Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
  • A61B5/0062—Arrangements for scanning
  • A61B5/0066—Optical coherence imaging
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
  • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
  • A61B2560/02—Operational features
  • A61B2560/0223—Operational features of calibration, e.g. protocols for calibrating sensors

Definitions

• the present invention relates generally to methods for noninvasively measuring blood glucose or other analyte levels in a subject by measuring localized changes in light scattering from skin or other biological tissue.
• a method can include identifying tissue structures where the effect of blood glucose concentrations or levels are high, and targeting localized regions within the identified structures to measure blood glucose concentrations.
• IR is the intensity of light reflected from the skin
• Io is the intensity of the light illuminating the skin
• ⁇ a is the absorption coefficient of the skin at the specific wavelength of the light
• ⁇ s is the scattering coefficient of the skin at the specific wavelength of the light
• L is the total path traversed by the light. From this relationship, it can be seen that the intensity of the reflected light decays exponentially as either the absorption or the scattering by the tissue increases.
• the attenuation of light can be characterized by an attenuation coefficient, which is the sum of ⁇ s and ⁇ a .
• Glucose in its varying forms, is a major constituent of blood and IF.
• the variation in glucose levels in either blood or IF changes the refractive index of blood-perfused tissue, and thus the characteristic of scattering from such tissue. Further, glucose-induced changes to the refractive index are substantially greater than changes induced by variation of concentrations of other osmolytes in physiologically relevant ranges.
• NIR near-infrared
• blood glucose changes the scattering coefficient, ⁇ s , more than it changes the absorption coefficient, ⁇ a .
• optical scattering of the blood/IF and cell combination varies as the blood glucose level changes. Accordingly, there is the potential for non-invasive measurement of blood glucose levels.
• OCT optical coherence tomography
• OCT optical coherence tomography
• the key benefits of such a system in imaging applications include the ability to achieve a high resolution, e.g., better than 10 micrometers, and the ability to select the depth at which a sample can be imaged. For example, blood vessels beneath the surface of the skin can be imaged using such a system.
• a method for non-invasively measuring glucose levels in blood is presented. Specifically, changes in a scattering profile produced from an OCT-based monitor are related to changes in blood glucose levels by focusing on highly localized regions of the scattering profile where changes to the scattering profile induced by temperature, hydration, and other osmolytes are negligible.
• Glucose-induced changes to the scattering coefficient measured from these localized regions range between about 2% and about 20% per 1 mM/L or 18 mg/dL, with an average value of about 12% per 18 mg/dL. These percentage values are significantly higher than those measured using other methods. Additionally, within the localized regions, effects to the scattering coefficient induced by temperature, hydration, and other osmolytes are negligible compared to the effects of glucose, and, accordingly, can be ignored.
• the changes in the scattering profile can be related to changes in glucose concentrations by one or more mathematical algorithms.
• a method for noninvasively measuring blood glucose-levels in biological tissue includes the steps of scanning a two-dimensional area of skin with a monitor based on non-imaging optical coherence tomography, collecting cross-sectional depth measurement data continuously during the scanning step, and identifying at least one localized region within the cross-sectional depth measurement data, wherein the at least one localized region corresponds to a structure within the skin where glucose-induced changes to the cross-sectional depth measurement data are prominent. Further, the method includes the step of relating the cross-sectional depth measurement data to blood glucose levels.
• a method for calibrating OCT measurements using multiple light wavelengths is described to identify a tissue for measurement.
• At least two OCT scattering profiles can be obtained from light attenuated by a subject's tissue as a function of tissue depth.
• tissue include vascular tissue (e.g., a blood vessel wall), at least one component of blood, dermal tissue surrounding the vascular tissue, or some combination of the aforementioned types.
• the OCT scattering profiles can be obtained at different wavelengths of light such that the tissue can exhibit a different attenuation coefficient for each wavelength.
• the attenuation of light can be based at least in part on the presence of an analyte associated with the tissue (e.g., water or hemoglobin).
• the wavelengths can also be chosen such that the tissue has a different absorption coefficient at the two wavelengths.
• the wavelengths can also be chosen such that the scattering coefficient is larger than the absorption coefficient at the first selected wavelength, and optionally the absorption coefficient at the second wavelength is larger than the absorption coefficient at the first wavelength.
• a localized region e.g. , one or more depths
• OCT measurement calibration can be based upon a differential comparison of the two OCT scattering profiles.
• a blood glucose measurement e.g., some type of chemical blood analysis measurement
• can be associated with each of the OCT scattering profiles for calibrating other OCT measurements e.g., using the OCT scattering profiles and blood glucose measurements to make a calibration between attenuation coefficient and blood glucose concentration.
• the localized can have changing light attenuation coefficients based on the presence of blood glucose or other measurable analytes.
• the OCT scattering profiles can be normalized prior to differential comparison, with a depth corresponding to a tissue location for OCT measurement calibration depending upon a differential comparison of normalized OCT profiles (e.g., subtracting one normalized profile from another at corresponding depth locations). Normalization can be performed by dividing the scattering data of a respective OCT profile by the profile's respective peak intensity value. One or more extrema points in the differential comparison of normalized OCT profiles can be identified, and subsequently correlated with the depth of the tissue location or some other measure of the localized region corresponding with the tissue location.
• an offset location and an interval can define a localized region of an OCT scattering profile that can be correlated with a particular attenuation coefficient.
• the offset can correspond with a depth of a tissue location, and the interval can be determined from the offset location and the OCT scattering profile.
• the offset location and interval can be used to define the region of the OCT scattering profile in which a slope measurement can be correlated with the attenuation coefficient (or the scattering coefficient when absorption effects are small).
• Another exemplary embodiment is directed to a method of determining an absorption coefficient in OCT measurements using multiple light wavelengths.
• Two or more OCT scattering profiles can be obtained as a function of subject tissue depth at different wavelengths of light such that the tissue has a larger scattering coefficient than absorption coefficient at a first selected wavelength (e.g., the scattering coefficient being at least about 5 times greater than the absorption coefficient).
• a scattering coefficient can be determined from the first OCT scattering profile (e.g., by locating a slope in the first OCT scattering profile).
• An estimate of a scattering coefficient from the second OCT scattering profile can be obtained from the scattering coefficient of the first OCT scattering profile. Such an estimate can be obtained using scattering theory (e.g., Mie scattering).
• the absorption coefficient of the second OCT scattering profile can be determined using the estimate of the scattering coefficient at the second selected wavelength.
• a similar method can also be used to determine a scattering coefficient.
• Another method consistent with an embodiment of the invention is directed to calibrating OCT measurements using multiple light wavelengths. Two or more OCT measurements can be obtained as a function of time using different wavelengths of light for each measurement. The wavelengths can be chosen such that the tissue has a larger absorption coefficient at a first selected wavelength relative to a second. Such an absorption coefficient can also depend upon the presence of an analyte (e.g., water) in or around the tissue. One wavelength can also be chosen such that the scattering coefficient exceeds the absorption coefficient by at least about a factor of five.
• a first OCT measurement can be converted into an analyte measurement as a function of time.
• the analyte measurement can be used to calibrate a scattering coefficient measurement as a function of time.
• FIG. 1 illustrates a process flow of a method for measuring blood glucose
• FIG. 2 is a graphical illustration of a typical scattering cross section from a patch of human skin measured using an OCT-based monitor;
• FIG. 3 is an example of an intensity difference plot, according to an embodiment of the present invention.
• FIGS. 4 A and 4B are graphical illustrations in which scattering discontinuities are identified according to an embodiment of the present invention.
• FIG. 5 is a graphical illustration of an absorption effect of water at multiple wavelengths, according to an embodiment of the present invention.
• FIGS. 6 A and 6B are examples of scattering profiles at wavelengths of 1310 nanometers and 1440 nanometers, respectively, according to an embodiment of the present invention.
• FIG. 7 is a graphical illustration of a differential data set scattering profile, according to an embodiment of the present invention.
• a method for measuring blood glucose levels includes the step of utilizing an OCT-based sensor to take scattering cross-sectional depth measurements on a small area of biological tissue or skin.
• the OCT-based sensor can be anon-imaging system such as that described in detail in U.S. Application No. 10/916,236.
• a two-dimensional area of the skin can be scanned, preferably either in a circular pattern, e.g., with a radius no greater than about 2 mm, or in a filled disk or filled rectangular pattern where the pattern is drawn randomly.
• the OCT-based sensor scans the two-dimensional pattern continuously, the sensor continuously collects data corresponding to cross-sectional depth measurements within the biological tissue.
• Other embodiments can utilize an OCT-based sensor to obtain cross-sectional depth measurements with two-dimensional scanning.
• a method proposed for an OCT-based system includes scanning a two-dimensional pattern using a step-scan process, where the OCT-based system light beam picks a spot on the skin and takes multiple depth scans. The OCT-based system then averages these depth scans to reduce speckle, and moves on to another spot on the skin, takes multiple depth scans, and averages the depth scans. The OCT-based system repeats this process until a two-dimensional pattern has been made.
• the OCT-based monitor continuously scans an area of skin and continuously collects data. Using this method, fewer scans in less time are required to produce sufficient results. To further reduce speckle, a number of OCT scans can be averaged to produce an average OCT scan result. Thus, data associated with a particular OCT scan at a specific point in time is actually an averaged result of a group of OCT scans.
• an intensity profile, or scattering profile can be generated. Within the scattering profile, localized regions where changes to the scattering profile are dominated by changes in blood glucose can be identified. To locate these regions, a second-derivative plot can be generated, as disclosed in U.S. Provisional Application No.
• discontinuities in the scattering profile are exaggerated and easily visualized. These discontinuities represent structures in the skin where changes in blood glucose levels dominate the scattering profile. Within these highly localized regions, changes to the scattering profile induced by temperature, hydration, and other osmolytes, such as sodium, potassium, and urea, are very small compared to the effects of glucose, and therefore, can be ignored.
• the data of the scattering profile can be related to blood glucose levels using one or more mathematical algorithms such as, for example, an algorithm relating the slope of a portion of the OCT data curve to blood glucose levels, where the portion of the OCT data curve corresponds to a discontinuity in the scattering profile.
• mathematical algorithms such as, for example, an algorithm relating the slope of a portion of the OCT data curve to blood glucose levels, where the portion of the OCT data curve corresponds to a discontinuity in the scattering profile.
• the scattering profile can be related to blood glucose levels by utilizing a magnitude of the glucose-induced localized change, either using a straight peak intensity measurement or using an integrated intensity measurement where each region integrated corresponds to a localized region identified in the second-derivative plot.
• the scattering profile can be related to blood glucose levels using a change in full width at half- maximum measurement of one or more of the localized regions identified in the second- derivative plot.
• the scattering profile can be related to blood glucose levels using an angle computation, where the angle corresponds to apeak change in a localized region and an arbitrary depth.
• Another aspect of the embodiment of the present invention includes identifying localized regions of change in the scattering profile by utilizing an intensity difference plot (IDP), which is described in detail in U.S. Provisional Application No. 60/671,285.
• IDP intensity difference plot
• an IDP requires a significant change in glucose concentrations, such as, for example, the change caused by the subject ingesting food during the course of the testing time period while OCT scans are taken, one or more localized regions in the data curve that correspond to tissue structures where noticeable changes to the scattering profile were produced by changes in blood glucose levels can be identified. Once the localized regions are identified, the scattering profile from the localized regions can be related to blood glucose levels using the algorithms mentioned above.
• Yet another aspect of the embodiment of the present invention includes using a multiple- wavelength method to identify localized regions of the scattering profile that correspond to tissue and/or tissue structures, such as blood, blood vessels, or other tissue, where changes in the scattering profile due to presence of one or more analytes, such as blood glucose levels, are detectable.
• tissue and/or tissue structures such as blood, blood vessels, or other tissue
• changes in the scattering profile due to presence of one or more analytes, such as blood glucose levels are detectable.
• the term "wavelength” is used herein to define a region of the electromagnetic radiation spectrum that is distinguishable from other regions. While laser sources with narrow linewidths can be preferable, other lower resolution, or even broadband light sources, can also be used.
• the invention can be practiced with two wavelengths of light, one of which might be a multimode source spanning several nanometers, e.g., 1308-1312 nm or 1438-1442 nm.
• the OCT-based monitor can be constructed such that multiple wavelengths of light are employed to illuminate the skin.
• Light from multiple wavelengths is absorbed differently by different biological constituents, which differentially reduces the intensity of the scattered light.
• light reflected in and around tissue can be partially absorbed by a constituent for that wavelength.
• the constituent, in or around the tissue, for that wavelength absorbs some of the light according to the specific wavelength and/or the analyte level in or around the tissue.
• the differences in the scattering and absorption properties produced by multiple wavelengths interacting with different constituents provide for a determination of an optimal correlation between the scattered signal and a chosen analyte level. For example, light reflection and absorption in and around particular tissues and tissue structures can be correlated with the presence of glucose to provide a measurement of blood glucose levels.
• vascular tissue e.g., blood vessel walls
• blood and its components e.g., cells
• dermal tissue surround blood vessels, and any combination of the aforementioned tissues and/or tissue structures.
• the wavelengths can be chosen to provide an optimal contrast between the absorption and scattering effects of blood and other biological constituents, such as water. For instance, the wavelengths can be chosen to accentuate contrast regarding the presence of a particular analyte that is a signature of the presence of a tissue or tissue structure desired to be targeted by OCT measurements (e.g., water being a signature of the presence of blood perfused tissue).
• a first wavelength of light emitted from the OCT-based monitor can be chosen such that there is minimum absorption of the light by water compared to the scattering effect, which makes the absorption effects corresponding to water negligible, i.e., the total attenuation coefficient ( ⁇ « + ⁇ a ) is dominated by the scattering coefficient contribution.
• ⁇ s » ⁇ a when the scattering coefficient is at least about 5 times, or at least about 10 times, greater than - li the absorption coefficient.
• a second wavelength is chosen to provide peak absorption of light by water, then the difference in light attenuation between the two wavelengths can be used to indicate the position in depth of a blood perfused tissue structure, such as a blood vessel.
• three or more wavelengths of light can also be used to generate corresponding OCT profiles, with specific wavelength pairs utilized in a combination to generate a corresponding light attenuation difference.
• OCT scans are taken at two different wavelengths of light, where the first wavelength is chosen such that the scattering effects are dominant over absorption effects of water, and the second wavelength is chosen such that there is substantial absorption by water.
• the scattering data sets produced by scanning a two-dimensional area of the skin by the first and second wavelengths are normalized by finding the peak data point in each scattering data set and dividing all data points by the respective peak data point.
• each normalized scattering data set is now a set of decimal values with each peak data point having a value of 1.0.
• the normalized scattering data set of the second wavelength can be subtracted from the normalized scattering data set of the first wavelength to produce a differential scattering data set over the depth of the OCT signal, for a specific point in time.
• An “offset” is the depth of the OCT data curve at which to begin correlating the OCT data to the blood glucose levels.
• An “interval” is a certain portion or segment of the OCT data curve that is measured from the offset. For each OCT data curve there are numerous potential combinations or pairs of offsets and intervals.
• an offset depth
• the linear fit corresponds to an offset and interval combination where the slope of the offset and interval combination is highly correlated to blood glucose levels, i.e., the offset and interval can define the localized region of an OCT data curve in which an appropriate attenuation coefficient can be identified and correlated with a blood glucose level.
• each linear fit can identify a localized region where glucose-induced changes to the scattering profile are predominant.
• the attenuation coefficient reduces to a scattering coefficient.
• a anon-imaging OCT-based monitor or a "sensing" OCT-based monitor
• the OCT-based monitor continuously scans a two-dimensional area of skin, preferably scanning either a circle, a filled disk, or a filled rectangular pattern, where the filled pattern is drawn randomly.
• the monitor continuously collects cross-sectional depth measurements.
• continuously scanning a two-dimensional area of skin while continuously collecting data reduces speckle faster than previously known methods that use an OCT-based monitor. Additionally, fewer scans are required to average out speckle and thus, less time is required to take the scans.
• the cross-sectional depth measurements can be utilized to create a scattering profile in which the OCT data curve is plotted over time.
• FIG. 2 shows a scattering profile of light scattered from human skin as measured via an OCT-based monitor, according to an embodiment of the present invention. If an appropriate wavelength of light is chosen (e.g., around 1300 nanometers) where "an appropriate wavelength of light" is one in which the absorption coefficient of the light, ⁇ A , is small relative to the scattering coefficient, ⁇ s, of the light by the skin.
• a change in the OCT signal e.g., a change in the slope of a portion of an OCT profile
• the OCT data curve spikes at certain regions of the surface of the skin and then falls dramatically within the epidermis region of the skin.
• the OCT data curve also rises and slowly decreases within the dermis region as the depth of light in the skin increases.
• the slope of the OCT data curve can increase or decrease relative to the blood glucose level. That is, the slope of the OCT data curve will change in response to glucose level changes in very small defined regions. Because most blood vessels are located in the dermis region, it is this portion of the OCT data curve that provides data for measuring blood glucose levels. To identify this region, one or more of the graphs described below can be generated.
• an intensity difference plot can be generated to highlight one or more regions of the OCT data curve that correspond to tissue structures where glucose-induced changes are dominant.
• An example of an intensity difference plot is illustrated in FIG. 3.
• two OCT scans are selected and the difference in the OCT data between the selected two OCT scans is computed.
• the differential data can then be plotted to produce an IDP, as shown in FIG. 3. From the IDP, one or more zero-crossing points can be identified as well as localized extrema surrounding the zero-crossing points, respectively.
• the IDP in FIG. 3 has one zero-crossing point, which is located at a depth of about 225 microns.
• a local maximum data point is located at around 200 microns and a local minimum point is located at around 350 microns.
• the region of the localized extrema represents a highly localized region where glucose-induced changes to the scattering coefficient are the dominant effect within a tissue structure, and is represented in FIG. 3 by a shaded box.
• the highly localized region can be focused upon and data falling outside this region can be ignored. Within this region, effects due to temperature, hydration, and other osmolytes are negligible.
• the box can be expanded to include potential offsets within a variance amount of the localized extrema. For example, in FIG. 3, the range of potential offsets includes offsets from 175 microns to 400 microns.
• the scattering profile can be used to generate a second-derivative plot.
• discontinuities in the scattering profile represent structures in the skin where changes due to variations in blood-glucose levels are high relative to changes in the scattering profile induced by other analytes.
• the second- derivative plot enhances these discontinuities to help identify one or more highly localized regions where the scattering profile can be related to blood glucose levels.
• FIGS. 4 A and 4B graphically illustrate how a second-derivative plot enhances discontinuities in the scattering profile. In FIG. 4A, a scattering profile is plotted against the depth of the scanned area of skin.
• Discontinuities in the scattering profile are identified by circles in the graph, however, these discontinuities typically are difficult to visualize.
• a square of a second derivative of the scattering profile is plotted against the depth of the scanned area of skin.
• the discontinuities in the scattering profile are enhanced by the second derivative computation, while calculating the square value of the second derivative removes any negative values that can exist.
• the discontinuities correspond to structures in the skin where changes in blood glucose levels are dominant, such as, for example, blood vessels.
• the scattering data corresponding to the identified localized regions can then be related to blood glucose levels.
• Another aspect of the embodiment includes utilizing multiple wavelengths to identify tissue and/or tissue structures with a high degree of hydration or water content due to blood perfusion, such as blood vessels where changes in blood glucose levels are prevalent, at step S 103.
• the localized regions of the scattering profile that correspond to these tissue structures then correlate well to blood glucose levels.
• the OCT-based monitor can utilize multiple wavelengths of light, where one wavelength is chosen that produces a minimum absorption of light by water in the interstitial fluid, and another wavelength is chosen that provides a substantial absorption of light by water.
• FIG. 5 illustrates the absorption of light by water at different wavelengths.
• the differential scattering data set produced from the OCT data of the two wavelengths can be used to determine tissue structures where hydration is high, such as a blood vessel.
• tissue structures where hydration is high such as a blood vessel.
• other analytes indicative of a tissue or tissue structure can also be detected by the choice of appropriate light wavelengths.
• hemoglobin has a peak absorption at 660 nm when deoxygenated and 940 nm when oxygenated. Accordingly, either of these wavelengths can be useful to detect oxygen levels in tissue.
• a measured analyte e.g., blood glucose or hemoglobin
• the difference in intensity of the two wavelengths is due mostly to the presence of water or some other analyte indicative of the presence of a blood vessel or other tissue structure.
• the scattering profiles for each wavelength at a particular point in time can be plotted, as shown in FIGS. 6A and 6B, which represent exemplary scattering profiles for first and second wavelengths of 1310nm and 1440 nm, respectively.
• the scattering data set for each wavelength has been normalized using the respective peak intensity value.
• me peak intensity value for each scattering data set is 1.0, and each data point around the peak is less than 1.0. Because the sensitivity of the OCT-based monitor is different at the two wavelengths, the scattering profiles of the two wavelengths can not be compared directly. Normalization of the scattering data sets allows direct comparison of the scattering data sets from the two wavelengths.
• the normalized scattering data set of the second wavelength can be subtracted from the normalized scattering data set of the first wavelength to produce a differential scattering data set.
• a differential data curve plot can be produced, as shown in FIG. 7.
• the profile of the differential data curve suggests one or more offset and interval pairs that correspond to localized regions of the scattering profile where variations in blood glucose levels are the predominant effect.
• One or more peak data points identified in the differential data curve suggests one or more depths or offsets at which to begin correlating the OCT data to blood glucose levels.
• one or more intervals can be identified by choosing one or more data points on either side of the peak data point(s).
• the combination of the offset(s) and the one or more intervals produces offset and interval pairs that can be applied to the scattering profile produced by the first wavelength, e.g., 1310 nm, to identify localized regions where glucose-induced effects to the scattering profile are predominant.
• one or more algorithms can be used to relate the scattering profile to blood glucose levels, at step S 104.
• the slope of portions or segments of the IDP data curve that correspond to the localized regions can be used to compute predicted blood glucose levels, as described in U.S. Provisional Application 60/671,285.
• the scattering profile can be related to blood glucose levels using a magnitude value of a localized change, either using a straight peak intensity measurement or an integrated intensity measurement using the entire localized region. Another option is to use a change in the full- width at half-maximum measurement of one or more of the localized regions, at step S 104c.
• tissue or tissue structures for glucose monitoring is not intended to limit the use of the technique to the particular application exemplified in the description. Indeed, beyond identifying the presence of water or hydration content of blood vessels, other analytes such as hemoglobin at varying oxygen content can also be utilized as a signature of a particular tissue or tissue structure (e.g., oxygenated tissue). As well, the types of tissue and tissue structures to which multiple wavelength OCT measurements can be used are not limited to blood vessels but can include other vascular tissue, blood (or particular constituents thereof such as cells), dermal tissue surround vascular tissue, and combinations of such exemplary tissues and tissue structures.
• the technique is not limited to detecting blood glucose, but can be used to diagnose other conditions unrelated to blood glucose.
• the technique of using of multiple wavelengths to determine tissue hydration levels can be applied in a variety of contexts including assessment and/or monitoring of congestive heart failure, management of fluid therapy for shock or surgery, management of fluid load in dialysis patients (e.g., peritoneal dialysis or hemodialysis), and management of tissue hydration in pulmonary disease and hypertension.
• multiple wavelength OCT measurements can be used to monitoring clotting factors in blood.
• the scattering coefficient of blood is affected by hydration
• use of the multiple wavelengths allows one to determine the contribution to the scattering coefficient that is substantially hydration independent by comparing scattering coefficients at wavelengths that absorb water strongly and weakly.
• the scattering coefficient at low water absorbing wavelengths can be related to the viscosity, and eventually the clotting factors of the blood. Such a measurement could be useful in post-surgical monitoring of patients who are administered blood thinning agents.
• the scattering coefficient at low water absorbing wavelengths can also be adjusted using the measurements at higher water absorbing wavelengths.
• actual samples of the measured analyte can be utilized to aid in calibration (e.g., the use of blood glucose samples as described with reference to glucose monitoring herein).
• multiple wavelength OCT measurements can be utilized to provide an improved estimate of a scattering coefficient or an absorption coefficient from tissue measurements.
• Such an aspect can be utilized in conjunction with any of the potential applications of the present invention such as determining the viscosity of blood.
• the following description is with reference to estimating an absorption coefficient, though estimates of a scattering coefficient can also be obtained under analogously consistent conditions.
• a pair of OCT scattering profiles are obtained, each profile corresponding to a measurement at a particular wavelength of light.
• the profiles can be obtained by scanning a two-dimensional area of skin to obtain measurements at a number of cross-sectional depths.
• one profile is obtained using light with a wavelength of about 1310 nm and another profile is obtained using 1440 nm light.
• the intensity of the reflected light at 1310 nm can be approximated by the following equation:
• IR is the reflected light intensity at 1310 nm
• I 0 is the initial light intensity at 1310 nm
• L is the total light pathlength
• Us 1310 is the scattering coefficient of the tissue at 1310 nm
• (J 3 1310 is the absorption coefficient of the tissue at 1310 nm.
• a wavelength can be selected such that one of the scattering or absorption coefficients is stronger than the other to the extent that the contribution of the weaker can be ignored (e.g., when one contribution is at least about 5 times greater or at least about 10 times greater than the other).
• the scattering coefficient ⁇ s 1310 is stronger than the absorption coefficient ⁇ a 1310 such that the contribution from ⁇ a mo can be ignored; this allows the scattering coefficient ⁇ s 1310 to be determined. Accordingly, a plot of In(WI 0 ) versus depth can yield a line with a slope that can be equated with ⁇ s 1310 .
• the scattering coefficient at 1310 nm ⁇ s 1310 can be used to provide a measure of the scattering coefficient at 1440 nm, ⁇ s 1440 .
• Various scattering theories can be used to relate the scattering coefficients at the two different wavelengths. For example, under Mie scattering, (0.7) ⁇ s 1310 - U 3 1440 . Using this estimate for ⁇ s 1440 , an estimate of the absorption coefficient at 1440 nm can be found using:
• IR is the reflected light intensity at 1440 nm
• I 0 is the initial light intensity at 1440 nm
• L is the total light pathlength
• ⁇ s 1440 is the scattering coefficient of the tissue at 1440 nm
• ⁇ a 1440 is the absorption coefficient of the tissue at 1440 nm.
• the OCT profile at 1440 nm, along with the estimated scattering coefficient ⁇ s 1440 , can allow one to i • 1440 determine ⁇ a
• the outlined technique can also be used to determine scattering coefficients when a scattering profile utilizes a wavelength in which an absorption coefficient dominates (e.g., an absorption coefficient is measured using a wavelength where absorption dominates attenuation, followed by estimating an absorption coefficient at a second wavelength and determining the scattering coefficient at the second wavelength).
• the technique can also be applied with respect to other analytes besides water (e.g., hemoglobin) when appropriate wavelengths of light are chosen.
• water e.g., hemoglobin
• the use of multiple wavelengths can also provide an additional sensor calibration technique.
• the scattering coefficient of a first wavelength OCT measurement can drift even though the glucose concentration remains static because of the change in the scattering coefficient due to hydration changes.
• a second wavelength in which the wavelength is selected such that the resulting scattering profile tracks hydration changes e.g., the absorption coefficient at the second wavelength is high for water, and much higher relative to the absorption coefficient at the first wavelength
• this drift can be compensated for and the OCT sensor can maintain calibration.
• other analytes that can effect scattering coefficient measurements can also be compensated for using this technique.

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