WO2000016692A1 - Mesure non invasive de la glycemie fondee sur des observations optoelectroniques de l'oeil - Google Patents

Mesure non invasive de la glycemie fondee sur des observations optoelectroniques de l'oeil Download PDF

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Publication number
WO2000016692A1
WO2000016692A1 PCT/US1999/021680 US9921680W WO0016692A1 WO 2000016692 A1 WO2000016692 A1 WO 2000016692A1 US 9921680 W US9921680 W US 9921680W WO 0016692 A1 WO0016692 A1 WO 0016692A1
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WIPO (PCT)
Prior art keywords
electromagnetic
measuring
radiation
eye
pupil
Prior art date
Application number
PCT/US1999/021680
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English (en)
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WO2000016692A9 (fr
Inventor
Walter K. Proniewicz
Dale Winther
Original Assignee
Proniewicz Walter K
Dale Winther
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Proniewicz Walter K, Dale Winther filed Critical Proniewicz Walter K
Priority to AU61536/99A priority Critical patent/AU6153699A/en
Priority to PCT/US2000/001698 priority patent/WO2001022061A1/fr
Priority to JP2001525185A priority patent/JP2003524153A/ja
Priority to KR1020027003472A priority patent/KR20020070964A/ko
Priority to EP00909963A priority patent/EP1216409A1/fr
Priority to CA002390520A priority patent/CA2390520A1/fr
Priority to AU32135/00A priority patent/AU3213500A/en
Priority to US09/489,593 priority patent/US6853854B1/en
Publication of WO2000016692A1 publication Critical patent/WO2000016692A1/fr
Publication of WO2000016692A9 publication Critical patent/WO2000016692A9/fr
Priority to US10/783,671 priority patent/US20050171416A1/en
Priority to US11/552,100 priority patent/US7869848B2/en
Priority to JP2010189230A priority patent/JP2010284552A/ja
Priority to JP2010189026A priority patent/JP2010276616A/ja

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Classifications

    • 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
    • A61B5/1455—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 using optical sensors, e.g. spectral photometrical oximeters
    • 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
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0004—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by the type of physiological signal transmitted
    • A61B5/0013—Medical image data

Definitions

  • This invention relates generally to nonmvasive blood testing; and more particularly to optoelectronic determination of glucose concentration in the blood, also called “blood sugar” . Optoelectronic determination of glaucoma overpressure w th:n the eye is also introduced.
  • blood testing is an invasive procedure, sometimes requiring blood to be drawn several times a day. This is true in particular for sufferers of diabetes — including one of the present inventors .
  • Some of these devices are nominally subject to plus- cr-minus twenty- or thirty-percent error, and it is com- monplace for two such devices to report blood-sugar values differing by 80 ⁇ g/dL and more — even when the reported values are both well below 200 mg/dL.
  • the present invention introduces such improvement.
  • the invention has several facets or aspects which are usable independently — although for greatest enjoyment of their ben- e its we prefer to use them together, and although some of them do have some elements in common.
  • the invention is noninvasive apparatus for measuring blood-sugar concentration m a living body by measuring electromagnetic-radiation reflectivity from the body.
  • the apparatus includes some means for directing electromagnetic radiation to such body. For purposes of breadth and gener- ality in discussion of the invention we shall refer to these means simply as the "directing means".
  • the apparatus includes some means for receiving and measuring electromagnetic radiation reflected from sucr. body substantially without spectral analysis of the reflected electromagnetic radiation. Again for generality and breadth we shall call these the "receiving and measuring means" .
  • this facet of the invention entirely eliminates need for piercing the body or otherwise obtaining blood samples, and so avoids the discomfort, fear and other detriments discussed above.
  • this aspect of the invention is advantageous in that it requires no elaborate spectral modulation, or multiple detectors for different wavelength regions, or dispersive elements — such as re- quired to perform spectral analysis.
  • the apparatus is remarkably simple, economical and reliable.
  • the directing means direct electromagnetic radiation to an eye of the body; and the receiving and measuring means include some means for receiving and measuring electromagnetic radiation reflected from the eye.
  • the receiving and measuring means comprise a monochrome detector array — and in this case still more preferably the monochrome detector array comprises a black-and-white charge-coupled-detector (CCD) camera.
  • the receiving and measur- 5 mg means include a digital processor for analyzing signals rom the CCD camera .
  • Such a processor is desirable for analyzing signals representative of quantities of the reflected electromagnetic radiation.
  • the digital processor be part of a personal computer, and the blood glucose level is reported on a monitor screen of the computer.
  • the apparatus be a handheld portable unit, that the unit include 5 reporting means for indicating the blood glucose level, and that the digital processor be part of the handheld portable unit.
  • the reporting means include an LCD unit for visually indicating the blood glucose level.
  • the receiving and o measuring means include some means for detecting change in level of the reflected electromagnetic radiation, and relating said change to blood-glucose concentration.
  • the receiving and measuring means include some means for detecting change in level of the reflected 5 electromagnetic radiation — and also some means for reporting glucose concentration that varies substantially monoton- lcally with reflected-electromagnetic-radiation level.
  • the detecting means mclude some means for responding to reflected visible light — and, m this case, particularly to light in the yellow or yellow-green portion of the spectrum, or both.
  • the apparatus has been described as operating substantially without spectral analysis, this is not intended to imply that the apparatus is necessarily entirely unable to differentiate between spectral regions.
  • the apparatus includes some means for eliminating response to some particular electromagnetic-ra- diation band — e. ⁇ . the red or infrared, or both.
  • the means for receiving and measuring substantially without spectral analysis preferably do take into account a reverse signal response in the red or infrared, or both.
  • the invention is a nonmvasive apparatus for measuring blood-sugar concentration in a living body by measuring electromagnetic-radiation reflectivity from the body.
  • the apparatus includes a self-contained case.
  • the entire invention is capable of reduction to be carried within a self-con- taine ⁇ case
  • the many benefits of nonmvasive measurement can be enjoyed in a unit that need not take the form of a machme only suited for use a medical facility. Rather, the invention can be implemented in a machine suited for patients' use at home, or at an ordinary office or other business — or in cars, restaurants, etc.
  • the second major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics.
  • the case is fully portable. Also m this instance preferably the case fits the palm of ⁇ normal-size adult's hand.
  • the invention is a nonmvasive apparatus for measuring blood-sugar concentration in a living body by measuring electromagnetic-radiation reflectivity from an eye of the body.
  • the apparatus includes some means for directing electromagnetic radiation to an iris of such eye. It also includes some means for receiving and measuring electromagnetic radiation reflected from such iris.
  • a programmed digital processor that analyzes the measured reflected radiation and computing blood-sugar concentration therefrom — and in particular uses a reflection of the electromagnetic-radiation source, from the eye, as a peak amplitude point for image alignment.
  • the foregoing may represent a description or definition of the third aspect or facet of the invention in its broad- est or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
  • the eye is generally available for optoelectronic measurements without the subject' s disrobing or any other great inconvenience.
  • condition of the blood the eye s generally particularly rapid in its response to or tracking of the condition of the blood in other critical parts of the body — particularly the brain.
  • the receiving and measuring means also include some means for receiving and measuring electromagnetic radiation from a pupil of the eye.
  • This preference facilitates determination of a baseline dark level, or of an illumination level provided by the electromagnetic-radiation directing means, or both.
  • the invention is a blood-glucose measuring method.
  • the method includes the step of imaging forward surfaces of a person' s eye on an electronic camera. It also includes digitizing resultant image signals from the camera. Further the method includes — to determine blood-glucose level — processing pixel signals representing the iris, separately from pixel signals representing other parts of the eye.
  • analysis of conditions in the iris is advantageous in that the iris exhibits monotonic relation- ships (peculiar to different wavelength regions) between reflected electromagnetic-radiation level and glucose concentration — enabling enjoyment of the previously mentioned benefits of measurement without spectral analysis.
  • the separation of iris and pupil signals for processing is amenable to straightforward implementation based upon geometry, leading to easy compensation for varying illumination level and the like as previously mentioned.
  • the fourth major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics.
  • the method also includes the steps of processing pixel signals representing the pupil to obtain a baseline dark level or an illumination level, or both — and also applying the dark level or illumination level, or both, to refine the pixel signals repre- senting the iris.
  • the processing step includes applying an average reflected intensity level of the pupil to represent the dark level baseline.
  • the iris-pixel signal processing comprises integrating all usable iris- pixel signals to produce a unitary intensity indication.
  • the applying step includes integrating into the indication only intensities that are higher than that of the pupil .
  • Yet another basic preference is to include the step of substantially removing image scene and illumination variation. Still another preference is to include the step of calibrating readings for an individual patient.
  • the masking step also preferably includes applying a software pupil mask that substantially stabilizes the number of iris pixels available for use, and substantially stabilizes pupil centering within the iris image. Further if this is done preferably also the pupil mask is larger than the largest pupil diameter occurring in measurement conditions.
  • said digitizing step comprises distinguishing electromagnetic-radiation-intensity changes at least as small as one part in ten thousand.
  • a finding a centroid of the pupil of the eye calculating average brightness around a pupil centroid; Q masking out the pupil region of the eye; a equalizing the iris image using the pupil brightness as a level baseline; a removing hot spots if present; a integrating all of the processed iris pixels to obtain a ni-me ⁇ cal representation of brightness level of the ris;
  • the invention is a blood-glucose measuring method for use with a small electromagnetic-radiation source. This method includes the step of automatically finding a reflection, from a patient's pupil, of the electromagnetic radiation.
  • the method also includes the step of automatically performing a position alignment based upon the location of the reflection of the electromagnetic radiation.
  • the foregoing may represent a description or definition of the fifth aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, 2 t can be seen that this facet of the invention importantly advances the art. In particular, tnis mode of operation very easily resolves several otherwise knotty problems of alignment, which can otherwise threaten the integrity of the overall measurement process — since the process is sensitive to alignment and control of signal returns from the white of the eye as well as the pupil.
  • the invention is prac- ticed in conjunction with certain additional features or characteristics.
  • the method also includes zeromg-out the area within the electromagnetic- radiation source, to form an image of forward surfaces of the eye without the electromagnetic-radiation source.
  • Another preference, especially when the method is for use with a centrally disposed electromagnetic-radiation source is the step of growing a pupil mask — starting from the electromagnetic-radiation source as a centerpoint — to cover the pupil area the image.
  • the method also includes capturing brightness level in an area under the aligned pupil mask, for use m a dark-level calibration.
  • the invention is apparatus for measuring blood-sugar concentration in a living body by measuring electromagnetic-radiation reflectivity from an eye of the body. Th s apparatus includes a detector array.
  • the apparatus also includes a small electromagnetic-radiation source held directly in front of the detector array, for directing electromagnetic radiation to the eye.
  • the apparatus has some means for receiving and measuring electromagnetic radiation reflected from the eye.
  • the apparatus also includes a lens between the detector array and the electromagnetic-radiation source .
  • the electromagnetic- radiation source shme toward the eye from substantially the geometric center of the lens — or, alternatively of the detector array.
  • the apparatus further includes some means for using a reflection of the electromagnetic- radiation source, from the eye, as a peak amplitude point for finding the image center.
  • the human being looks substantially directly toward the electromagnetic-radiation source to, substance, automatically align or center (at least approximately) the pupil the optical field.
  • the invention is apparatus for measuring blood-sugar concentration in a living body, by measuring electromagnetic-radiation reflectivity from blood of the body.
  • ⁇ he apparatus includes seme means for directing elec- tromagnetic radiation to the blood.
  • Fig. 1 is a somewhat schematic diagram, in plan, of an experimental prototype CCD camera assembly used m preferred embodiments of the invention, and contemplated for adaptation into a commercial unit;
  • Fig. 2 is a block diagram showing the image input data stream derived from optoelectronic measurements of an eye, using the Fig. 1 camera assembly a central-illummation arrangement;
  • Fig. 3 is an isometri view of a representative earlier prototype illumination geometry — one of several attempted, illustrating a d ffuse-illummation approach;
  • Fig. 4 is a like view of a prototype optical bench, particularly including a foam ocular and a forehead rest;
  • Fig. 5 is a like but more detailed view of the Fig. 4 rest;
  • Fig. 6 is a like view of an early prototype eye-track- mg system
  • Fig. 7 is a like view of an early prototype bezel for mounting at the front of the camera lens and for aiming a small electromagnetic-radiation source toward the eye;
  • Fig. 8 is an enlarged view of the Fig. 7 bezel, shown with electromagnetic-radiation source and eye, m longitudi- nal elevation generally along the system centerlme;
  • Fig. 9 is an image of part of a representative operator control panel , seen on a computer screen of our prototype apparatus while the system is imaging a subject eye;
  • Fig. 10 is a like image of another part of the same control panel display, particularly showing histograms representing results of different processing stages within the progra ;
  • Figs. 11 through 19 are a G program listing (graphical programming, as explained below) of the digital-processor code that produces output values in "arbits" (arbitrary unit ⁇ ) related to glucose concentration;
  • Fig. 22 is an image like Figs. 9 and 10, but for another display of a control panel — for a second program, used to correlate arbit values with an actual amount of patient blood sugar in conventional units;
  • Figs. 21 and 22 represent two pages of G code that represent the entire second program used to obtain calibrated IDN-to-glucose data as just mentioned;
  • Fig. 23 is a diagrammatic showing of focal-distance measurements that can be used to determine glaucoma pressure automatically with apparatus analogous to certain forms of the glucose-concentration measuring systems described here- in.
  • View A represents a normal-pressure condition
  • view 3 an abnormal or overpressure condition.
  • a method has been found to determine the amount of blood sugar without the need for invasive procedures. This technique can determine sugar levels by analyzing reflected electromagnetic-radiation information from the eye.
  • the process uses a black & white CCD TV camera and a personal computer.
  • a fully portable version that fits in the palm of one's hand is presently possible.
  • the combined result of the earnera/computer arrangement is a numeric output that displays blood-glucose levels in units of milligrams/deciliter, on a computer screen or small LCD display.
  • a handheld illumination and imaging system is used to take blood sugar measurements .
  • the system operates by integrating the reflected electromagnetic radiation from the iris portion of the eye — not from the retina. Numerous anterior blood vessels pres- ent a means of directly observing bloodstream content with exterior optical methods.
  • Glucose accumulations in this area produce a change in the intensity of reflected electromagnetic radiation.
  • the ore sugar present the higher the level of reflected electromagnetic radiation.
  • the CCD camera images the eyeball and the image is digitized. These data are processed to remove the pupil pix- els. Only the iris pixels are used as representative of glucose values as such, but as explained elsewhere the pupil pixels are used to develop baseline and illumination levels.
  • the iris pixels are integrated (summed) to produce a single intensity number.
  • IDN integer- grated data number
  • GLU glucose value
  • the IDN (or GLU) value can be calibrated by removing image scene and illumination discrepancies. It can be further calibrated to an individual patient to produce an extremely accurate IDN-to-blood-sugar correlation. Repea- table scene geometry is also very desirable for accurate measurements .
  • the primary IDN calibration technique uses pupil reflection and geometry data. Changes in input electromagnetic-radiation levels are detected by sensing pupil brightness.
  • the average reflected intensity level of the pupil is used as the dark-level baseline for IDN processing. Only intensities that are higher than that of the pupil are integrated into the IDN. This is a scene-to-scene automatic electromagnetic- radiation level calibration. If the scene electromagnetic- radiation level goes up, so do the levels of the pupil and the iris. The pupil level offsets the higher iris level and preserves the scene-to-scene relative brightness. This guarantees that only sugar-level increases will cause measured intensity increases. A further problem involves changes in pupil diameter and pupil centering within the scene. If these components are not held constant, the total number of iris pixels available for integration will change.
  • a software pupil mask is em- ployed. This zeroes-out a fixed region around the pupil.
  • Some iris pixels are zeroed the process, but all image frames are treated the same way.
  • the pupil mask is always the same size, and therefore all image frames contain the same number of iris pixels. The geometric distortions due to pupil variations are eliminated.
  • Another source of error is produced from illumination hot spots. Good electromagnetic-radiation source diffusion is needed to prevent the problem.
  • Hot-spot removal can be partially accommodated with software. Peak signal amplitudes are removed before the integration process. In addition, Hot Spot mapping can be used to extract the troublesome regions prior to integration.
  • Image contrast equalization (stretch) is also applied. Th s causes pixels to fill the complete dynamic range of pixel data words .
  • the pupil baseline data is applied to this process, permitting only the pixels that are brighter than the pupil to be remapped. As a result, further processing takes place using data that have been scene-level-biased and equalized to ⁇ . full amplitude range. 3. CALIBRATION AND READOUT
  • the process of converting the IDN to a true glucose measurement requires a simple lookup operation to verify that the result is within a predetermined error band.
  • the correlation from IDN to milligrams per deciliter (mg/dL) can be seen in the following formula.
  • IDN.,,-,,. - IDN ⁇ IGN • GL + IDN.- ⁇ .
  • IDN-- ⁇ highest possible IDN (integrated data number)
  • G aa -. highest possible glucose value ( mg/dL)
  • GL ⁇ n lowest possible glucose value (mg/dL)
  • Inserting a milligram/deciliter value m GL yields its equivalent IDN value in IGN. Going from IDN to GL is accomplished by searching or hashing a lookup table. When the IDN value is equal or almost equal to a bounded IDN table value, GL is retrieved from the table and output as the glucose reading.
  • the IDN lookup table is produced by averaging multiple calibrated IDN samples for known glucose values.
  • a fixed error range s based on a plus-or-mmus deviation percentage from the average IDN .
  • H search a lookup table to find the closest IDN-to-GL match
  • the electromagnetic-radiation source becomes a peak amplitude point for finding the image center.
  • the software finds the electromagnetic radiation (seen as a hot spot m the center of the pupil) and performs a position alignment based on its location.
  • the software Having found the center of the pupil, the software also performs the following processes.
  • H grow a pupil mask from the electromagnetic-radiation- sourca centerpomt and use it to cover the pupil area the image
  • a reverse signal response takes place with near infrared illumination.
  • the infrared reverse effect can be used to improve system accuracy.
  • Infrared illumination yields a nonlinear con- version that produces a large dynamic range in the low-sugar region. This information can be processed for enhanced low- end performance .
  • a combination of visible and infrared processing can be done to produce dual response tables. These "inverse" re- sponse tables can be correlated to automatically verify the validity of glucose measurements. This technique produces additional accuracy and means of system self-calibration.
  • a high-resolution black-and-white digital video camera assembly uses a charge-coupled detector (CCD) array- as a sensor.
  • the camera includes a body 10 for housing the CCD array, a mounting section 11 with an attachment thread 29, a camera bias-voltage connector 12, and a video-out connector 13.
  • An extension tube 14 holds a 1:1.4 lens 15, making the focal length approximately 2 . cm (one inch) .
  • the purpose of the extension tube is to maximize the amount of data from the iris 32 (Fig. 2) of the eye 30 and limit, to zero, the amount cf white of the eye
  • a Snappy manufactured by Play Inc. , is an lmage- capture card for a personal computer (PC) . It captures a one-thirtieth-second frame from a moving image and stores it for future analysis.
  • the frames used are advantageously similar; the total digital numbers are preferably as close to each other as possible.
  • a small electromagnetic-radiation source 33 (Fig. 2) directs electromag- netic radiation 34 toward the center of an eye 30, and reflections 35 from the pupil 31 and iris 32 traverse the lens 15 to the CCD camera 10. Note that no optical dispersing or wavelength-selecting device s included.
  • the CCD camera 10 sees the reflected electromag- netic radiation 35 from the eye.
  • Raw video data 37 go to a digital interface 38, which responds with corresponding digital data 39 that proceed into a computer 40.
  • Figs. 1 and 2 The central-illumination arrangement of Figs. 1 and 2 was the successor to numerous earlier efforts based instead on diffuse illumination of and data collection from the eye.
  • electromagnetic radiation from a forty-watt incandescent party bulb 43 was integrated by flat white paint on the walls of the room itself — essentially a large mtegratmg-sphere concept.
  • the electromagnetic-radiation was arranged to approach the eye 30 at a right angle to the optical axis 41 between the lens ana the eye, to minimize formation of reflections and shadows.
  • the illumination was passed through a diffuser 42 — created from a plain white paper cylinder placed around the electromagnetic-radiation source.
  • a diffuser 42 created from a plain white paper cylinder placed around the electromagnetic-radiation source.
  • an optical bench with a foam ocular 45 (Fig. 4) was built.
  • a headrest (Fig. 5) helps stabilize the eye .
  • the optical bench three feet long, was fashioned from two aluminum rails 47 (Fig. 4) — a rectangular one, lying horizontal, and a square bar turned on the diagonal so that one corner fits into corresponding notched grooves in the base 48 of the headrest and in the base of the camera support.
  • the bar allows movement only along the z-axis (i . e. , longitudinally) .
  • This geometry also allows setting of distances between the headrest (i . e. , the eye position) and the camera .
  • the support stand allows up-and-down (y-axis) adjustment by means of a vertical red with an adjustment knob.
  • the two rails are kept parallel by being mounted on two eight-inch crossbars with three legs made from machinist jackscrew ⁇ . One leg is attached to the center of the cross- bar; the other two legs are attached at opposite ends of the other crossbar, thereby allowing leveling in a classical manner .
  • the headrest is mounted to a sliding aluminum base 48, to support two one-foot-long threaded vertical rods 54 hold- ing a curved aluminum forehead piece 46.
  • the whole mechanism is mounted on a centered vertical support rod 53.
  • a crossbar 52 supports a subject' s chin on a soft pad (not shown) , and the forehead rests against the forehead piece 46 to stabilize the head. Adjustment and locking are facili- tated by an adjustment screw 52.
  • the CCD camera is also mounted on a support rod, set in a commercial support stand.
  • the rod is attached to the camera, which is inside a tubular cardboard electromagnetic- radiation shield 49 (made from a cardboard mailing tube) .
  • a trapdoor allows for adjustments to the camera with two camera-support screws through the tubular shield, centering the camera in the shield.
  • the tube is four inches in diameter and fourteen inches long.
  • the trapdoor is eight inches long and sections out half of the tube, starting one inch back from the front.
  • the camera lens face is flush with the end of the tube.
  • the interior of the tube is painted flat white.
  • a pair of slip-tube swing arms 69 (Fig. 6) fixed to the camera mounts — above and below the tubular shield 49 — held a vertical rod 61 on which a block 62 slides up and down 64 , carrying a electromagnetic-radiation-emitting diode (LED) 63.
  • the LED served as the electromagnetic-radiation source for central illumination.
  • the slip tubes enabled horizontal adjustments 66, and the LED block vertical movement 64.
  • a video monitor is used to show real-time video of the eye being viewed for data collection.
  • the subject views his or her own eye on the monitor, and can rapidly correct for positioning of the eye, thus minimizing the amount of white cf the eye showing — and allowing for detection of unwanted reflections. Looking at a real-time video is faster and easier than doing eye-track- mg using the mechanical tracking system.
  • Selected single frames were stored using a frame grabber or Snappy 01 image-capture card.
  • data collection took a long time because frames with high data error — usually half of the frames taken — had to be dis- carde .
  • Bezels were made to accommodate two sizes of LED: a so-called “Tl” 3mm and a “T-1V (5 mm) .
  • the larger LED masks th ⁇ - entire pupil — thereby negating the data that o would be gathered for pupil calibration.
  • the data collected is nevertheless very useful in obtaining the correction factor to establish total system linearity.
  • the bezel portion that goes over the lens shade has a 1.39 inch inside diameter, with a 0.05 inch wall, 0.3 inch 5 deep.
  • the web that holds the LED has a thickness of 0.04 inch (to minimize the masking of data from the iris to the CCD camera) and is 0.125 inch deep.
  • a goal during data-taking is to illuminate the iris to the point, at least, 1/2 full well on the total digital number (D/N) possible — or alternatively full well of the CCD camera.
  • Empirical data-collection and -manipulation sug- gests that 1/4 full well may be a minimum needed to provide the amount of data necessary for all manipulation of calibration, subtraction and averaging for our experimental prototype system.
  • our invention contemplates — as a first step toward portability — making a hybrid integrated circuit to replace the PC. It also appears worthwhile to develop a "foolproof" transmitter coded to transmit blood-sugar values directly to a diabetic' s insulin pump, as well as calculation of utilization time and amount of insulin. Eventually continuous readings through a convenient means — such as for example eyeglass-mounted sensors — would bring the diabetic and others back to a more-normal life.
  • a so-called "graphical programming language” accepts program commands, including flow of logic, not as verbal syntax but rather in the form of geometrical connections and relationships among diagrammatic elements as in Figs. 11 through IS.
  • Such graphical entries are interpreted by a compiler analogously to the way m which verbal syntax is interpreted in use of more-traditional programming languages .
  • Glucon has several experimental features (filters, pixel comparison algorithms, adjustable display mode, etc.). It evolved during early experimentation phases to permit t ⁇ al-and-error analysis of the image data. In the state described here, it is used to process eye image input and automatically yield the final glucose measurement as described above. While our system is imaging a subject eye, them computer screen displays an operator control panel (Fig. 9) that includes various buttons and other controls — and also both the image presentation (at left) and the GLU or IDN values in milligrams per deciliter (mg/dL) as calculated from the images. In addition, histograms show (Fig. 10) the results of different processing stages within the program.
  • the G program produces the results described above.
  • the first program, Glucon (listed in Figs. 11 through 19), is the software key to extracting information in accordance with this invention. It embodies all necessary algorithms and techniques for primary operation of the invention to obtain IDN or GLU values.
  • the second program, Average is used to correlate the IDN or GLU values obtained from an imaged eye with the actu- al amount of patient blood sugar. It processes a user-selectable number of images of a subject eye, all taken at a particular sugar level — i . . in quick succession.
  • Average creates a statistical box and then obtains the average and absolute IDN or GLU limits. These values are used to build a table of IDN-to-blood-sugar conversions .
  • Fig. 20 shows the on-screen operator control panel of Average.
  • Figs. 21 and 22 represent three pages of G code that represent the entire program, Average, used to obtain calibrated IDN-to-glucose data from the IDN or GLU values. 9 .
  • GLAUCOMA MEASUREMENTS
  • the distance F ⁇ r ⁇ s ID (Fig. 23) represents the distance from the vertex plane of a CCD camera lens 15 to the
  • the incremental distance 91 which is to say the difference F- . -.- . ,. 1 ⁇ - F ⁇ r ⁇ s 0D (or ratio) between the two distances,
  • Focal determinations thus yield a measure of intraocular pressure, a large distance corresponding to high pressure and a small distance to low pressure.
  • Depth of field for example 0.3 mm (0.012 inch), may form a limitation on this technique.

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  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Optics & Photonics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Emergency Medicine (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Image Processing (AREA)
  • Image Analysis (AREA)
  • Eye Examination Apparatus (AREA)

Abstract

La réflectivité d'un rayonnement électromagnétique émanant du corps est mesurée. Un procédé de l'invention permet de mesurer, sensiblement sans analyse spectrale. L'oeil (30) est un organe du corps qui se prête particulièrement à cette mesure. Une mosaïque de détecteurs monochrome des camérasCD monochromes (10), par exemple suffit pour effectuer ces mesures. L'appareil détecte des changements de niveau du rayonnement réfléchi et rapporte ces changements à la concentration de glucose. La relation est monotone quant au rapport de la glucose à la grandeur du rayonnement réfléchi. Le système peut fonctionner à la lumière visible, notamment dans le jaune et/ou le jaune-vert, et peut prendre en compte une réponse du signal de retour dans le rouge et/ou l'infrarouge.
PCT/US1999/021680 1998-09-18 1999-09-17 Mesure non invasive de la glycemie fondee sur des observations optoelectroniques de l'oeil WO2000016692A1 (fr)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU61536/99A AU6153699A (en) 1998-09-18 1999-09-17 Noninvasive measurement of blood sugar based on optoelectronic observations of the eye
CA002390520A CA2390520A1 (fr) 1999-09-17 2000-01-21 Mesure non invasive du niveau de sucre dans le sang
JP2001525185A JP2003524153A (ja) 1999-09-17 2000-01-21 血糖レベルの非侵入的測定
KR1020027003472A KR20020070964A (ko) 1999-09-17 2000-01-21 혈당 수준의 비 관혈적 측정법
EP00909963A EP1216409A1 (fr) 1999-09-17 2000-01-21 Mesure non invasive du niveau de sucre dans le sang
PCT/US2000/001698 WO2001022061A1 (fr) 1999-09-17 2000-01-21 Mesure non invasive du niveau de sucre dans le sang
AU32135/00A AU3213500A (en) 1999-09-17 2000-01-21 Noninvasive measurement of blood sugar level
US09/489,593 US6853854B1 (en) 1998-09-18 2000-01-21 Noninvasive measurement system
US10/783,671 US20050171416A1 (en) 1999-09-17 2004-02-20 Noninvasive measurement system
US11/552,100 US7869848B2 (en) 1999-09-17 2006-10-23 Noninvasive measurement system
JP2010189230A JP2010284552A (ja) 1998-09-18 2010-08-26 血糖レベルの非侵入的測定
JP2010189026A JP2010276616A (ja) 1998-09-18 2010-08-26 血糖レベルの非侵入的測定

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10080498P 1998-09-18 1998-09-18
US60/100,804 1998-09-18

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/489,593 Continuation US6853854B1 (en) 1998-09-18 2000-01-21 Noninvasive measurement system

Publications (2)

Publication Number Publication Date
WO2000016692A1 true WO2000016692A1 (fr) 2000-03-30
WO2000016692A9 WO2000016692A9 (fr) 2000-07-13

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/021680 WO2000016692A1 (fr) 1998-09-18 1999-09-17 Mesure non invasive de la glycemie fondee sur des observations optoelectroniques de l'oeil

Country Status (3)

Country Link
JP (2) JP2010284552A (fr)
AU (1) AU6153699A (fr)
WO (1) WO2000016692A1 (fr)

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WO2001022061A1 (fr) * 1999-09-17 2001-03-29 Proniewicz Walter K Mesure non invasive du niveau de sucre dans le sang
US6853854B1 (en) 1998-09-18 2005-02-08 Q Step Technologies, Llc Noninvasive measurement system
US8090424B2 (en) 2005-01-10 2012-01-03 Sti Medical Systems, Llc Method and apparatus for glucose level detection
US9442065B2 (en) 2014-09-29 2016-09-13 Zyomed Corp. Systems and methods for synthesis of zyotons for use in collision computing for noninvasive blood glucose and other measurements
US9554738B1 (en) 2016-03-30 2017-01-31 Zyomed Corp. Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing

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Publication number Priority date Publication date Assignee Title
CN110376168A (zh) * 2019-06-18 2019-10-25 江西掌护医疗科技有限公司 远程血糖检测系统

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US5553617A (en) * 1995-01-20 1996-09-10 Hughes Aircraft Company Noninvasive method and apparatus for determining body chemistry
JP3604231B2 (ja) * 1996-05-16 2004-12-22 富士写真フイルム株式会社 グルコース濃度測定方法および装置
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US5569186A (en) * 1994-04-25 1996-10-29 Minimed Inc. Closed loop infusion pump system with removable glucose sensor

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6853854B1 (en) 1998-09-18 2005-02-08 Q Step Technologies, Llc Noninvasive measurement system
WO2001022061A1 (fr) * 1999-09-17 2001-03-29 Proniewicz Walter K Mesure non invasive du niveau de sucre dans le sang
US8090424B2 (en) 2005-01-10 2012-01-03 Sti Medical Systems, Llc Method and apparatus for glucose level detection
US9442065B2 (en) 2014-09-29 2016-09-13 Zyomed Corp. Systems and methods for synthesis of zyotons for use in collision computing for noninvasive blood glucose and other measurements
US9448165B2 (en) 2014-09-29 2016-09-20 Zyomed Corp. Systems and methods for control of illumination or radiation collection for blood glucose and other analyte detection and measurement using collision computing
US9448164B2 (en) 2014-09-29 2016-09-20 Zyomed Corp. Systems and methods for noninvasive blood glucose and other analyte detection and measurement using collision computing
US9453794B2 (en) 2014-09-29 2016-09-27 Zyomed Corp. Systems and methods for blood glucose and other analyte detection and measurement using collision computing
US9459201B2 (en) 2014-09-29 2016-10-04 Zyomed Corp. Systems and methods for noninvasive blood glucose and other analyte detection and measurement using collision computing
US9459202B2 (en) 2014-09-29 2016-10-04 Zyomed Corp. Systems and methods for collision computing for detection and noninvasive measurement of blood glucose and other substances and events
US9459203B2 (en) 2014-09-29 2016-10-04 Zyomed, Corp. Systems and methods for generating and using projector curve sets for universal calibration for noninvasive blood glucose and other measurements
US9610018B2 (en) 2014-09-29 2017-04-04 Zyomed Corp. Systems and methods for measurement of heart rate and other heart-related characteristics from photoplethysmographic (PPG) signals using collision computing
US9554738B1 (en) 2016-03-30 2017-01-31 Zyomed Corp. Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing

Also Published As

Publication number Publication date
JP2010284552A (ja) 2010-12-24
WO2000016692A9 (fr) 2000-07-13
AU6153699A (en) 2000-04-10
JP2010276616A (ja) 2010-12-09

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