Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging

Abstract

Optical coherence tomography (OCT) provides high-resolution, cross-sectional imaging of tissue microstructure in situ and in real-time, while fluorescence molecular imaging (FMI) enables the visualization of basic molecular processes. There are great interests in combining these two modalities so that the tissue's structural and molecular information can be obtained simultaneously. This could greatly benefit biomedical applications such as detecting early diseases and monitoring therapeutic interventions. In this research, an optical system that combines OCT and FMI was developed. The system demonstrated that it could co-register en face OCT and FMI images with a 2.4 × 2.4 mm field of view. The transverse resolutions of OCT and FMI of the system are both ~10 μm. Capillary tubes filled with fluorescent dye Cy 5.5 in different concentrations under a scattering medium are used as the phantom. En face OCT images of the phantoms were obtained and successfully co-registered with FMI images that were acquired simultaneously. A linear relationship between FMI intensity and dye concentration was observed. The relationship between FMI intensity and target fluorescence tube depth measured by OCT images was also observed and compared with theoretical modeling. This relationship could help in correcting reconstructed dye concentration. Imaging of colon polyps of APC min mouse model is presented as an example of biological applications of this co-registered OCT/FMI system.

High-dynamic-range fluorescence laminar optical tomography (HDR-FLOT)

“…The OCT system shown in Fig. 1(B) was described previously [7,[26][27][28]. A wavelength-swept laser centered at 1310 nm with a 100-nm bandwidth was used in this frequency-domain OCT system as a light source [7,26,27].…”

“…The wavelength-swept frequency was 16 kHz and the output power from the laser was approximately 16 mW. About 97% of the laser power was split 50:50 to the sample and the reference arms of a fiber-based Michelson interferometer [7,26,27]. A balanced detector (BD) was used to receive the interference fringes from different depths encoded with different frequencies.…”

“…A balanced detector (BD) was used to receive the interference fringes from different depths encoded with different frequencies. The remaining 3% of the laser output power was sent to a Mach-Zehnder interferometer (MZI) to generate a frequency-clock signal with a uniformly spaced optical frequency to trigger the sampling of the OCT signal [7,26,27]. Then, a fast Fourier transform of the interference fringes was performed to obtain the depthresolved axial profile [7,26,27].…”

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography

“…Depth-resolved tomography can be achieved by performing fast Fourier transform of the interference fringes. During imaging, the colon tissue was irrigated by phosphate buffer saline (PBS) to prevent dehydration [59].…”

A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography

“…Thus, optical components capable of operating at these two very different wavelength ranges are required to combine the two modalities. Several groups have published methods for combining OCT and AF imaging using free space optical components and dichroic mirrors [11][12][13][14][15][16]. For endoscopic imaging such as in lung, the need for fiber optic catheters creates additional challenges.…”