System, method and article for normalization and enhancement of tissue images

Abstract

In medical imaging, a fiducial marker facilitates tissue image correlation that allows for image analysis, normalization and correction of the optical exposure and spectral and spatial distribution in order to compensate for the surface reflections, sub surface tissue interactions and spatial orientation of the excitation and imaging axes to the subject tissue. Using a cross comparison, clinicians can model tissue image data in different forms in order to reference and compare data from various spectral components and or from different images. This may enhance human interpretation between images including the variations between images even when the spectral, spatial and optical conditions or the image resolution or sensitivity are compromised. Such may be used to assess cosmetic, moisturizing, therapeutic materials and treatments.

I claim: 
     
         1 . A method of operating a system for use in tissue analysis, the method comprising:
 comparing by at least one processor an appearance of at least one shape of at least a first fiducial marker in a first digital image of a portion of a tissue to at least one defined actual shape of the fiducial marker;   comparing by the at least one processor an appearance of each of a plurality of sections of the fiducial marker in the first digital image to respective ones of defined sections of the fiducial marker including a number of tissue phantoms each having a respective spectral characteristic that matches a respective spectral characteristic of tissue of a type represented in the first digital image; and   at least one of correlating, normalizing, or correcting at least the first digital image, based at least in part on the comparisons.   
     
     
         2 . The method of  claim 1  wherein the fiducial marker includes a scatter layer that overlies at least some of the tissue phantoms and which simulates an optical character of the type of tissue represented in the first digital image, and wherein comparing an appearance of each of a plurality of sections of the fiducial marker in the first digital image to respective ones of defined sections of the fiducial marker includes comparing the appearance of the sections which include the tissue phantoms which are overlaid by the scatter layer with a number of defined sections which include the tissue phantoms overlaid by the scatter layer. 
     
     
         3 . The method of  claim 2  wherein a number of sections of the fiducial marker include a respective color including at least one of black, white, a plurality of different shades of grey, and a plurality of additional colors that are not black, white or grey, and wherein comparing an appearance of each of a plurality of sections of the fiducial marker in the first digital image to respective ones of defined sections of the fiducial marker includes comparing the appearance of the sections which include the respective colors with respective ones of a defined set of respective colors. 
     
     
         4 . The method of  claim 1 , further comprising:
 storing to at least one nontransitory storage medium the digital image as a multi-layer image file, including a first digital image layer that stores and at least a second digital image layer that stores image metadata.   
     
     
         5 . The method of  claim 4 , further comprising:
 storing to a diagnostic layer of the digital image on the nontransitory storage medium information indicative of at least one of an NADH fluorescence, a collagen fluorescence, a physical scattering of light from the tissue at a number of physical layers of the tissue due to tissue density, a spectral distribution due to a size of a cell nuclei, and a hemoglobin absorption due to increased blood flow or oxygenation or registering a number of subsequent digital images in spatial and optical relationship by the at least one processor, and   comparing the first and subsequent digital images on a layer by layer basis by the at least one processor.   
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , further comprising:
 (i) referencing by the at least one processor at least one of spectral changes or optical density at specific coordinates in the first digital image to allow later comparison to changes in a number of subsequent digital images of the region of interest; or (ii)   comparing by the at least one processor a number of ratios of respective radiant spectral intensity of a number of wavelengths or wavebands in the first digital image.   
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 7 , further comprising:
 comparing by the at least one processor a number of ratios of respective radiant spectral intensity of a number of wavelengths or wavebands in at least one subsequent digital image.   
     
     
         10 . The method of  claim 1  wherein normalizing includes normalizing a plurality of digital images including the first digital image by measuring a difference of a spectral distribution between an optical character of the tissue in combination with the fiducial marker, where a monotonicity of a number of defined spectral relationships is proximate or exceeds a limit of a normal spectral distribution. 
     
     
         11 . The method of  claim 1 , further comprising:
 (i) establishing a subject specific baseline by the at least one processor which is specific to an individual; and wherein the normalizing is based at least in part on the subject specific baseline the first digital image and a plurality of sequential digital images, the sequential digital images sequentially captured at various times following a capture of the first digital image; or (ii) generating a probability index by the at least one processor based on a combination of distributed properties of a number of variables including a normalization, an exposure correction, a geometric correlation, an optical spectroscopic correction, a signal to noise characterization, or a defined diagnostic protocol.   
     
     
         12 . The method of  claim 11 , further comprising:
 determining a number of differences in the region of interest as the region of interest appears between the normalized digital images including the first digital image and the plurality of sequential digital images, by the at least one processor, as part of a tissue analysis.   
     
     
         13 . The method of  claim 12  wherein determining a number of differences includes (i) determining any morphological changes of the region of interest as the region of interest appears between the digital images as part of the determination of the differences in the region of interest as the region of interest appears between the normalized digital images including the first digital image and the plurality of sequential digital images; (ii) assessing any change in at least one of a level of skin hydration, a total number of wrinkles or a size of at least one wrinkle, or a total number of blemishes or a size of at least one blemish; or (iii) assessing at least one of a level of hydration or a level of blood flow between the first digital image and at least one subsequent digital image, where the first digital image represents the region of interest prior to a first application of a cosmetic, a moisturizer, a therapeutic or a therapeutic treatment and the at least one subsequent digital image represents the region of interest after the first application of the cosmetic, the moisturizer, the therapeutic or the therapeutic treatment. 
     
     
         14 .- 15 . (canceled) 
     
     
         16 . The method of  claim 1  wherein (i) normalizing includes normalizing at least the first digital image based at least in part on a spectral marker of hemoglobin and a spectral marker of collagen; (ii) the instructions further cause the at least one processor to generate a digital model that geometrically represents the region of interest in three dimensions based on spatial and spectral data from the digital images; or (ii) correcting includes correcting at least the first digital image based at least in part on color correction information. 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The method of claim  18 , further comprising:
 (i) associating at least one of multispectral data or image timeline data to the digital model that geometrically represents the region of interest in three dimensions by the at least one processor, or (ii) rectifying the tissue by the at least one processor with a three dimensional map of at least a portion of a body which combines a set of three dimensional model probabilities with a correlation of a set of coordinate locations, a set of spectral effects and a set of complex interactions.   
     
     
         20 .- 21 . (canceled) 
     
     
         22 . The method of claim  21 , further comprising:
 generating by the at least one processor a digital multidimensional lesion map that tracks a set of pixel characteristics in at least the first digital image including at least one of a surface, a sub-surface, other layers or a depth characteristic of the tissue as determined from a spectral analysis of the tissue as represented in at least the first digital image.   
     
     
         23 . The method of claim  21  wherein correcting further includes correcting for (i) spectral effects in the tissue represented in at least the first digital image which spectral effects are due to interactions of light absorption, reflectance and fluorescence, and to cross reference and compare a number of spatial and a number of spectral components specified by at least one of a digital model of tissue image data or another digital image to generate the digital three dimensional model of the region of interest; or (ii) differences in spatial orientation of at least one of an excitation axis or an imaging axis of a tissue imaging system in Cartesian space. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 1 , further comprising:
 (i) registering each of a plurality of digital images of the tissue by the at least one processor, including the first digital image, based at least in part on a variation between image layer coordinates in a temporal sequence of a plurality of digital images of the tissue; (ii) generating by the at least one processor an analysis comparison of layers in at least the first digital image as a histogram; or (iii) generating by the at least one processor a probability distribution of a tissue being abnormal.   
     
     
         26 .- 27 . (canceled) 
     
     
         28 . The method of  claim 25  wherein generating a probability distribution of a tissue being abnormal includes generating the probability distribution of the tissue being abnormal based at least in part on a comparison of an optical density to a percentage of optical spectra that is attributable to collagen. 
     
     
         29 . The method of  claim 1  wherein a probability distribution of a tissue being abnormal includes generating the probability distribution with a probability index that weights at least some digital images according to at least one of a diagnostic value or a comparative amount of change between spectra. 
     
     
         30 . A system for use in tissue analysis, the system comprising:
 at least one processor; and   at least one nontransitory storage medium that stores processor executable instructions which when executed cause the at least one processor to:   compare an appearance of at least one shape of at least a first fiducial marker in a first digital image of a portion of a tissue to at least one defined actual shape of the fiducial marker;   compare an appearance of each of a plurality of sections of the fiducial marker in the first digital image to respective ones of defined sections of the fiducial marker including a number of tissue phantoms each having a respective spectral characteristic that matches a respective spectral characteristic of tissue of a type represented in the first digital image; and   at least one of correlate, normalize, or correct at least the first digital image, based at least in part on the comparisons.   
     
     
         31 .- 58 . (canceled) 
     
     
         59 . A fiducial marker for use in tissue imaging, comprising:
 a substrate having a defined profile and bearing a plurality of sections having respective wavelength selective absorption, reflectance or florescence characteristic, at least a first number of the sections form a color chart of a plurality of different colors and at least a second number of the sections are optical phantoms that match respective ones of a number of spectral characteristics of living tissue.   
     
     
         60 .- 86 . (canceled)