Angle-resolved Low Coherence Interferometry (a/LCI)

Angle-resolved low-coherence interferometry (a/LCI) is a breakthrough biomedical imaging technology which uses the properties of scattered light to measure the average size of cell structures, including cell nuclei.  The technology shows promise as a clinical tool for in situ tissue measurements.

a/LCI combines low-coherence interferometry with angle-resolved scattering to solve the inverse problem of determining scatterer geometry based on far field diffraction patterns.  Similar to optical coherence domain reflectometry (OCDR) and optical coherence tomography (OCT), a/LCI uses a broadband light source in an interferometry scheme in order to achieve optical sectioning with a depth resolution set by the coherence length of the source.  Angle-resolved scattering measurements capture light as a function of the scattering angle, and invert the scattering distribution which predicts the distribution based on a computational light scattering model such as Mie theory, which predicts angles based on the size of the scattering sphere.  Combining these techniques allows construction of a system that can measure average scatter size at various depths within a tissue sample.

Example results of
a Fourier-domain a/LCI

The a/LCI system was converted to a Fourier domain implementation to provide depth resolved data across an entire tissue section in a single data acquisition.  A broadband light source is used to produce a spectrum of wavelengths at once, and the backscattered light is collected by a coherent optical fiber in the return path to capture different scattering angles simultaneously.  Intensity is then measured via a spectrometer: a single frame from the spectrometer contains scattering intensity as a function of wavelength and angle.  Data are Fourier transformed on a line-by-line basis to generate scattering intensity as a function of depth and angle.  Using this method, the acquisition speed is limited only by the integration time of the spectrometer and may be as short as 20 milliseconds.  The same data that initially required tens of minutes to acquire can now be acquired ~105 times faster.  Oncoscopes's clinical prototype is based on the Fourier domain implementation of a/LCI.

schematic of a/LCI system
Schematic of a/LCI System

The Fourier-domain version of the a/LCI system uses a superluminescent diode (SLD) with a fiber-coupled output as the light source.  A fiber splitter separates the signal path at 90% intensity and the reference path at 10%.

The light from the SLD passes through an optical isolator and subsequently a polarization controller.  It has been shown that control of light polarization is important for maximizing optical signal and comparing angular scattering with the Mie scattering model.  A polarization-maintaining fiber is used to carry the illumination light to the sample.  A second polarization controller is similarly used to control the polarization of the light passing through the reference path.

The output of the fiber on the right is collimated using lens L1 and illuminates the tissue.  But because the delivery fiber is offset from the optical axis of the lens, the beam is delivered to the sample at an oblique angle.  Backscattered light is then collimated by the same lens and collected by the fiber bundle.  The fibers are one focal length from the lens, and the sample is one focal length on the other side.  This configuration captures light from the maximum range of angles and minimizes light noise due to specular reflections. 

At the proximal end of the fiber bundle, light from each fiber is imaged onto the spectrometer.  Light from the sample and reference arms are mixed by a beamsplitting cube (BS), and are incident on the entrance slit of an imaging spectrometer.  Data from the imaging spectrometer are transferred to a computer via universal serial bus interface for signal processing and display of results.  The computer also provides control of the imaging spectrometer.

Further technical information can be found in the Publications section of this website and at: http://en.wikipedia.org/wiki/Angle-resolved_low-coherence_interferometry#cite_note-0.