skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Superresolution Diffuse Optical Imaging by Localization of Fluorescence

Abstract

The multiple scattering of light presents major challenges in realizing useful in vivo imaging at tissue depths of more than about one millimeter, where many answers to health questions lie. Visible through near-infrared photons can be readily and safely detected through centimeters of tissue; however, limited information is available for image formation. One strategy for obtaining images is to model the photon transport and a simple incoherent model is the diffusion equation approximation to the Boltzmann transport equation. Such an approach provides a prediction of the mean intensity of heavily scattered light and hence provides a forward model for optimization-based computational imaging. While diffuse optical imaging methods have received substantial attention, they remain restricted in terms of resolution because of the loss of high-spatial-frequency information that is associated with the multiple scattering of photons. Consequently, only relatively large inhomogeneities, such as tumors or organs in small animals, can be effectively resolved. We introduce a superresolution imaging approach based on point localization in a diffusion framework that enables over two orders of magnitude improvement in the spatial resolution of diffuse optical imaging. The method is demonstrated experimentally by localizing a fluorescent inhomogeneity in a highly scattering slab and characterizing the localizationmore » uncertainty. The approach allows imaging through centimeters of tissue with a resolution of tens of microns, thereby enabling cells or cell clusters to be resolved. More generally, this high-resolution imaging approach could be applied with any physical transport or wave model and hence to a broad class of physical problems. Finally, paired with a suitable optical contrast mechanism, as can be realized with targeted fluorescent molecules or genetically modified animals, superresolution diffuse imaging should open alternative dimensions for in vivo applications.« less

Authors:
 [1];  [2];  [2]
  1. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Purdue Univ., West Lafayette, IN (United States)
  2. Purdue Univ., West Lafayette, IN (United States)
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Purdue Univ., West Lafayette, IN (United States)
Sponsoring Org.:
USDOE; National Science Foundation (NSF); National Inst. of Health (NIH) (United States)
OSTI Identifier:
1477869
Report Number(s):
SAND2018-5205J
Journal ID: ISSN 2331-7019; 663157
Grant/Contract Number:  
NA0003525; CISE-1218909; CISE-1618908; 1R21CA182235-01A1
Resource Type:
Accepted Manuscript
Journal Name:
Physical Review Applied
Additional Journal Information:
Journal Volume: 10; Journal Issue: 3; Journal ID: ISSN 2331-7019
Publisher:
American Physical Society (APS)
Country of Publication:
United States
Language:
English
Subject:
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS; classical optics; imaging & optical processing; light-matter interaction; fluorescence; medical imaging; static light scattering; super-resolution techniques

Citation Formats

Bentz, Brian Z., Lin, Dergan, and Webb, Kevin J. Superresolution Diffuse Optical Imaging by Localization of Fluorescence. United States: N. p., 2018. Web. doi:10.1103/PhysRevApplied.10.034021.
Bentz, Brian Z., Lin, Dergan, & Webb, Kevin J. Superresolution Diffuse Optical Imaging by Localization of Fluorescence. United States. doi:10.1103/PhysRevApplied.10.034021.
Bentz, Brian Z., Lin, Dergan, and Webb, Kevin J. Tue . "Superresolution Diffuse Optical Imaging by Localization of Fluorescence". United States. doi:10.1103/PhysRevApplied.10.034021. https://www.osti.gov/servlets/purl/1477869.
@article{osti_1477869,
title = {Superresolution Diffuse Optical Imaging by Localization of Fluorescence},
author = {Bentz, Brian Z. and Lin, Dergan and Webb, Kevin J.},
abstractNote = {The multiple scattering of light presents major challenges in realizing useful in vivo imaging at tissue depths of more than about one millimeter, where many answers to health questions lie. Visible through near-infrared photons can be readily and safely detected through centimeters of tissue; however, limited information is available for image formation. One strategy for obtaining images is to model the photon transport and a simple incoherent model is the diffusion equation approximation to the Boltzmann transport equation. Such an approach provides a prediction of the mean intensity of heavily scattered light and hence provides a forward model for optimization-based computational imaging. While diffuse optical imaging methods have received substantial attention, they remain restricted in terms of resolution because of the loss of high-spatial-frequency information that is associated with the multiple scattering of photons. Consequently, only relatively large inhomogeneities, such as tumors or organs in small animals, can be effectively resolved. We introduce a superresolution imaging approach based on point localization in a diffusion framework that enables over two orders of magnitude improvement in the spatial resolution of diffuse optical imaging. The method is demonstrated experimentally by localizing a fluorescent inhomogeneity in a highly scattering slab and characterizing the localization uncertainty. The approach allows imaging through centimeters of tissue with a resolution of tens of microns, thereby enabling cells or cell clusters to be resolved. More generally, this high-resolution imaging approach could be applied with any physical transport or wave model and hence to a broad class of physical problems. Finally, paired with a suitable optical contrast mechanism, as can be realized with targeted fluorescent molecules or genetically modified animals, superresolution diffuse imaging should open alternative dimensions for in vivo applications.},
doi = {10.1103/PhysRevApplied.10.034021},
journal = {Physical Review Applied},
number = 3,
volume = 10,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 1 work
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Imaging Optical Fields Through Heavily Scattering Media
journal, December 2014


Looking and listening to light: the evolution of whole-body photonic imaging
journal, March 2005

  • Ntziachristos, Vasilis; Ripoll, Jorge; Wang, Lihong V.
  • Nature Biotechnology, Vol. 23, Issue 3, p. 313-320
  • DOI: 10.1038/nbt1074

Stimulated Emission Depletion Microscopy
journal, March 2017


Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal studies
journal, January 2003


Diffuse optical localization of blood vessels and 3D printing for guiding oral surgery
journal, January 2017

  • Bentz, Brian Z.; Wu, Timothy C.; Gaind, Vaibhav
  • Applied Optics, Vol. 56, Issue 23
  • DOI: 10.1364/AO.56.006649

Imaging Intracellular Fluorescent Proteins at Nanometer Resolution
journal, September 2006


Refraction of diffuse photon density waves
journal, November 1992


In vivo mouse fluorescence imaging for folate-targeted delivery and release kinetics
journal, January 2014

  • Tsai, Esther H. R.; Bentz, Brian Z.; Chelvam, Venkatesh
  • Biomedical Optics Express, Vol. 5, Issue 8
  • DOI: 10.1364/BOE.5.002662

MRI-Guided Diffuse Optical Spectroscopy of Malignant and Benign Breast Lesions
journal, January 2002

  • Ntziachristos, Vasilis; Yodh, A. G.; Schnall, Mitchell D.
  • Neoplasia, Vol. 4, Issue 4
  • DOI: 10.1038/sj.neo.7900244

Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue
journal, August 2015


Improving the diffuse optical imaging spatial resolution of the cerebral hemodynamic response to brain activation in humans
journal, January 2004


Analysis and optimization of a diffuse photon optical tomography of turbid media
journal, August 2000


Localization of an absorbing inhomogeneity in a scattering medium in a statistical framework
journal, January 2007

  • Cao, Guangzhi; Gaind, Vaibhav; Bouman, Charles A.
  • Optics Letters, Vol. 32, Issue 20
  • DOI: 10.1364/OL.32.003026

Nonlinear multigrid algorithms for Bayesian optical diffusion tomography
journal, June 2001

  • Jong Chul Ye, ; Bouman, C. A.; Webb, K. J.
  • IEEE Transactions on Image Processing, Vol. 10, Issue 6
  • DOI: 10.1109/83.923287

Boundary conditions for the diffusion equation in radiative transfer
journal, January 1994

  • Haskell, Richard C.; Svaasand, Lars O.; Tsay, Tsong-Tseh
  • Journal of the Optical Society of America A, Vol. 11, Issue 10
  • DOI: 10.1364/JOSAA.11.002727

Optical diffusion imaging using a direct inversion method
journal, October 1995


Diffusive media characterization with laser speckle
journal, January 1997

  • Thompson, Charles A.; Webb, Kevin J.; Weiner, Andrew M.
  • Applied Optics, Vol. 36, Issue 16
  • DOI: 10.1364/AO.36.003726

Resolution limits for imaging through turbid media with diffuse light
journal, January 1993


Imaging Hidden Objects with Spatial Speckle Intensity Correlations over Object Position
journal, February 2016


Localization of luminescent inhomogeneities in turbid media with spatially resolved measurements of cw diffuse luminescence emittance
journal, January 1998

  • Hull, Edward L.; Nichols, Michael G.; Foster, Thomas H.
  • Applied Optics, Vol. 37, Issue 13
  • DOI: 10.1364/AO.37.002755

Functional imaging and localization of electromagnetic brain activity
journal, January 1992


Precise Nanometer Localization Analysis for Individual Fluorescent Probes
journal, May 2002


Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM)
journal, August 2006

  • Rust, Michael J.; Bates, Mark; Zhuang, Xiaowei
  • Nature Methods, Vol. 3, Issue 10
  • DOI: 10.1038/nmeth929

Optical diffusion tomography by iterative-coordinate-descent optimization in a Bayesian framework
journal, January 1999

  • Ye, Jong Chul; Webb, Kevin J.; Bouman, Charles A.
  • Journal of the Optical Society of America A, Vol. 16, Issue 10
  • DOI: 10.1364/JOSAA.16.002400

Symmetries, inversion formulas, and image reconstruction for optical tomography
journal, November 2004


α-Synuclein strains cause distinct synucleinopathies after local and systemic administration
journal, June 2015

  • Peelaerts, W.; Bousset, L.; Van der Perren, A.
  • Nature, Vol. 522, Issue 7556
  • DOI: 10.1038/nature14547

Resolution limits for optical transillumination of abnormalities deeply embedded in tissues
journal, February 1994

  • Gandjbakhche, A. H.; Nossal, R.; Bonner, R. F.
  • Medical Physics, Vol. 21, Issue 2
  • DOI: 10.1118/1.597298

Application of the finite-element method for the forward and inverse models in optical tomography
journal, September 1993

  • Schweiger, M.; Arridge, S. R.; Delpy, D. T.
  • Journal of Mathematical Imaging and Vision, Vol. 3, Issue 3
  • DOI: 10.1007/BF01248356

Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes
journal, December 2016


Spatial-frequency-compression scheme for diffuse optical tomography with dense sampling dataset
journal, January 2013


Anisotropic effects in highly scattering media
journal, September 2003


Nonlinear Microwave Imaging for Breast-Cancer Screening Using Gauss–Newton's Method and the CGLS Inversion Algorithm
journal, August 2007

  • Rubek, Tonny; Meaney, Paul M.; Meincke, Peter
  • IEEE Transactions on Antennas and Propagation, Vol. 55, Issue 8
  • DOI: 10.1109/TAP.2007.901993

Multigrid tomographic inversion with variable resolution data and image spaces
journal, September 2006

  • Seungseok Oh, ; Bouman, C. A.; Webb, K. J.
  • IEEE Transactions on Image Processing, Vol. 15, Issue 9
  • DOI: 10.1109/TIP.2006.877313

Free-Space Propagation of Diffuse Light: Theory and Experiments
journal, September 2003


Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy
journal, May 2014

  • Prevedel, Robert; Yoon, Young-Gyu; Hoffmann, Maximilian
  • Nature Methods, Vol. 11, Issue 7
  • DOI: 10.1038/nmeth.2964

Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung
journal, December 1873


Kirchhoff approximation for diffusive waves
journal, October 2001


Spatial resolution of diffuse photon density waves
journal, January 1999

  • Ripoll, J.; Nieto-Vesperinas, M.; Carminati, Rémi
  • Journal of the Optical Society of America A, Vol. 16, Issue 6
  • DOI: 10.1364/JOSAA.16.001466

Ultra-High Resolution Imaging by Fluorescence Photoactivation Localization Microscopy
journal, December 2006


Maximum likelihood tomographic reconstruction of extremely sparse solutions in diffuse fluorescence flow cytometry
journal, January 2013

  • Pera, Vivian; Zettergren, Eric; Brooks, Dana H.
  • Optics Letters, Vol. 38, Issue 13
  • DOI: 10.1364/OL.38.002357

Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media
journal, April 2002

  • Ntziachristos, Vasilis; Weissleder, Ralph
  • Medical Physics, Vol. 29, Issue 5
  • DOI: 10.1118/1.1470209

The Toast++ software suite for forward and inverse modeling in optical tomography
journal, April 2014


Improved localization of hidden fluorescent objects in highly scattering slab media based on a two-way transmittance determination
journal, January 2006

  • L'Huillier, Jean-Pierre; Vaudelle, Fabrice
  • Optics Express, Vol. 14, Issue 26
  • DOI: 10.1364/OE.14.012915

Blinking statistics in single semiconductor nanocrystal quantum dots
journal, May 2001


Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media
journal, March 2010


Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications
journal, January 1996

  • Li, X. D.; O'Leary, M. A.; Boas, D. A.
  • Applied Optics, Vol. 35, Issue 19
  • DOI: 10.1364/AO.35.003746

Real-time diffuse optical tomography based on structured illumination
journal, January 2010

  • Bélanger, Samuel; Abran, Maxime; Intes, Xavier
  • Journal of Biomedical Optics, Vol. 15, Issue 1
  • DOI: 10.1117/1.3290818

Light focusing and two-dimensional imaging through scattering media using the photoacoustic transmission matrix with an ultrasound array
journal, January 2014

  • Chaigne, Thomas; Gateau, Jérôme; Katz, Ori
  • Optics Letters, Vol. 39, Issue 9
  • DOI: 10.1364/OL.39.002664

Fluorescence optical diffusion tomography
journal, January 2003

  • Milstein, Adam B.; Oh, Seungseok; Webb, Kevin J.
  • Applied Optics, Vol. 42, Issue 16
  • DOI: 10.1364/AO.42.003081

A submillimeter resolution fluorescence molecular imaging system for small animal imaging
journal, April 2003

  • Graves, Edward E.; Ripoll, Jorge; Weissleder, Ralph
  • Medical Physics, Vol. 30, Issue 5
  • DOI: 10.1118/1.1568977

Mapping distributed brain function and networks with diffuse optical tomography
journal, May 2014

  • Eggebrecht, Adam T.; Ferradal, Silvina L.; Robichaux-Viehoever, Amy
  • Nature Photonics, Vol. 8, Issue 6
  • DOI: 10.1038/nphoton.2014.107

Comparison of imaging geometries for diffuse optical tomography of tissue
journal, January 1999

  • Pogue, Brian W.; McBride, Troy O.; Osterberg, Ulf L.
  • Optics Express, Vol. 4, Issue 8
  • DOI: 10.1364/OE.4.000270

Diffraction tomography for biochemical imaging with diffuse-photon density waves
journal, January 1997


Complex brain networks: graph theoretical analysis of structural and functional systems
journal, February 2009

  • Bullmore, Ed; Sporns, Olaf
  • Nature Reviews Neuroscience, Vol. 10, Issue 3
  • DOI: 10.1038/nrn2575

Efficient multi-site two-photon functional imaging of neuronal circuits
journal, January 2016

  • Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack
  • Biomedical Optics Express, Vol. 7, Issue 12
  • DOI: 10.1364/BOE.7.005325

Focusing through random media: Eigenchannel participation number and intensity correlation
journal, January 2012


Localization of fluorescence spots with space-space MUSIC for mammographylike measurement systems
journal, January 2004

  • Pfister, Marcus; Scholz, Bernhard
  • Journal of Biomedical Optics, Vol. 9, Issue 3
  • DOI: 10.1117/1.1698981

Electrical Impedance Tomography
journal, January 1999


All Photons Imaging Through Volumetric Scattering
journal, September 2016

  • Satat, Guy; Heshmat, Barmak; Raviv, Dan
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep33946

Universal back-projection algorithm for photoacoustic computed tomography
journal, January 2005


Statistical approach for detection and localization of a fluorescing mouse tumor in Intralipid
journal, January 2005

  • Milstein, Adam B.; Kennedy, Michael D.; Low, Philip S.
  • Applied Optics, Vol. 44, Issue 12
  • DOI: 10.1364/AO.44.002300

Recent advances in diffuse optical imaging
journal, February 2005