Fluorescence imaging system and method

A system for imaging a light scattering tissue having a heterogeneous composition and containing a fluorophore, comprising:

• (a) a light source with a pre-determined time varying intensity, said source being adapted to excite the fluorophore;
• (b) a sensor configured to provide a detected light signal corresponding to a multiply scattered light emission from the tissue in response to light from said source;
• (c) a processor operatively coupled to said sensor and responsive to said detected light signal to provide a number of values representative of a level of a fluorescence characteristic of the tissue as a function of position, the level of the fluorescence characteristic varying with the heterogeneous composition of the tissue and corresponding to at least one of fluorescence lifetime, fluorescence quantum efficiency, fluorescence yield, and fluorophore uptake, said processor being configured to generate an image signal as a function of said values;
• and
• (d) an output device responsive to said image signal to provide an image corresponding to the heterogeneous composition of the tissue.

A method of tissue analysis, comprising:

• (a) exposing a biologic tissue to an excitation light with a pre-determined time varying intensity, the tissue multiply scattering the excitation light;
• (b) detecting a multiply scattered light emission from the tissue in response to said exposing;
• (c) determining a number of values from the emission with a processor, the values each corresponding to a level of a fluorescence characteristic at a different position within the tissue, the level of the characteristic varying with tissue composition;
• and
• (d) generating an image of tissue compositional variation in accordance with the values.

A method of tissue analysis, comprising:

• (a) introducing an fluorescent agent into a light scattering biologic tissue with a heterogeneous composition;
• (b) exposing the tissue to light from a light source with a pre-determined time varying intensity to excite the agent, the tissue multiply scattering the excitation light;
• (c) detecting a multiply scattered light emission from the tissue in response to said exposing;
• (d) quantitizing a fluorescence characteristic throughout the tissue from the emission by establishing a number of values with a processor, the values each corresponding to a level of the fluorescence characteristic at a different position within the tissue, the level of the fluorescence characteristic varying with heterogeneous composition of the tissue;
• and
• (e) mapping the heterogeneous composition of the tissue in accordance with the values.

A method of tissue analysis, comprising:

• (a) establishing a first set of values corresponding to adsorption and scattering properties of a light scattering biologic tissue;
• (b) introducing an fluorescent agent into the tissue after said establishing;
• (c) establishing a second set of values corresponding to adsorption and scattering properties of the tissue after said introducing;
• and
• (d) comparing the first set of values and the second set:
• of values to map uptake of the agent into the tissue.

A system for imaging a light scattering tissue having a heterogeneous composition and containing a fluorophore, comprising:

• (a) a means for exciting the fluorophore in the tissue;
• (b) a means for detecting a light signal corresponding to a fluorescent emission from the tissue in response to said exciting means;
• (c) a processor operatively coupled to said sensor and responsive to said light signal, said processor including a means for generating an output signal by iteratively estimating spatial distribution of a quantitized fluorescent characteristic of the tissue until a desired minimum error is obtained;
• and
• (d) a means for providing an image corresponding to the heterogeneous composition of the tissue in response to said output signal.

A method, comprising:

• (a) exposing a biologic tissue with a hidden heterogeneity to an excitation light with a predetermined time-varying intensity, the tissue multiply scattering the excitation light;
• (b) detecting a light emission from the tissue in response to said exposing;
• and
• (c) imaging the tissue to reveal the hidden heterogeniety by mapping spatial variation of a level of a fluorescence property of the tissue from the light emission in accordance with a mathematical relationship modeling multiple light scattering behavior of the tissue.