Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy

Authors

  • Gibbs-Strauss Summer L.,

    1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755-8000
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    • a)

      Present address: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215; electronic mail: sgibbs@bidmc.harvard.edu

  • O'Hara Julia A.,

    1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755-8000 and Department of Diagnostic Radiology, Dartmouth Medical School, Lebanon New Hampshire 03756
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  • Srinivasan Subhadra,

    1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755-8000
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  • Hoopes P. Jack,

    1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755-8000 and Department of Surgery, Dartmouth Medical School, Lebanon New Hampshire 03756
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  • Hasan Tayyaba,

    1. Department of Dermatology, Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114
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  • Pogue Brian W.

    1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755-8000; Department of Surgery, Dartmouth Medical School, Lebanon New Hampshire 03756; and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114
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Abstract

The diffuse spread of glioma tumors leads to the inability to image and properly treat this disease. The optical spectral signature of targeted fluorescent probes provides molecular signals from the diffuse morphologies of glioma tumors, which can be a more effective diagnostic probe than standard morphology-based magnetic resonance imaging (MRI) sequences. Three orthotopic xenograft glioma models were used to examine the potential for transmitted optical fluorescence signal detection in vivo, using endogenously produced protoporphyrin IX (PpIX) and exogenously administered fluorescently labeled epidermal growth factor (EGF). Accurate quantification of the fluorescent signals required spectral filtering and signal normalization, and when optimized, it was possible to improve detection of sparse diffuse glioma tumor morphologies. The signal of endogenously produced PpIX provided similar sensitivity and specificity to MRI, while detection with fluorescently labeled EGF provided maximal specificity for tumors with high EGF receptor activity. Optical transmitted fluorescent signal may add significant benefit for clinical cases of diffuse infiltrative growth pattern glioma tumors given sufficient optimization of the signal acquisition for each patient.

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