EP0274521A1 - Testverfahren -i(in vivo) für erythrozytenindices - Google Patents
Testverfahren -i(in vivo) für erythrozytenindicesInfo
- Publication number
- EP0274521A1 EP0274521A1 EP87905049A EP87905049A EP0274521A1 EP 0274521 A1 EP0274521 A1 EP 0274521A1 EP 87905049 A EP87905049 A EP 87905049A EP 87905049 A EP87905049 A EP 87905049A EP 0274521 A1 EP0274521 A1 EP 0274521A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- red blood
- images
- image
- blood cells
- analysis
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
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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
- A61B5/14551—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 for measuring blood gases
- A61B5/14555—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 for measuring blood gases specially adapted for the eye fundus
-
- 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
- A61B5/14535—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 haematocrit
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
- A61B5/411—Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
- G01N2015/012—Red blood cells
Definitions
- the present invention relates to the measurement of blood cell indices and, more particularly, to apparatus and methods for in vivo quantitative measurement of red blood cell indices.
- red blood cell count and the determination of red blood cell indices are the most frequent of all clinical laboratory tests performed on patients in doctors' offices, clinics and hospitals in the United States and throughout the world. These tests provide essential information as to health characteristics of individuals of all age groups.
- Processes for evaluating and testing blood which are in widespread use in the art today uniformly require a sample of blood to be removed from the body for testing and analysis.
- the procedure for taking blood known as phlebotomy, ordinarily involves the removal of blood from capillary or peripheral blood (usually in infants) and venous blood. Only certain licensed persons are permitted by law to carry out this procedure. These include nurses, laboratory technicians, physicians, and other specially trained persons.
- the sample is ordinarily from the palmar surfaces of the tip of a finger or the planar surfaces of the great toe or heel.
- the site is first rubbed vigorously with a gauze pad moistened with seventy-percent alcohol to remove dirt and debris and to increase blood circulation.
- a puncture 2-3mm deep is made with a blade or lancet.
- slight pressure is applied to the area of the puncture with a gauze pad. This procedure is usually painful and frightening to the infant which results in further difficulties in e££ssct ⁇ ng the phlebotomy.
- the most common form of adult patient phlebotomy involves the removal of venous blood through puncture of a vein in the patient's arm. This procedure is also somewhat painful and is viewed with apprehension by most patients. Veins must be carefully inspected, particularly with those patients who have already had numerous punctures. The patient's life may depend on vein patency, and care mast be taken to preserve these vessels. Hematomas or ecchymoses are usually evidence of the operator's poor technique or judgment. The equipment necessary for this procedure ordinarily includes a syringe and a needle of the appropriate diameter. This needle must be carefully inspected as a blunt or bent tip will damage the patient's vein and often lead to failure to collect blood from the vein. A tourniquet is also used in the procedure in order to make the veins more prominent and help to eliminate blind probing.
- the procedure involves making the patient comfortable, preferably having them sit in a chair with the patient's arm accessible to the operator.
- the tourniquet is then applied and the skin surrounding the target site is cleaned with a seventy-percent alcohol solution and permitted to dry.
- the needle is pushed into the vein with a single direct puncture of both the skin and the vein.
- the tourniquet is then loosened and the desired amount of blood is obtained.
- the operator must be aware of the patent at all times as the trauma of venipuncture can cause the patient to faint. After the procedure is complete operator must also insure that the patient's condition satisfactory before he is dismissed.
- Complications of venipunctures do occur and include a measurable increase in the concentration of blood cells when the tourniquet is applied for periods greater than sixty seconds. Failure of the blood to enter the syringe may also occur. This may result from excessive pull on the plunger of the syringe which can cause the vein to collapse. The piercing of the outer coat of the vein without entering the lumen can also account for failure. These complications are occasionally followed by hematoma formation. When this occurs, the needle must be withdrawn and the procedure must be carried out on the other arm. Late complications include possible thrombosis of the vein due to trauma, especially following many venipunctures at the same site. Finally, where non-disposable or contaminated needles are used, the transmission of contagious diseases such as serum hepatitis, etc. may be effected.
- Hct hematocrit
- Hb hemoglobin
- the Hct of a sample of blood is defined as the ratio of the volume of erythrocytes (red blood cells) to that of the whole blood» It is expressed as a percentage or, preferably, as a decimal fraction.
- the units (L/L) are implied.
- the venous hematocrit agrees closely with the hematocrit obtained from a skin puncture; both are greater than the total body hematocrit.
- Hemoglobin the main component of the red blood cell, is a conjugated protein that serves as a vehicle for the transportation of oxygen and CO 2 , throughout the body. When fully saturated, each gram of hemoglobin holds 1.34 ml of oxygen.
- the red cell mass of the adult contains approximately 600g of hemoglobin, capable of carrying 800 ml of oxygen.
- the main function of hemoglobin is to transport oxygen from the lungs, where oxygen tension is high, to the tissues, where it is low.
- hemoglobin (Hb) refers to the concentration of the iron-containing protein pigment found in red blood cells.
- the Hct and Hb are often provided along with the total red blood cell count (RBC) which is usually expressed in the.form of a concentration — cells per unit volume of blood.
- RBC red blood cell count
- MCV mean cell volume
- MCV Hct x 1,000/RBC (in millions per u)
- the mean cell hemoglobin (MCH) may also be calculated and is the content of Hb in the average red blood cell; it is calculated from the Hb concentration and the RBC utilizing the following formula:
- This index is the average concentration of Hb in a given volume of packed red blood cells. It is calculated using the following formula:
- red blood cells which are available utilizing today's testing methods include values for the variability of the MCV about a mean value and estimates of abnormality in red blood cell morphology.
- Hct the ratio of packed red blood cells to volume of whole blood
- the volume is then calculated by measuring the level of the red blood cells as a ratio of the total volume.
- Sources of error in this method include insuring that the sample is subject to adequate centrifugal force for a sufficient duration so that the red cells may be packed and give an accurate reading. In addition, the final value must be corrected for trapped plasma present within the packed red blood cells.
- Technical errors in this method include failing to mix the blood adequately before sampling, improper reading of the level of cells to plasma, and irregularity of the inside diameter of the specimen tubes.
- Methods used in the art to determine the Hb in a sample of blood include the cyanmethemoglobin method, the oxyhemoglobin method and the method of measuring iron content of the sample. Of the above three methods, the first (the cyanmethemoglobin method) is recommended by the International Committee for Standardization in Hematology.
- That method involves diluting a sample of blood in a solution of potassium ferricyanide and potassium cyanide.
- the potassium ferricyanide oxidizes hemoglobins and potassium cyanide provides cyanide ions to form hemiglobincyanide which has a broad absorption maximum at a wavelength of approximately 540nm.
- the absorbence of the overall solution can then be measured in a photometer or spectrophotometer at 540nm and compared with that of a standard hemiglobincyanide solution.
- the oxyhemoglobin method is not widely used, however it does yield reproducible results.
- the main disadvantage however is the lack of a stable standard with which to compare the results.
- This method involves the creation of a 1:251 dilution of blood in 0.007 N NH4OH utilizing distilled water. This solution is then shaken to insure proper mixing and oxygenation of the hemoglobin. The solution is read in a photometer with a green filter with a .007 N ammonium- hydroxide solution used as a standard.
- the last method listed above involves a procedure whereby Hb may be measured by determining the iron content of the whole blood.
- the non-hemoglobin iron in blood is negligible compared to hemoglobin iron, however, the iron ' must first be separated from the hemoglobin, usually by acid or by ashing. It is then either titrated with iCl ⁇ or compjl ' exBd with a reagent to develop color that can be measured photometrically since the iron content of hemoglobin is given as 0.347 percent, the concentration of hemoglobin in blood is calculated by dividing the iron concentration by 3.47.
- Errors inherent in the sample include .improper venipuncture technique which may introduce hemo concentration, which will make hemoglobin concentration and cell counts too high.
- the photometer used for determining Hb must be calibrated in the laboratory before its initial use and must be re-checked frequently.
- the wavelength settings, filters and meter readings require constant monitoring.
- the RBC, or red blood cell count may be determined by a number of different cell counting procedures. Any of these procedures includes three steps: dilution of the blood, sampling the diluted suspension into a measured volume, and counting the cells in that volume, and counting the cells in that volume.
- Optical and electronic equipment have been developed to perform red blood cell counting, inter alia, in flowing systems in vitro. This equipment can also separately measure Hb by a chemical method in a separate analytic channel. The most widely used of such instruments is manufactured by Coulter Diagnostics of Hialeah, Florida, wherein red blood cells are passed through a glass tube with an aperture such that single cells can be detected based on a decrease in the voltage between electrodes positioned in a constricted portion of the tube.
- Image analysis has been utilized to examine stained smears of blood fixed to glass slides with computer-controlled microscopes.
- Examples of such instruments include the "Hematrak” instruments manufactured by the Geometric Data Corp., Wayne, PA. These instruments utilize pattern recognition software which identifies each of the major classes of white blood cells according to size, shape, staining and other morphologic characteristics. They also identify red blood cells for their morphology.
- the imaging system includes a microscope with an automated scanning stage and an automatic focusing objective. Filters split the light transmitted through the stained into red, blue, and green portions of the spectrum. These allow the staining properties of the portions of the cells to be characterized. These instruments, however, do not produce any quantitative measures of red blood cells. These, and similar instruments, are also characterized by their in-vitro analysis of stained blood, fixed to slides for analysis. None perform quantitative analysis of red blood cell parameters.
- IRIS International Remote Imaging Systems
- This system utilizes a flow analyzer and system described in U.S. Patent No. 4,338,024, issued to Bolz, et al., and assigned to IRIS.
- urine specimens are aspirated through a flow cell which is designed to orient cells and particles in one plane. Moving particles and cells are then photographed by a high-speed camera and counted by a microprocessor programmed to identify and classify the different particles and cells, including red blood cells. No quantitative analysis of red blood cell parameters is performed and the spectral analysis utilized is by transmission, rather than reflectance spectrophotometry.
- a video computer system for measuring the lineal density of red blood cells and capillaries in vivo is described in an article by C. G. Ellis, et al. in Microvascular Research 27, Pages 1-13 (1984) .
- This system utilizes a computerized frame-by-frame analysis of video images in order to perform continuous measurements of lineal density based on the spatial-average of blood capacity over a selected length of capillary.
- This method does not attempt to measure or even detect individual RBCs, but rather is directed to the measurement of light intensities along the centerline of the image of a capillary such that the number of RBCs in a given length of capillary is inversely related to the average light intensity over that length.
- a light intensity profile is determined utilizing a video analyzer which, for each frame, measured the light intensity values along a given length of capillary, first in the absence of RBCs to determine the "background light intensities" and then as the flow of RBCs is reestablished.
- a plot of mean opacity versus RBC for a particular capillary segment is then plotted and thus a value for RBC is estimated given a particular measured mean opacity. This system does not measure Hb, Hct or any of the other indices directly.
- a variant of a conventional ophthalmoscope is used to visualize and capture images of red blood cells in capillaries, small arteries or veins of the mucus membranes which line the inner surface of the eyelids and the exposed surface of the eye outside the iris (known as the conjunctiva) , retina or other accessible sites on the mucus membranes.
- capillaries are present whose visible appearance under magnification shows a continuous stream of blood.
- the opthalmoscope is used to identify and capture images of this blood flow in capillaries which are sized to allow the flow of only one or a few blood cells at a time to pass a given point.
- the computerized image analysis system directly measures characteristics of red blood cells including the boundaries of the individual red blood cell and, utilizing algorithms which relate area to volume, directly computes the volume of that particular cell. This measurement and calculation is carried out on a large number of red blood cell images captured by the opthalmoscope which, when averaged, yield a direct measured value for mean cell volume (MCV) without the need for establishing or estimating the hematocrit (Hct) or red blood cell number (RBC) .
- MCV mean cell volume
- Hct hematocrit
- RBC red blood cell number
- the mean cell hemoglobin concentration is determined simultaneously with the direct measurement of MCV by measuring the intensity of red color (from the iron-containing protein pigment) which is attributable to that pigment. That intensity relates to a given concentration of hemoglobin within the cell.
- This measurement of intensity can be done either by incorporating a spectroscopic photodetector which selects and measures the wavelength peak maxima characteristics of hemoglobin or by incorporating a filter in an optical chopper that absorbs the wavelengths characteristic of hemoglobin to yield a value by subtraction spectral analysis.
- the volume of the captured red cell undergoing image analysis is known from given algorithms relating area to volume and the intensity is measured as indicated above. Together they yield a hemoglobin concentration for that particular red blood cell.
- MCHC mean cell hemoglobin concentration
- the Hb and RBC can be easily calculated. While a relative value for the Hct can be measured, that measurement will not represent the central hematocrit as yielded by in vitro instrumentation in use in the art today. This difference stems from the fact that the present apparatus measures the Hct within the capillary itself as a proportion of the space within the still image occupied by red blood cells as opposed to the space which is not occupied by red blood cells.
- the central Hct represents the ratio of the volume of red blood cells to that of the whole blood as taken from a specimen removed from a vein of the patient and subject to centrifugation.
- FIG. 1 is a schematic block diagram of an apparatus in accordance with one embodiment of the present invention.
- FIG. 2 is a schematic block diagram of video analysis components of one embodiment of the present invention.
- FIG. 1 shows a schematic block diagram of one preferred embodiment including a focusable light source and visual image receiver 20 for capturing images of the red blood cells in conjunctival capillaries of the eye 22.
- This focusable light source and visual image receiver (FLS-VIR) is preferably a conventional ophthalmoscope or slit lamp similar to those manufactured by Welch-Allyn of Skaneateles Falls, New York, or Zeiss Co. Either of these conventional FLS-VIR devices can be equipped with additional magnification capability to make them adaptable for use with the present invention. Since red blood cells average 7.4 microns in diameter and have an average volume of 87 +5 cubic microns, some magnification is necessary for accurate analysis. This magnification falls within the range of from 150X to about 65OX depending upon the analysis equipment used.
- conjunctiva Sufficient light must be available to permit ordinary visualization of the small blood vessels of the conjunctiva, including the capillaries, arterioles and venules.
- the conjunctiva will be referred to herein in further descriptions however it is important to note that other sites can also provide satisfactory images of red cells _in vivo according to the present invention.
- the conjunctival capillaries are preferred because they are readily accessible and provide an excellent contrast between the red blood cells in the capillaries and the white background of the conjunctiva. .
- the FLS-VIR 20 is adapted to allow for subsequent image splitting, and transmission to an optical enlarger 24 for enlargement and processing. Transmission of these images is preferably through fiber optic transmission lines, however, any appropriate transmission medium is acceptable.
- Subsequent processing and transmission of the images captured and magnified by the FLS-VIR can include for example slit lamp cameras and/or video camera attachments similar to those used for operating room ophthalmoscopes, micro-surgical devices and television opthalmoscopy.
- the elements of the FLS-VIR can be mounted in a rigid assembly wherein the patient's head is maintained in a fixed cradle similar to current slit lamp fixtures.
- the image can be viewed directly by the physician and also split to a side viewing port for subsequent computerized image analysis.
- the image splitter discussed above diverts a portion of the image visualized by the operator and subjects that image to further analysis.
- the image splitting can be accomplished by several well-known techniques utilizing various optical devices. These devices include partially reflective mirrors and interspersed fiber optical strands.
- Instrumentation for this subsequent analysis includes an image magnifier 24, a light chopper and filter 26 and a video camera scanner or projector 28.
- the images produced directly on the pickup tube of an ordinary vidicon-type television camera would be approximately 9.4 x 12.5 mm and require approximately 1.0 foot candles. This image can be displayed on a printer/screen 31 either prior or subsequent to analysis by computer 30.
- the split image of the red blood cells can be passed through the beam splitter enlarging optics 26 and filtered either before or after being transmitted by fiber optics transmission lines to a television pick-up tube.
- Video signals of sufficient quality for image analysis are produced by silicon diode vidicons that have a 5-10X sensitivity of standard vidicons, with light levels of 0.1 to 0.2 foot candles at the base plate of the tube.
- a phosphor screen-fiber optic device may be employed, such as is used to obtain images from transmission electron-microscopy (TEM) , with a sensitive TV screen also equipped with fiber optics.
- Weak signals may be enhanced through electronic amplification and/or computer processing of the signals that reach the vidicon so that accurate image analysis can be performed.
- the captured image is presented to a video camera which subsequently transforms the image into electronic information to be subsequently analyzed by 30.
- Hb analysis is performed by interposing an optical chopper 24 inline with the image transmission.
- the chopper consists of a conventional motor driven wheel having a filter slot with an appropriate filter. That filter is designed to absorb the specific energy in the red portion of the spectrum corresponding to the maxima of absorption of the hemoglobin of red blood cells. This maxima is generally in the range of about 650nm.
- the filter should have a broad absorption band width on either side of the maxima in order to remove the light characteristic of hemoglobin from the subsequent image and image processing. This light characteristic results during the very short instant when the rotating wheel interposes the filter between the primary image of the red cell that has been illuminated with white light and a subsequent image or transformed data representing the earlier image.
- the instantaneous image of each red blood cell analyzed by the instrument will be presented both with and without the intensity of red light that is entirely attributable to the iron-containing protein pigment of hemoglobin.
- the hemoglobin concentration of each red blood cell will then be determined by subtraction of the signal generated by the pigment from the background in the same cell and calculated according to Beers' Law as modified by the characteristics that change in the case of reflectance vs transmission spectroscopy and may be confirmed empirically. Utilizing this technique, a computer receiving this data performs subtraction reflectance spectrometry to determine the hemoglobin concentration of each individual red blood cell analyzed.
- the Optical Image Receiver Enhancer-Enlarger functions to receive, encode, and, in one version, to enlarge the image and make it suitable for visual analysis and display by other components of the instrument.
- the receiving component of the OIREE is, in one embodiment, a high speed video camera with a very rapid shutter sufficient to allow the capture of instantaneous images of red blood cells.
- the shutter speed should be slow enough to allow the optical chopper described above to provide an image with and without red filtering, and yet fast enough to preserve discrete cell margins without blurring.
- Ordinary vidicons, silicon diode vidicons with high sensitivity or such vidicons as the "15-3 precision scanner" used by Bausch & Lomb in the Omnicon 5000, can be employed.
- vidicons may be combined advantageously with software to accommodate and correct for non-uniform distributions of light falling on the vidicon so as to make the signals readily analyzable by the image analysis components of the apparatus.
- Optical enhancement can be achieved by several established techniques. The primary function of this component is enlargement.
- the unenhanced image can be enlarged through conventional optics by means of a series of lenses as in a telescope or microscope.
- the image that has been received directly into a video camera can be enlarged by the action of the video camera.
- This enlarged image is then operated upon by image enhancement programs to detect, clarify and sharpen boundaries between red blood cells and their surroundings, and to enhance color characteristics.
- This component may, alternatively, be positioned in line before, after, or among several others of the instruments depending upon the preferred configuration.
- the enlarged image from the OIREE is preferably projected on to a video screen.
- the raster of this screen can provide subsequent enlargement and enhancement functions where the OIREE has not yet operated upon the enlarged image of the red blood cell and is essentially functioning only as a video camera projection.
- the video camera can record the continuously generated captured images on to a recording medium such as video tape, which can then be played into the video projector at varying speeds and used to obtain images for subsequent analysis by Computer 30.
- a recording medium such as video tape
- a series of light images 34 of flowing red blood cells are produced on the photo sensitive face of a special vidicon camera tube 36 by an optical system which includes an image splitter, a light chopper-filter, enlarging optics and a signal amplifier.
- the brightness forming the image at each point on the screen is converted into electrical voltages by repeatedly scanning the image with an exploring spot formed by the electron beam of the camera tube. This spot formed by the electron beam of the camera tube. This spot generates an electrical video signal which indicates the brightness at each of its instantaneous positions.
- the video signal 38 is amplified in a conventional video amplifier 40 and may, optionally, be combined with a video display (not shown) .
- That signal determines the brightness of a reproducing spot formed by the display tubes' electron beam.
- the reproducing spot moves over the latter screen synchronously and is coordinated with the exploring spot.
- the reproducing spot reconstructs the brightness distribution of the image that was received on the vidicon camera face with the possibility of enlargement and/or amplification of signal intensity.
- the amplified video signal 41 is then subject to correction for "shading" and sensitivity adjustment.
- the corrected amplified video signal 44 is then encoded 46 for subsequent translation into critical information. Conversion of the signal to digital values is accomplished by a high resolution digitizer 48 and oxrcurs in real time. These values are transmitted to a, computer through a data base and memory register. Th video signal that actually produces the video display is generated from this memory.
- the system may also be provided with a separate input means 54 such as a keyboard so that patient and specimen information can be included in the display and analysis.
- Computer 30 performs analyses the data representing the images of red blood cells developed by the previously described components. From this data, the red blood cell analyses and indices are produced.
- the functions carried out by the computer include image analysis to determine the size of each red blood cell analyzed. Image processing programs will select only those red blood cells which conform to pre-selected criteria. That criteria insures uniform orientation of the cells so that they are imaged with their maximal surface perpendicular to the optical path. Since red blood cells circulate as biconcave discs, the boundaries and surface features of the flat planar oriented biconcave discs allows for ready discrimination of the orientation required for utilizing a particular cell for image analysis.
- a simple criterion incorporated in the image processing algorithm identifies red blood cells as acceptable for further analysis.
- Such criterion could require that the maximum diameters in the X and Y axes differ by no more than + 2%. Consistent deviation from this criteria would indicate important morphological abnormalities such as poikilocytosis or sickle cell anemia, and would generate a report notation that further examination of this patient is appropriate.
- Analytical programs for image analysis, computation and presentation of results can be permanently stored in the memory of the computer. Given the very great number of cells flowing past the visualized field in any instant, there will be sufficient numbers conforming to the strict orientation criteria discussed above such that analysis of cells having the same uniform special orientation can be selected for quantitative analysis. This analysis will produce a direct measured value for the cell volume of each imaged cell. When this number is averaged over numerous cells, the MCV is acquired through direct measurement.
- This MCV value, determined in vivo will be more accurate than that approximately calculated utilizing _in vitro analysis of blood samples obtained through phlebotomy.
- these values for MCV can be made equivalent by obtaining samples of blood simultaneously with measurements made by the new apparatus. Comparison of a great number of these values will establish an empirical correlation from which calculation algorithms can then be incorporated into computer to assure that the values yielded by the instrument will correspond to those values currently generated by jln vitro instrumentation. This will serve to avoid confusion and provide the physician with values in a familiar range.
- Hct hematocrit
- Hb hemoglobin concentration
- MCHC mean cell hemoglobin concentration
- the computer will accumulate the results of the numerous analyses discussed above and will perform statistical analysis to compute the mean, and coefficients of variation for each measured parameter.
- This primary data is stored for various visual displays, such as for example histograms or other pictorial representations of the cell analysis or the cells themselves.
- the computer will store the above measured , c and calculated indices for printout, display or uploading to a larger computer, for example a laboratory or hospital computer or may store.the data for later statistical analysis.
- the apparatus may optionally include conventional peripheral devices
- the Output Device 52 can be any appropriate instrumentation such as CRTs, VDTs or printing
- 25 devices wherein the results of the red blood cell analysis can be provided either on screen or hard copy. It is preferably capable of holding data for immediate viewing, printing or transmission.
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US88630686A | 1986-07-15 | 1986-07-15 | |
US886306 | 1986-07-15 |
Publications (2)
Publication Number | Publication Date |
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EP0274521A1 true EP0274521A1 (de) | 1988-07-20 |
EP0274521A4 EP0274521A4 (de) | 1988-11-16 |
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Application Number | Title | Priority Date | Filing Date |
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EP19870905049 Withdrawn EP0274521A4 (de) | 1986-07-15 | 1987-07-09 | Testverfahren -i(in vivo) für erythrozytenindices. |
Country Status (3)
Country | Link |
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EP (1) | EP0274521A4 (de) |
JP (1) | JPH01502563A (de) |
WO (1) | WO1988000447A1 (de) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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AU608807B2 (en) * | 1987-03-03 | 1991-04-18 | Hitoshi Fujii | Apparatus for monitoring bloodstream |
US5598842A (en) * | 1993-09-03 | 1997-02-04 | Toa Medical Electronics Co., Ltd. | Non-invasive blood analyzer and method using the same |
JP3364323B2 (ja) * | 1994-05-17 | 2003-01-08 | 謙 石原 | 非侵襲血液分析装置 |
AP931A (en) * | 1995-10-23 | 2001-02-02 | Cytometrics Inc | Method and apparatus for reflected imaging analysis. |
AU738223B2 (en) * | 1995-10-23 | 2001-09-13 | Cytometrics, Inc. | Method and apparatus for reflected imaging analysis |
US6305804B1 (en) | 1999-03-25 | 2001-10-23 | Fovioptics, Inc. | Non-invasive measurement of blood component using retinal imaging |
US6650915B2 (en) | 2001-09-13 | 2003-11-18 | Fovioptics, Inc. | Non-invasive measurement of blood analytes using photodynamics |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3736918A (en) * | 1970-10-02 | 1973-06-05 | Woog Inst Rech | Method and apparatus for in vivo measuring blood velocity in capillaries |
DE3328862A1 (de) * | 1982-09-16 | 1985-02-28 | Siemens AG, 1000 Berlin und 8000 München | Verfahren und vorrichtung zur gewebefotometrie, insbesondere zur quantitativen ermittlung der blut-sauerstoff-saettigung aus fotometrischen messwerten |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5493890A (en) * | 1977-12-30 | 1979-07-25 | Minolta Camera Kk | Eyeeground oximeter |
US4194217A (en) * | 1978-03-31 | 1980-03-18 | Bosch Francois J G Van Den | Method and apparatus for in-vivo spectroscopic analysis |
JPS55133239A (en) * | 1979-04-05 | 1980-10-16 | Olympus Optical Co | Microscope for blood vessel |
-
1987
- 1987-07-09 EP EP19870905049 patent/EP0274521A4/de not_active Withdrawn
- 1987-07-09 JP JP62504479A patent/JPH01502563A/ja active Pending
- 1987-07-09 WO PCT/US1987/001644 patent/WO1988000447A1/en not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3736918A (en) * | 1970-10-02 | 1973-06-05 | Woog Inst Rech | Method and apparatus for in vivo measuring blood velocity in capillaries |
DE3328862A1 (de) * | 1982-09-16 | 1985-02-28 | Siemens AG, 1000 Berlin und 8000 München | Verfahren und vorrichtung zur gewebefotometrie, insbesondere zur quantitativen ermittlung der blut-sauerstoff-saettigung aus fotometrischen messwerten |
Non-Patent Citations (4)
Title |
---|
ARCH. OPHTHALMOL., vol. 96, May 1978, pages 893-897; J.G. CUNHA-VAZ et al.: "Studies on retinal blood flow. Estimation of human retinal blood flow by slit-lamp fluorophotometry" * |
MICROVASCULAR RESEARCH, vol. 20, 1980, pages 1-8, Academic Press, Inc., US; K. TYMI et al.: "A method for on-line measurements of red cell velocity in microvessels using computerized frame-by-frame analysis of television images" * |
MICROVASCULAR RESEARCH, vol. 5, 1973, pages 351-356, Academic Press, Inc., US; P.C. JOHNSON et al.: "Measurement of capillary hematocrit by photometric techniques" * |
See also references of WO8800447A1 * |
Also Published As
Publication number | Publication date |
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JPH01502563A (ja) | 1989-09-07 |
WO1988000447A1 (en) | 1988-01-28 |
EP0274521A4 (de) | 1988-11-16 |
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