Method and system for near-infrared fluorescence contrast-enhanced imaging with area illumination and area detection

Inventors

Sevick-Muraca, Eva M.Thompson, Alan B.Ranadhir, Roy

Assignees

Texas A&M University SystemTexas A&M University

Publication Number

US-7599732-B2

Publication Date

2009-10-06

Expiration Date

2024-06-18

Interested in licensing this patent?

MTEC can help explore whether this patent might be available for licensing for your application.


Abstract

According to one embodiment of the invention, a method for biomedical imaging includes directing time-varying excitation light at a surface area of a light scattering material, the material comprising a fluorescent target. Time-varying emission light from the fluorescent target is detected, substantially at a two-dimensional sensor surface, in response to the time-varying excitation light stimulating the fluorescent target. The time-varying emission light is filtered to reject excitation light re-emitted from the material. A three-dimensional image of the fluorescent target is generated based on the detection substantially at the sensor surface.

Core Innovation

The invention provides a method and system for near-infrared fluorescence contrast-enhanced biomedical imaging using area illumination and area detection. Time-varying excitation light is directed at a surface area of a light scattering material or tissue containing a fluorescent target. Emission light stimulated by this excitation is detected substantially at a two-dimensional sensor surface. The detected emission light is filtered to reject excitation light re-emitted from the material, and a three-dimensional image of the fluorescent target is generated based on these detections.

The problem addressed arises from prior art methods that use point illumination and point detection with fiber optics, which may fail to sufficiently excite fluorescent targets and produce sparse data sets, making the inverse problem of image reconstruction challenging. The invention overcomes these disadvantages by employing area illumination and area detection on the same tissue-like surface, leading to more efficient excitation of fluorophores within a large tissue volume and significantly more data, thereby improving imaging accuracy.

The method further includes determining the spatial distribution of amplitude and phase-delay of both the emission light and the incident excitation light. The incident excitation light distribution is experimentally determined using polarization techniques to separate specularly reflected excitation light from multiply scattered light, facilitating accurate modeling of light propagation. Mathematical reconstruction of a 3D image uses a modified barrier penalty function optimizing fluorescence absorption coefficients based on coupled frequency-domain diffusion equations solved with finite element methods.

Claims Coverage

The claims include two independent method claims and one independent system claim, each comprising inventive features related to near-infrared fluorescence imaging with area illumination and area detection, modulation techniques, filtering, and image reconstruction.

Time-varying excitation and area detection

Direct time-varying intensity-modulated excitation light at a surface area of tissue or scattering material containing a fluorescent target. Detect time-varying emission light substantially at a two-dimensional sensor surface in response to excitation.

Filtering of emission light to reject excitation light

Filter the time-varying emission light to reject excitation light re-emitted from the material using optical filters, enabling extraction of fluorescent emission signals.

Spatial distribution determination of amplitude and phase-delay for emission and excitation light

Determine the spatial distributions of amplitude and phase-delay of the detected emission light and also of the time-varying excitation light incident on the surface area based on detected specularly reflected excitation light.

Generation of three-dimensional fluorescence image

Generate a three-dimensional image of the fluorescent target based on the spatial distributions of the incident excitation light and the emission light, employing mathematical reconstruction of fluorescence absorption coefficients.

Modulation at radio frequency and polarization-based excitation light separation

Modulate the intensity of excitation light at a radio frequency to enable homodyne detection. Use linear polarizers in different configurations to detect and subtract multiply scattered excitation light, isolating specularly reflected excitation light for accurate determination of incident excitation light.

System components for area illumination and area detection

A system comprising a laser diode operable to direct time-varying excitation light at a surface area of a light scattering material; an image intensifier detecting emission light at a two-dimensional sensor surface; optical filters to reject excitation light; and an imaging apparatus generating a 3D image based on sensor detection.

The claims cover methods and systems that utilize time-varying, intensity-modulated excitation light over a surface area, area detection of emission light on a two-dimensional sensor, filtering techniques to reject excitation light, determination of spatial amplitude and phase-delay of both excitation and emission light, and generation of three-dimensional images of fluorescent targets. The invention includes modulation at radio frequency, polarization methods to separate excitation light components, and system components configured to perform these functions.

Stated Advantages

Area illumination excites fluorophores within a large tissue volume more efficiently than point illumination.

Area detection provides significantly more data compared to point detection.

Non-contact imaging is possible, simplifying measurement procedures.

Ability to reconstruct three-dimensional images from data collected at a two-dimensional sensor surface.

Eliminates the need for optical fibers for illumination and collection unlike traditional point illumination/collection schemes.

Documented Applications

Medical imaging of diseased tissues using fluorescent contrast agents.

Intraoperative three-dimensional identification of diseased or tumor lesion margins for effective and complete surgical resection.

JOIN OUR MAILING LIST

Stay Connected with MTEC

Keep up with active and upcoming solicitations, MTEC news and other valuable information.