publishing country United States
    Document type Journal Article
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/OL.43.003104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Resolution Matrix in Tomographic Multiplexing: Optimization of Inter-Parameter Cross-Talk, Relative Quantitation, and Localization.

    Hou, Steven S / Bacskai, Brian J / Kumar, Anand T N

    IEEE transactions on bio-medical engineering

    2018  Volume 66, Issue 8, Page(s) 2341–2351

    Abstract: Objective: 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.: Methods: We consider three inversion methods; an ... ...

    Abstract Objective: 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.
    Methods: 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.
    Results: 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.
    Conclusion: The ATD and CCTD inversion methods provide significant advantages over DTD for accurately estimating multiple overlapping fluorophores.
    Significance: 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.
    MeSH term(s) Algorithms ; Bayes Theorem ; Molecular Imaging/methods ; Monte Carlo Method ; Phantoms, Imaging ; Tomography, Optical/methods
    Language English
    Publishing date 2018-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 160429-6
    ISSN 1558-2531 ; 0018-9294
    ISSN (online) 1558-2531
    ISSN 0018-9294
    DOI 10.1109/TBME.2018.2889043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Direct Monte Carlo computation of time-resolved fluorescence in heterogeneous turbid media.

    Kumar, Anand T N

    Optics letters

    2012  Volume 37, Issue 22, Page(s) 4783–4785

    Abstract: We show that a multiexponential model for time-resolved fluorescence allows the use of an absorption-perturbation Monte Carlo (MC) approach based on stored photon path histories. This enables the rapid fitting of fluorescence yield, lifetimes, and ... ...

    Abstract We show that a multiexponential model for time-resolved fluorescence allows the use of an absorption-perturbation Monte Carlo (MC) approach based on stored photon path histories. This enables the rapid fitting of fluorescence yield, lifetimes, and background tissue absorptions in complex heterogeneous media within a few seconds, without the need for temporal convolutions or MC recalculation of photon path lengths. We validate this method using simulations with both a slab and a heterogeneous model of the mouse head.
    MeSH term(s) Absorption ; Animals ; Brain/metabolism ; Mice ; Monte Carlo Method ; Photons ; Spectrometry, Fluorescence/methods ; Time Factors
    Language English
    Publishing date 2012-11-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/ol.37.004783
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Fluorescence Lifetime-Based Tumor Contrast Enhancement Using an EGFR Antibody-Labeled Near-Infrared Fluorophore.

    Pal, Rahul / Kang, Homan / Choi, Hak Soo / Kumar, Anand T N

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2019  Volume 25, Issue 22, Page(s) 6653–6661

    Abstract: Purpose: Imaging techniques for highly specific detection of cancer cells : Experimental design: Mice bearing MDA-MB-231 tumors were injected with anti-EGFR antibody conjugated to the fluorescent dye IRDye 800CW (anti-EGFR-800). Time domain ... ...

    Abstract Purpose: Imaging techniques for highly specific detection of cancer cells
    Experimental design: Mice bearing MDA-MB-231 tumors were injected with anti-EGFR antibody conjugated to the fluorescent dye IRDye 800CW (anti-EGFR-800). Time domain fluorescence imaging was performed
    Results: Mice injected with anti-EGFR-800 showed a significantly longer FLT (0.7 ± 0.03 ns) compared with the FLT of nonspecific probe uptake in liver (0.63 ± 0.05 ns), providing a dramatic improvement in sensitivity and specificity compared with CW intensity. IgG antibody-conjugated IRDye 800CW did not show an increased FLT compared with normal tissue, suggesting that the FLT increase of anti-EGFR-800 in tumors was associated with receptor expression. Using serial surgery, we show that FLT allows the detection of smaller residual tumors in the surgical bed than possible using CW intensity.
    Conclusions: Our data suggest that FLT can significantly enhance tumor contrast using fluorescently labeled antibodies, thereby accelerating the efficient clinical application of these probes for margin assessment in image-guided surgery and for highly specific detection of tumor receptors
    MeSH term(s) Animals ; Antibodies, Monoclonal ; Biopsy ; Cell Line, Tumor ; Disease Models, Animal ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; Fluorescent Dyes/metabolism ; Heterografts ; Humans ; Image Enhancement ; Immunohistochemistry ; Mice ; Microscopy, Fluorescence ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/surgery ; Optical Imaging/methods
    Chemical Substances Antibodies, Monoclonal ; Fluorescent Dyes ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2019-09-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-19-1686
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: In vivo

    Pal, Rahul / K, Murali / Matsui, Aya / Kang, Homan / Morita, Satoru / Taniguchi, Hajime / Kobayashi, Tatsuya / Morita, Atsuyo / Choi, Hak Soo / Duda, Dan G / Kumar, Anand T N

    Research square

    2023  

    Abstract: Cancer patient selection for immunotherapy is often based on programmed death-ligand-1 (PD-L1) expression as a biomarker. PD-L1 expression is currently quantified using immunohistochemistry, which can only provide snapshots of PD-L1 expression status in ... ...

    Abstract Cancer patient selection for immunotherapy is often based on programmed death-ligand-1 (PD-L1) expression as a biomarker. PD-L1 expression is currently quantified using immunohistochemistry, which can only provide snapshots of PD-L1 expression status in microscopic regions of
    Language English
    Publishing date 2023-10-23
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3222037/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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