TY - JOUR
T1 - Localization of Fluorescent Targets in Deep Tissue with Expanded Beam Illumination for Studies of Cancer and the Brain
AU - Bentz, Brian Z.
AU - Mahalingam, Sakkarapalayam M.
AU - Ysselstein, Daniel
AU - Montenegro Larrea, Paola C.
AU - Cannon, Jason R.
AU - Rochet, Jean Christophe
AU - Low, Philip S.
AU - Webb, Kevin
N1 - Funding Information:
Brian Z. Bentz is with Sandia National Laboratories. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525. This paper describes objective technical results and analysis. Any subjective views or opinions that might be expressed in the paper do not necessarily represent the views of the U.S. Department of Energy or the United States Government.
Funding Information:
Manuscript received November 27, 2019; accepted January 7, 2020. Date of publication February 6, 2020; date of current version June 30, 2020. This work was supported in part by the National Science Foundation under Grant CISE-1618908 and Grant CISE-1909660 and in part by the National Institutes of Health under Grant 5R21CA182235-02 and Grant 5R21NS105048-02. (Corresponding author: Kevin J. Webb.) Brian Z. Bentz is with Sandia National Laboratories, Albuquerque, NM 87123 USA (e-mail: bzbentz@sandia.gov).
Publisher Copyright:
© 1982-2012 IEEE.
PY - 2020/7
Y1 - 2020/7
N2 - Imaging fluorescence through millimeters or centimeters of tissue has important in vivo applications, such as guiding surgery and studying the brain. Often, the important information is the location of one of more optical reporters, rather than the specifics of the local geometry, motivating the need for a localization method that provides this information. We present an optimization approach based on a diffusion model for the fast localization of fluorescent inhomogeneities in deep tissue with expanded beam illumination that simplifies the experiment and the reconstruction. We show that the position of a fluorescent inhomogeneity can be estimated while assuming homogeneous tissue parameters and without having to model the excitation profile, reducing the computational burden and improving the utility of the method. We perform two experiments as a demonstration. First, a tumor in a mouse is localized using a near infrared folate-targeted fluorescent agent (OTL38). This result shows that localization can quickly provide tumor depth information, which could reduce damage to healthy tissue during fluorescence-guided surgery. Second, another near infrared fluorescent agent (ATTO647N) is injected into the brain of a rat, and localized through the intact skull and surface tissue. This result will enable studies of protein aggregation and neuron signaling.
AB - Imaging fluorescence through millimeters or centimeters of tissue has important in vivo applications, such as guiding surgery and studying the brain. Often, the important information is the location of one of more optical reporters, rather than the specifics of the local geometry, motivating the need for a localization method that provides this information. We present an optimization approach based on a diffusion model for the fast localization of fluorescent inhomogeneities in deep tissue with expanded beam illumination that simplifies the experiment and the reconstruction. We show that the position of a fluorescent inhomogeneity can be estimated while assuming homogeneous tissue parameters and without having to model the excitation profile, reducing the computational burden and improving the utility of the method. We perform two experiments as a demonstration. First, a tumor in a mouse is localized using a near infrared folate-targeted fluorescent agent (OTL38). This result shows that localization can quickly provide tumor depth information, which could reduce damage to healthy tissue during fluorescence-guided surgery. Second, another near infrared fluorescent agent (ATTO647N) is injected into the brain of a rat, and localized through the intact skull and surface tissue. This result will enable studies of protein aggregation and neuron signaling.
KW - Fluorescence imaging
KW - brain
KW - inverse problems
KW - localization
KW - tumors
KW - turbid media
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U2 - 10.1109/TMI.2020.2972200
DO - 10.1109/TMI.2020.2972200
M3 - Article
C2 - 32031935
AN - SCOPUS:85087467160
VL - 39
SP - 2472
EP - 2481
JO - IEEE Transactions on Medical Imaging
JF - IEEE Transactions on Medical Imaging
SN - 0278-0062
IS - 7
M1 - 8985382
ER -