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Superresolution Diffuse Optical Imaging by Localization of Fluorescence

Journal Article · · Physical Review Applied
 [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)

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.

Research Organization:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Purdue Univ., West Lafayette, IN (United States)
Sponsoring Organization:
USDOE; National Science Foundation (NSF) (United States); National Inst. of Health (NIH) (United States)
Grant/Contract Number:
NA0003525
OSTI ID:
1477869
Report Number(s):
SAND2018--5205J; 663157
Journal Information:
Physical Review Applied, Journal Name: Physical Review Applied Journal Issue: 3 Vol. 10; ISSN 2331-7019
Publisher:
American Physical Society (APS)Copyright Statement
Country of Publication:
United States
Language:
English

References (66)

Functional imaging and localization of electromagnetic brain activity journal January 1992
Application of the finite-element method for the forward and inverse models in optical tomography journal September 1993
Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung journal December 1873
Precise Nanometer Localization Analysis for Individual Fluorescent Probes journal May 2002
The integration of 3-D cell printing and mesoscopic fluorescence molecular tomography of vascular constructs within thick hydrogel scaffolds journal July 2012
Stimulated Emission Depletion Microscopy journal March 2017
α-Synuclein strains cause distinct synucleinopathies after local and systemic administration journal June 2015
Looking and listening to light: the evolution of whole-body photonic imaging journal March 2005
Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy journal May 2014
Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM) journal August 2006
Mapping distributed brain function and networks with diffuse optical tomography journal May 2014
Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue journal August 2015
Complex brain networks: graph theoretical analysis of structural and functional systems journal February 2009
MRI-Guided Diffuse Optical Spectroscopy of Malignant and Benign Breast Lesions journal January 2002
All Photons Imaging Through Volumetric Scattering journal September 2016
Recent advances in diffuse optical imaging journal February 2005
Blinking statistics in single semiconductor nanocrystal quantum dots journal May 2001
Focusing through random media: Eigenchannel participation number and intensity correlation journal January 2012
Optical diffusion imaging using a direct inversion method journal October 1995
Analysis and optimization of a diffuse photon optical tomography of turbid media journal August 2000
Kirchhoff approximation for diffusive waves journal October 2001
Anisotropic effects in highly scattering media journal September 2003
Symmetries, inversion formulas, and image reconstruction for optical tomography journal November 2004
Universal back-projection algorithm for photoacoustic computed tomography journal January 2005
Mean square displacement analysis of single-particle trajectories with localization error: Brownian motion in an isotropic medium journal October 2010
Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media journal March 2010
Imaging Optical Fields Through Heavily Scattering Media journal December 2014
Imaging Hidden Objects with Spatial Speckle Intensity Correlations over Object Position journal February 2016
Refraction of diffuse photon density waves journal November 1992
Free-Space Propagation of Diffuse Light: Theory and Experiments journal September 2003
Nonlinear multigrid algorithms for Bayesian optical diffusion tomography journal June 2001
Nonlinear Microwave Imaging for Breast-Cancer Screening Using Gauss–Newton's Method and the CGLS Inversion Algorithm journal August 2007
Multigrid tomographic inversion with variable resolution data and image spaces journal September 2006
Localization of fluorescence spots with space-space MUSIC for mammographylike measurement systems journal January 2004
Real-time diffuse optical tomography based on structured illumination journal January 2010
The Toast++ software suite for forward and inverse modeling in optical tomography journal April 2014
Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media journal April 2002
A submillimeter resolution fluorescence molecular imaging system for small animal imaging journal April 2003
Resolution limits for optical transillumination of abnormalities deeply embedded in tissues journal February 1994
Imaging Intracellular Fluorescent Proteins at Nanometer Resolution journal September 2006
Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes journal December 2016
Electrical Impedance Tomography journal January 1999
Seismic waveform inversion in the frequency domain, Part 1: Theory and verification in a physical scale model journal May 1999
Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications journal January 1996
Diffusive media characterization with laser speckle journal January 1997
Localization of luminescent inhomogeneities in turbid media with spatially resolved measurements of cw diffuse luminescence emittance journal January 1998
Fluorescence optical diffusion tomography journal January 2003
Statistical approach for detection and localization of a fluorescing mouse tumor in Intralipid journal January 2005
Spatial-frequency-compression scheme for diffuse optical tomography with dense sampling dataset journal January 2013
Diffuse optical localization of blood vessels and 3D printing for guiding oral surgery journal January 2017
In vivo mouse fluorescence imaging for folate-targeted delivery and release kinetics journal January 2014
Efficient multi-site two-photon functional imaging of neuronal circuits journal January 2016
Boundary conditions for the diffusion equation in radiative transfer journal January 1994
Spatial resolution of diffuse photon density waves journal January 1999
Optical diffusion tomography by iterative-coordinate-descent optimization in a Bayesian framework journal January 1999
Improved localization of hidden fluorescent objects in highly scattering slab media based on a two-way transmittance determination journal January 2006
Comparison of imaging geometries for diffuse optical tomography of tissue journal January 1999
Resolution limits for imaging through turbid media with diffuse light journal January 1993
Diffraction tomography for biochemical imaging with diffuse-photon density waves journal January 1997
High-resolution near-infrared tomographic imaging simulations of the rat cranium by use of a priori magnetic resonance imaging structural information journal January 1998
Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal studies journal January 2003
Improving the diffuse optical imaging spatial resolution of the cerebral hemodynamic response to brain activation in humans journal January 2004
Localization of an absorbing inhomogeneity in a scattering medium in a statistical framework journal January 2007
Maximum likelihood tomographic reconstruction of extremely sparse solutions in diffuse fluorescence flow cytometry journal January 2013
Light focusing and two-dimensional imaging through scattering media using the photoacoustic transmission matrix with an ultrasound array journal January 2014
Ultra-High Resolution Imaging by Fluorescence Photoactivation Localization Microscopy journal December 2006

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