# US 10,311,567 B2 · Methods and systems for assessing healing of tissue > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,311,567 B2 - Document ID: US10311567B2 - Status: Granted - Kind: B2 - Application number: 15/224,088 - Filed: 2016-07-29 - Published: 2017-03-23 - Granted: 2019-06-04 - Earliest claimed: 2015-09-23 - Assignees: Novadaq Technologies ULC - Applicants: Novadaq Technologies ULC - Inventors: Lina Gurevich - Web page: https://patentgrep.com/patent/US10311567B2 ## CPC - G06T 7/0012: {Biomedical image inspection} - G16H 50/30: for calculating health indices; for individual health risk assessment - A61B 5/0071: {by measuring fluorescence emission} - A61B 5/0261: {using optical means, e.g. infrared light} - A61B 5/0275: using tracers, e.g. dye dilution - A61B 5/445: {Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore} - A61B 5/4842: {Monitoring progression or stage of a disease} - A61B 5/4848: {Monitoring or testing the effects of treatment, e.g. of medication} - A61B 5/7239: {using differentiation including higher order derivatives} - A61B 5/7275: {Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor} - A61B 2576/02: specially adapted for a particular organ or body part - G06T 2207/10064: Fluorescence image - G06T 2207/30088: Skin; Dermal - G16H 30/40: for processing medical images, e.g. editing - G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract Methods and systems for assessing tissue of a subject include receiving a time series of signal intensity data capturing the transit of an imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map. ## Claims ### Claim 1 A system for allowing assessment of tissue of a subject, the system comprising: one or more processors; and memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to: receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region; determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue. ### Claim 2 (depends on 1) The system of claim 1, wherein at least one calculation region is defined by one pixel or one voxel. ### Claim 3 (depends on 1) The system of claim 1, wherein the coefficient value characterizes a shape of the time-intensity curve. ### Claim 4 (depends on 3) The system of claim 3, wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof. ### Claim 5 (depends on 4) The system of claim 4, wherein the region of increasing slope of the time-intensity curve represents an arterial phase of the time-intensity curve and the region of decreasing slope of the time-intensity curve represents a venous phase of the time-intensity curve. ### Claim 6 (depends on 1) The system of claim 1, wherein the coefficient-derived image map is based on a correlation of each of the coefficient values with a respective pixel intensity. ### Claim 7 (depends on 1) The system of claim 1, wherein the coefficient-derived image map allows for, or provides information for use in, predictive assessment of healing of tissue of the subject. ### Claim 8 (depends on 1) The system of claim 1, further comprising a display, wherein the instructions cause the system to display the coefficient-derived image map on the display. ### Claim 9 (depends on 8) The system of claim 8, wherein the instructions cause the system to superimpose the coefficient-derived image map on an anatomical image of the tissue on the display. ### Claim 10 (depends on 1) The system of claim 1, further comprising (i) a light source that provides an excitation light to induce fluorescence emission from the imaging agent in the tissue; (ii) an image acquisition assembly that generates the time series of signal intensity data based on the fluorescence emission, (iii) or a combination thereof. ### Claim 11 (depends on 1) The system of claim 1, wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof. ### Claim 12 A method for use in medical imaging for assessing tissue of a subject, the method comprising: at a computer system including one or more processors and memory, receiving a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue. ### Claim 13 (depends on 12) The method of claim 12, wherein at least one calculation region is defined by one pixel or one voxel. ### Claim 14 (depends on 12) The method of claim 12, wherein the coefficient value characterizes a shape of the time-intensity curve. ### Claim 15 (depends on 14) The method of claim 14, wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof. ### Claim 16 (depends on 15) The method of claim 15, wherein the region of increasing slope of the time-intensity curve represents an arterial phase of the time-intensity curve and the region of decreasing slope of the time-intensity curve represents a venous phase of the time-intensity curve. ### Claim 17 (depends on 12) The method of claim 12, wherein converting the coefficient values into a coefficient-derived image map comprises correlating each coefficient value with an intensity value. ### Claim 18 (depends on 12) The method of claim 12, further comprising displaying the coefficient-derived image map on a display. ### Claim 19 (depends on 18) The method of claim 18, further comprising superimposing the coefficient-derived image map on an anatomical image of the tissue on the display. ### Claim 20 (depends on 12) The method of claim 12, wherein the assessing of tissue of the subject is based at least in part on the coefficient-derived image map. ### Claim 21 (depends on 20) The method of claim 20, wherein the assessing of tissue of the subject comprises assessing a wound in the tissue, a peri-wound in the tissue, or a combination thereof. ### Claim 22 (depends on 21) The method of claim 21, wherein assessing the wound in the tissue, the peri-wound in the tissue, or the combination thereof comprises assessing a state of the tissue, a property of the tissue, a condition of the tissue, a healing status of the tissue, or a combination thereof. ### Claim 23 (depends on 20) The method of claim 20, wherein the assessing of tissue of the subject comprises assessing a healing status of a wound based on a heterogeneous pattern in the coefficient-derived image map. ### Claim 24 (depends on 20) The method of claim 20, wherein the assessing of tissue of the subject comprises generating a quantitative predictor of the progress of healing of tissue, efficacy of clinical intervention, or a combination thereof, based on at least a portion of the coefficient-derived image. ### Claim 25 (depends on 20) The method of claim 20, further comprising comparing a plurality of coefficient-derived image maps that are based on a plurality of time series of signal intensity data captured over time, and assessing progress of healing of tissue, efficacy of clinical intervention, or a combination thereof based on the comparison of the plurality of coefficient-derived image maps. ### Claim 26 (depends on 20) The method of claim 20, further comprising: determining, for each calculation region, a second coefficient value that is related to at least a second portion of the time-intensity curve corresponding to the calculation region; and converting the second coefficient values across the plurality of calculation regions into a second coefficient-derived image map. ### Claim 27 (depends on 26) The method of claim 26, wherein the first coefficient-derived image map is an arterial coefficient-derived image map and the second coefficient-derived image map is a venous coefficient-derived image map. ### Claim 28 (depends on 26) The method of claim 26, wherein the assessing of tissue of the subject comprises generating a quantitative predictor of the progress of healing of tissue, efficacy of clinical intervention, or a combination thereof, based on the first and second coefficient-derived image maps. ### Claim 29 (depends on 28) The method of claim 28, wherein generating a quantitative predictor comprises comparing the area of a first selected region in the first coefficient-derived image map to the area of a second selected region in the second coefficient-derived image map. ### Claim 30 (depends on 29) The method of claim 29, wherein the first and second selected regions represent an actual or suspected wound. ### Claim 31 (depends on 29) The method of claim 29, wherein comparing the area of the first selected region and the area of the second selected region comprises determining a ratio of the area of the first selected region and the second selected region. ### Claim 32 (depends on 12) The method of claim 12, further comprising generating the time series of signal intensity data using a fluorescence imaging system that captures transit of the imaging agent through tissue over a period of time. ### Claim 33 (depends on 12) The method of claim 12, wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof. ### Claim 34 (depends on 1) A kit comprising the system of claim 1 and an imaging agent. ### Claim 35 (depends on 34) The kit of claim 34, wherein the imaging agent comprises a fluorescence imaging agent. ### Claim 36 (depends on 35) The kit of claim 35, wherein the fluorescence imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof. ### Claim 37 (depends on 34) The kit of claim 34 further comprising a tangible non-transitory computer readable medium having computer-executable program code embedded thereon, the computer executable program code providing instructions for causing one or more processors, when executing the instructions, to perform the method of receiving a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map. ### Claim 38 (depends on 37) The kit of claim 37 further comprising instructions for installing the computer-executable program code. ### Claim 39 A method for visualizing transit of an imaging agent through tissue of a subject, the method comprising: at a computer system including one or more processors and memory, receiving a time series of signal intensity data capturing the transit of the imaging agent through the tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue. ### Claim 40 (depends on 39) The method of claim 39, wherein at least one calculation region is defined by one pixel or one voxel. ### Claim 41 (depends on 39) The method of claim 39, wherein the coefficient value characterizes a shape of the time-intensity curve. ### Claim 42 (depends on 41) The method of claim 41, wherein the coefficient value characterizes a region of increasing slope of the time-intensity curve, a region of decreasing slope of the time-intensity curve, or a combination thereof. ### Claim 43 (depends on 39) The method of claim 39, further comprising displaying the coefficient-derived image map on a display. ### Claim 44 (depends on 43) The method of claim 43, wherein the coefficient-derived image map is a still image. ### Claim 45 (depends on 43) The method of claim 43, further comprising superimposing the coefficient-derived image map on an anatomical image of the tissue on the display. ### Claim 46 A system for allowing assessment of tissue of a subject, the system comprising: one or more processors; and memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to: receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region; determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of an actual or suspected wound. ### Claim 47 A system for allowing assessment of tissue of a subject, the system comprising: one or more processors; and memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to: receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region; determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein the assessing of tissue of the subject is based at least in part on the coefficient-derived image map; and wherein the assessing of tissue of the subject comprises assessing a wound in the tissue, a peri-wound in the tissue, or a combination thereof. ### Claim 48 A kit comprising: a system for allowing assessment of tissue of a subject, the system comprising: one or more processors; and memory having instructions stored thereon, the instructions, when executed by the one or more processors, cause the system to: receive a time series of signal intensity data capturing transit of an imaging agent through tissue over a period of time, wherein the time series of signal intensity data define a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to that calculation region; determine, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and convert the coefficient values across the plurality of calculation regions into a coefficient-derived image map; and an imaging agent, wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof. ### Claim 49 A method for use in medical imaging for assessing tissue of a subject, the method comprising: administering an imaging agent to the subject; at a computer system including one or more processors and memory, receiving a time series of signal intensity data capturing transit of the imaging agent through tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue. ### Claim 50 (depends on 49) The method of claim 49, wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof. ### Claim 51 (depends on 49) The method of claim 49, wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof. ### Claim 52 (depends on 49) The method of claim 49, wherein the imaging agent comprises indocyanine green. ### Claim 53 A method for visualizing transit of an imaging agent through tissue of a subject, the method comprising: administering the imaging agent to the subject; at a computer system including one or more processors and memory, receiving a time series of signal intensity data capturing the transit of the imaging agent through the tissue over a period of time, wherein the tissue comprises a plurality of calculation regions and wherein signal intensity in each calculation region over the period of time may be approximated by a time-intensity curve corresponding to the calculation region; determining, for each calculation region, a coefficient value that is related to at least a portion of the time-intensity curve corresponding to the calculation region; and converting the coefficient values across the plurality of calculation regions into a coefficient-derived image map; wherein a heterogeneous pattern in the coefficient-derived image map is indicative of actual or suspected changes in blood flow and perfusion in the tissue. ### Claim 54 (depends on 53) The method of claim 53, wherein the tissue comprises non-wound tissue, wound tissue, or a combination thereof. ### Claim 55 (depends on 53) The method of claim 53, wherein the imaging agent comprises indocyanine green, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, rose Bengal, trypan blue, fluoro-gold, green fluorescence protein, a flavin, methylene blue, porphysomes, cyanine dye, IRDDye800CW, CLR 1502 combined with a targeting ligand, OTL38 combined with a targeting ligand, or a combination thereof. ### Claim 56 (depends on 53) The method of claim 53, wherein the imaging agent comprises indocyanine green.