System and method for assessing cellular metabolic activity

A system for in-vivo optical assessment of cellular metabolic activity, comprising:

• an optical radiation source for illuminating at least one cell in-vivo so as to cause multi-photon excitation of any of NAD (P) H and a flavin in said at least one cell,
• a detector configured to detect fluorescent radiation emitted by any of the excited NAD (P) H and the excited flavin and generate one or more detector signals indicative of the detected fluorescent radiation;
• and
• an analyzer comprising a processor configured to receive the one or more detector signals and operate on the one or more detector signals to determine:
• (1) an intensity of fluorescent radiation emitted by any of said excited NAD(P)H and said excited flavin,
• (2) a parameter associated with a fluorescence lifetime of any of the excited NAD(P)H and the excited flavin, and
• (3) a mitochondrial clustering parameter associated with the at least one cell, and
• wherein the analyzer is further configured to use a combination of said mitochondrial clustering parameter with at least one of an optical redox ratio of NAD(P)H and flavin computed based on said intensities of emitted fluorescent radiation and said parameter associated with the fluorescence lifetime to assess at least one metabolic process in said at least one cell,
• wherein the at least one metabolic process is selected from the group consisting of glycolysis, oxidative phosphorylation, glutaminolysis, fatty acid oxidation, extrinsic and intrinsic mitochondrial uncoupling, and fatty acid synthesis.

A system for in-vivo optical assessment of cellular metabolic activity, comprising:

• an optical radiation source for illuminating at least one cell in-vivo so as to cause multi-photon excitation of at least two metabolic cofactors associated with mitochondria of said at least one cell, wherein the at least two metabolic cofactors emit fluorescent radiation in response to the excitation, and wherein at least one of said at least two metabolic cofactors comprises any of NAD(P)H and a flavin;
• a detector configured to detect the emitted fluorescent radiation and generate one or more detector signals indicative of the detected fluorescent radiation;
• and
• an analyzer comprising a processor configured to receive the one or more detector signals and operate on the one or more detector signals to determine:
• (1) an optical redox ratio based on fluorescent radiation intensity associated with fluorescent radiation emitted by said excited at least two metabolic cofactors,
• (2) a parameter associated with a fluorescence lifetime of the at least one of said at least two metabolic cofactors, and
• (3) a mitochondrial clustering parameter associated with the at least one cell, and
• wherein the analyzer is further configured to use a combination of said mitochondrial clustering parameter with said optical redox ratio and said parameter associated with the fluorescence lifetime to assess at least one metabolic process in said at least one cell.

A system for optical assessment of cellular metabolic activity, comprising:

• an optical radiation source for illuminating at least one cell so as to cause multi-photon excitation of at least two metabolic cofactors in said at least one cell, wherein the at least two metabolic cofactors emit fluorescent radiation in response to the excitation, and wherein the at least two metabolic cofactors comprise NAD(P)H and a flavin,
• a detector configured to detect the emitted fluorescent radiation and generate one or more detector signals indicative of the detected fluorescent radiation;
• and
• an analyzer comprising a processor configured to receive the one or more detector signals and operate on the one or more detector signals to determine:
• (1) an intensity of the emitted fluorescent radiation,
• (2) a parameter associated with fluorescence lifetime of at least one of said at least two metabolic cofactors, and
• (3) a parameter indicative of mitochondrial clustering in the at least one cell, and
• wherein the analyzer is further configured to use a combination of the fluorescent radiation intensity, the parameter associated with the fluorescence lifetime and said parameter indicative of mitochondrial clustering to assess at least one cellular metabolic process in the at least one cell, wherein the at least one cellular metabolic process is selected from the group consisting of glycolysis, oxidative phosphorylation, glutaminolysis, fatty acid oxidation, extrinsic and intrinsic mitochondrial uncoupling, and fatty acid synthesis,
• wherein the analyzer is further configured to correlate an increase in the mitochondrial clustering parameter with enhanced glycolysis, enhanced fatty acid synthesis, enhanced fatty acid oxidation, or mitochondrial uncoupling, and
• wherein the analyzer is further configured to correlate an increase in the mitochondrial clustering parameter combined with a decrease in an optical redox ratio of the NAD(P)H relative to the flavin computed based on the intensity of the emitted fluorescent radiation and a decrease in NAD(P)H fluorescence lifetime with enhanced glycolysis.

A system for in-vivo optical assessment of a cellular metabolic activity, comprising:

• an optical radiation source for illuminating at least one cell in-vivo so as to cause multi-photon excitation of at least one metabolic cofactor,
• a detector configured to detect fluorescent radiation emitted by the excited at least one metabolic cofactor and generate one or more detector signals indicative of the detected fluorescent radiation;
• and
• an analyzer comprising a processor configured to receive the one or more detector signals and operate on the one or more detector signals to determine fluorescence intensity emitted by the at least one metabolic cofactor, fluorescence lifetime of the at least one metabolic cofactor, and mitochondrial clustering within the at least one cell and to identify changes in one or more metabolic processes selected from the group consisting of glycolysis, glutaminolysis, extrinsic and intrinsic mitochondrial uncoupling, fatty acid oxidation and synthesis, and oxidative phosphorylation based on at least two of said fluorescence intensity, said fluorescence lifetime and said mitochondrial clustering.