Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue.

Loretta Scolaro,Caroline Boudoux,Robert A Mclaughlin,Nicolas Godbout,George C Yeoh,David D Sampson,Dirk Lorenser,Wendy-Julie Madore,Rodney W Kirk,Anne S Kramer

doi:10.1364/boe.6.001767

Abstract

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue.

Highlights

Molecular imaging [1,2] provides insight into cellular dysfunction by the targeting of specific molecular markers of disease
As the light source does not have a Gaussian spectrum, the axial resolution was measured by applying a Tukey window with α = 0.1 to the sample spectrum obtained from an air/glass interface and compensated for second- and third-order dispersion to measure an axial resolution of 14 μm in air, corresponding to ~9 μm in tissue, assuming a refractive index, n, of 1.4
These results demonstrate that molecular imaging (MI) needles are capable of imaging with sensitivity comparable to benchtop fluorescence microscopes whilst enabling imaging deep within solid tissue

Summary

Introduction

Molecular imaging [1,2] provides insight into cellular dysfunction by the targeting of specific molecular markers of disease. Fluorescence-based optical molecular imaging techniques [9,10,11] typically target specific cells or signaling pathways through the use of fluorescently labeled antibodies, which comprise a protein that binds to a specific antigen, and a fluorophore that enables imaging Such labels have been developed for a wide range of disease-related targets [12,13]. Intravital microscopy [15] uses miniaturized intravascular or endoscopic scanning probes to detect molecular targets with high resolution, but is limited to cells that are located on the surfaces of blood vessels, airways or other endoscopically accessible locations Such surface imaging excludes from examination the tissue involved in many disease processes

Methods

Results

Discussion

Conclusion