Monitoring time-varying fluorescence emitted from an exogenous fluorescence agent

A method of monitoring time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties, the method comprising:

• obtaining a measurement data set comprising a plurality of measurement entries comprising at least two measurements obtained at one data acquisition time from a patient before and after administration of the exogenous fluorescent agent, the at least two measurements comprising:
• a diffuse reflectance (DR) signal and a fluorescence emission (Flr) signal;
• generating at least one coefficient value for combining the DR and Flr signals from at least a portion of the measurement data set obtained prior to administration of the exogenous fluorescent agent to calculate a baseline intrinsic fluorescence (IF) signal;
• searching for the baseline IF signal having a minimum variance and constrained to a maximum drift over a predetermined time window;
• storing the at least one coefficient value of the baseline IF having the minimum variance and constrained to a maximum drift over the predetermined time window;
• creating a baseline-corrected agent IF signal by combining the stored at least one coefficient value with the Flr and DR signals collected after administration of the fluorescence agent;
• and
• monitoring the agent IF signal for each measurement data entry within a post-agent-administration portion of the measurement data set, whereby the fluorescence emission of the agent is determined with reduced sensitivity to the time-varying optical properties of the medium.

A method of monitoring time-varying fluorescence emitted from an exogenous fluorescent agent from within a diffuse reflecting medium with time-varying optical properties, the method comprising:

• providing a measurement data set comprising a plurality of measurement entries comprising at least four measurements obtained at one data acquisition time from a patient before and after administration of the exogenous fluorescent agent, the at least four measurements comprising:
• a diffuse reflectance signal at an emission wavelength of the fluorescent agent measured on a first detector that is not optically filtered (DRem,unfiltered);
• a diffuse reflectance signal at an emission wavelength of the fluorescent agent measured on a second detector that is optically filtered (DRem,filtered);
• a diffuse reflectance signal at an excitation wavelength of the fluorescent agent measured on the first detector (DRex);
• and
• a fluorescence emission signal (Flr) measured on the second detector;
• identifying a post-agent-administration portion of the measurement data set;
• transforming each DRex signal of each measurement data entry of the measurement data set to a DRex,corr signal by combining the DRex signal with the DRem,filtered, DRem,unfiltered, Flr signals and a heterogeneity factor to reduce a Flr contribution to the DRex signal;
• determining the heterogeneity factor by comparing the DRex,corr signal before and after the agent administration;
• transforming each Flr signal of each measurement data entry of the measurement data set to an intrinsic fluorescent (IF) signal representing a detected fluorescence intensity emitted by the exogenous fluorescent agent from within the diffuse reflecting medium, wherein transforming the Flr signal comprises combining the Flr, DRem,filtered and DRex,corr signals;
• monitoring the IF signal for each measurement data entry within the measurement data set, whereby the fluorescence emission of the agent is determined with reduced sensitivity to the time-varying optical properties of the medium.

A method of correcting baseline data in monitoring time-varying fluorescence emitted from an exogenous fluorescent agent, the method comprising:

• obtaining a measurement data set comprising a plurality of measurement entries comprising at least two measurements obtained at one data acquisition time from a patient before and after administration of the exogenous fluorescent agent, the at least two measurements comprising:
• a diffuse reflectance (DR) signal and a fluorescence emission (Flr) signal;
• generating at least one coefficient value for predicting a Flr baseline signal from the DR signal, wherein the at least one coefficient value is established using a correlation between the DR signal and Flr signal;
• storing the at least one coefficient value;
• calculating a predicted post-agent administered Flr signal using the at least one coefficient value;
• calculating an intrinsic fluorescence (IF) signal;
• creating a baseline-corrected agent IF signal by subtracting an auto-fluorescence contribution based on the predicted post-agent administer Flr signal from the calculated IF signal.