Source: https://patents.google.com/patent/US20040054268A1/en
Timestamp: 2019-04-25 01:23:07+00:00

Document:
An optoacoustic apparatus is disclosed which includes a radiation source of pulsed radiation and a probe having a front face to be placed in contact with a tissue site of an animal body. The probe further includes an optical fiber terminating at the surface of the front face of the probe and connected at their other end to a pulsed laser. The front face of the probe also has mounted therein or thereon a piezoelectric transducer for detecting an acoustic response to the radiation pulses connected to a processing unit which converts the transducer signal into a measure of hemoglobin concentration and/or hematocrit of blood.
where μ a(r) is the absorption coefficient in the tissue, Φ(r) is the fluence distribution in the tissue, ρ is the tissue density, and Cv is the heat capacity at constant volume. The formula shown in equation (2) is valid upon irradiation condition of heat confinement, which means that insignificant heat diffusion occurs during laser pulse excitation.
Irradiation conditions of temporal pressure confinement can usually be achieved by irradiating the sample with laser pulses having a pulse width having a nanosecond duration. The exponential factor exp(−μ az) represents the exponential attenuation of the optical radiation in the medium due to absorption. According to equation (3) optoacoustic pressure is proportional to the Grüneisen parameter, fluence, and absorption coefficient of the medium. Equation (3) is valid for blood when the blood is irradiated with laser light in the visible and near-infrared spectra because the absorption coefficient of blood is greater than or close to the reduced scattering coefficient, μ's=μs(1 −g), where μs is the scattering coefficient and g is the anisotropy factor . The apparatus and methods of this invention are based on the fact that the absorption coefficient of blood is proportional to hemoglobin concentration. Therefore, both the amplitude and slope of the generated optoacoustic pressure induced in blood are dependent on hemoglobin concentration.
and characterizes light penetration in tissue . Light penetration depth is defined as 1/μ eff. Absorption and scattering coefficients of tissues are low in the near-infrared spectral range (from about 600 to about 1300 nm) resulting in deeper penetration of near-infrared radiation compared with light in other parts of the electromagnetic spectrum. Near-infrared radiation is the preferred spectral range for the apparatuses and methods of this invention because near-infrared light allows sufficient light penetration into a tissue for effective optoacoustic monitoring of hemoglobin concentration within the tissue including a blood vessel.
Similar experiments and calculations were performed when blood was irradiated through a turbid gelatin slab with the thickness of 1 cm. The gelatin slab had optical properties similar to that of tissues in the near infrared spectral range (μ a=0.6 cm−1 and μs '=2.9 cm−1) and can be used to simulate a tissue layer in vivo. The results presented in FIGS. 4, 5, and 6 indicate that the addition of the turbid slab did not decrease the accuracy of the blood Hb concentration measurements. The amplitude of the signals is close to that recorded from blood irradiated without the gelatin slab despite attenuation, because scattering in the slab resulted in an increase of irradiated blood area and, therefore, an increase in optoacoustic signal amplitude.
Experiments were also performed with an aqueous solution colored with an absorbing dye (naphthol green) simulating blood. The experiment demonstrated similar results to the previous experiments as shown in FIGS. 7, 8,  9.
To monitor hemoglobin concentration and hematocrit in vivo, irradiation of tissue by laser light and detection the laser-induced optoacoustic waves should generally be performed from the same side of the tissue. The inventors designed, built, and, tested different optoacoustic probes: (1) with a ring shape piezoelectric element and optical fiber in the center of the ring (see FIG. 10A); (2) with optical fibers surrounding a disc shaped piezoelectric element (see FIG. 10B); and (3) with optical fibers adjacent to a disc shaped piezoelectric element (see FIG. 10C). Each of these configurations has advantages and each used a PVDF based transducer. The most preferable probe configuration for hemoglobin monitoring includes a ring shaped piezoelectric element with optical fibers in the center of the ring as shown in FIG. 10A. The results of tests of the probe of FIG. 10A are presented below. Looking at FIGS.  10A-C, a probe generally 100 is shown to include a housing 102 which can be composed of metal or other structural material such as plastic, an optical system 104, a backing element 106, a piezoelectric element 108 and an isolating layer 110. The optical system 104 includes an optical fiber 112, an optical screen 114 and an acoustic screen 116. The system 104 would connect at its proximal end to a pulsed light source such as a laser (not shown), while its distal end 118 terminates flush with the housing 102 at the probe's distal end 120. The probe of FIG. 10A has the optical system 104 passing through a center 122 of a ring-shaped piezoelectric element 108. The probe of FIG. 10B has the optical system 104 distributed around a disk shaped piezoelectric element 108. And, the probe of FIG. 10C has the optical system 104 positions next to (a side-by-side arrangement) the piezoelectric element 108 which can be of any desired shape.
Referring now to FIGS. 10D and E, two preferred embodiments of esophagus probes  200 is shown to includes a housing 202 which can be composed of metal or other structural material such as plastic, an optical system 204, a backing element 206, a piezoelectric element 208 and an isolating layer 210. The optical system 204 includes an optical fiber 212, an optical screen 214 and an acoustic screen 216. The system 204 would connect at its proximal end to a pulsed light source such as a laser (not shown), while its distal end 218 terminates flush with the housing 202 at the probe's distal end or tip 220. The probe of FIG. 10D has the optical system 204 passing through a center 222 of a ring-shaped piezoelectric element 208. The probe of FIG. 10B also has the optical system 204 passing through the center 220 of a ring-shaped piezoelectric element 208, but the distal end 218 of the optical system 204, the transducer 208 and the isolating layer 210 so that the tip 220 is oriented at a right angle to the main body 224 of the probe 200. Of course, the tip 220 can be oriented at any angle relative to the main body 224 provided that the tip 220 can contact the esophagus wall adjacent the aorta.
Referring now to FIG. 13, optoacoustic signals recorded from a phantom (2.2-mm plastic tube in a turbid solution) simulating radial artery are shown. The absorbing solution in the tube had an absorption coefficient of about 2 to about 24 cm −1. The first peak at about 1.2 μs is a signal induced in the housing of the probe and the turbid solution. The signals induced in the tube start at about 3 μs representing time of flight of the optoacoustic waves from the upper surface of the tube to the probe. Both amplitude and temporal profile of the signals induced in the tube are dependent on the solution absorption coefficient. The optoacoustic signal amplitude increases gradually with absorption coefficient as shown in FIG. 14. The signal from the solutions with high absorption coefficient values has two positive peaks, while only one positive peak is recorded from solutions with low absorption coefficient values. The optoacoustic signals were normalized and their first derivatives (slope) were calculated. The slope of the signals at about 5 μs is the most sensitive to changes in the absorption coefficient as shown in FIG. 15. It is positive for solutions with high absorptions and negative for ones with low absorptions. The measurement and calculation of the slope can be used to provide accurate measurement of blood Hb concentrations.
Referring now to FIG. 16, the optoacoustic signals recorded at different axial distance between the tube and the probe for solution with an absorption coefficient of about 13 cm 1 are shown. The variation of the distance simulated different thicknesses of tissue between the probe and a simulated artery (radial, carotid, or femoral). The position of the signal changes with the distance indicating the depth of the artery in the solution, i.e., its location in a tissue. The temporal profile of the signals change slightly with depth while the signal amplitude sharply decreases with increasing depth due to stronger attenuation of light and propagation of the optoacoustic signals from the cylindrical source as shown in FIG. 17. Lateral displacement of the probe with respect to the tube changes both amplitude and profile of the signals as shown in FIGS. 18 and 19. These data indicate that lateral alignment of the probe is important for accurate measurement of Hb concentration. Thus, by laterally scanning the optoacoustic probe on the skin surface, the practitioner can obtain highly accurate Hb concentration measurements, where the scanning is used to maximize the measuring process—maximize signal amplitude.
1. Goodnough L T. Brecher M E. Kanter M H. AuBuchon J P. Transfusion medicine. Second of two parts—blood conservation.  New England Journal of Medicine. 340(7):525-33, 1999.
2. Goodnough L T. Brecher M E. Kanter M H. AuBuchon J P. Transfusion medicine. First of two parts—blood transfusion.  New England Journal of Medicine. 340(6):438-47, 1999.
3. Silver M J. Li Y H. Gragg L A. Jubran F. Stoller J K. Reduction of blood loss from diagnostic sampling in critically ill patients using a blood-conserving arterial line system.  Chest. 104(6):1711-5, 1993.
4. Zimmerman J E. Seneff M G. Sun X. Wagner D P. Knaus W A. Evaluating laboratory usage in the intensive care unit: patient and institutional characteristics that influence frequency of blood sampling.  Critical Care Medicine. 25(5):737-48, 1997.
5. Henry M L. Garner W L. Fabri P J. latrogenic anemia.  American Journal of Surgery. 151(3).362-3, 1986.
6. Foulke G E. Harlow D J. Effective measures for reducing blood loss from diagnostic laboratory tests in intensive care unit patients.  Critical Care Medicine. 17(11):1143-5, 1989.
7. Smoller B R. Kruskall M S. Phlebotomy for diagnostic laboratory tests in adults. Pattern of use and effect on transfusion requirements.  New England Journal of Medicine. 314(19):1233-5, 1986.
8. Tanaka Y. Morimoto T. Watari H. Miyazaki M. Continuous monitoring of circulating blood hematocrit.  Japanese Journal of Physiology. 26(4):345-53, 1976.
9. Kaiwa T. Mori T. Kijima T. Nogawa M. Nojiri C. Takatani S. Measurement of blood hematocrit inside the magnetically suspended centrifugal pump using an optical technique: application to assessment of pump flow.  Artificial Organs. 23(6):490-5, 1999.
10. Jabara A E. Mehta R L. Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor.  ASAIO Journal. 41(3).M682-7, 1995.
11. Ronco C, Brendolan A, and Bellomo R. Online monitoring in continuous renal replacement therapies.  Kidney International. 36, Suppl. 72, S-8-S-14, 1999.
12. Maasrani M. Jaffrin M Y. Boudailliez B. Continuous measurements by impedance of haematocrit and plasma volume variations during dialysis.  Medical & Biological Engineering & Computing. 35(3):167-71, 1997.
13. Esenaliev R. O., Oraevsky A. A., Letokhov V. S., Karabutov A. A., Malinsky T. V. Studies of Acoustical and Shock Waves in the Pulsed Laser Ablation of Biotissue.  Lasers Surg. Med., 1993, v. 13, pp.470-484.
14. Oraevsky A. A., Jacques S. L., Esenaliev R. O., Tittel F. K. Imaging in layered tissues using time-resolved detection of laser-induced stress transients.  SPIE Proc. 1994, v. 2134, pp. 122-128.
15. Oraevsky A. A., Esenaliev R. O., Jacques S. L., Tittel F. K. Laser opto-acoustic tomography for medical diagnostics: principles.  SPIE Proc. 1996, v. 2676, pp. 22-31.
16. Esenaliev R. O., Oraevsky A. A., Jacques S. L., Tittel F. K. Laser opto-acoustic tomography for medical diagnostics: Experiments with biological tissues.  SPIE Proc. 1996, v. 2676, pp. 84-90.
18. Oraevsky A. A., Esenaliev R. O., Karabutov A. A. Optoacoustic Imaging in Layered Tissues: Signal Processing.  SPIE Proc. 1997, v. 2979, pp. 59-70.
19. Esenaliev R. O., Karabutov A. A., Tittel F. K., Fomage B. D., Thomsen S. L., Stelling C., Oraevsky A. A. Laser Optoacoustic Imaging for Breast Cancer Diagnostics: Limit of Detection and Comparison with X-ray and Ultrasound Imaging.  SPIE Proc. 1997, v. 2979, pp. 71-82.
20. Esenaliev R. O., Alma H., Tittel F. K., Oraevsky A. A. Axial resolution of laser optoacoustic imaging: Influence of acoustic attenuation and diffraction.  SPIE Proc. 1998, v. 3254, pp. 294-301.
22. Oraevsky A. A., Andreev V. G., Karabutov A. A., and Esenaliev R. O. Two-Dimensional Opto-Acoustic Tomography Transducer Arrey and Image Reconstruction Algorithm.  SPIE Proc. 3601:256-267, 1999.
23. Oraevsky A. A, Andreev V. G., Karabutov A. A., Fleming D. R., Gatalica Z., Singh H., and Esenaliev R. O. Laser Opto-Acoustic Imaging of the Breast: Detection of Cancer Angiogenesis.  SPIE Proc. 3597, 1999, pp. 256-267.
27. Esenaliev R. O., Larin K. V., Larina I. V., Motamedi M., Oraevsky A. A. Optical properties of normal and coagulated tissues: Measurements using combination of optoacoustic and diffuse reflectance techniques.  SPIE Proc. 1998, v. 3726, pp. 560-566.
28. Esenaliev R. O., Larina I. V., Larin K. V, Motamedi M, Karabutov A A, Oraevsky A A. Laser Optoacoustic Technique for Real-Time Measurement of Thermal Damage in Tissues.  SPIE Proc. 3594, 1999, pp.101-113.
29. Esenaliev R. O., Oraevsky A. A., Larin K. V., Larina I. V., Motamedi M. Real-Time Optoacoustic Monitoring of Temperature in Tissues.  SPIE Proc. 3601:268-275, 1999.
a processing unit connected to the distal end of the cable for converting the transducer output into a measure of blood hemoglobin concentration and/or hematocrit.
2. The apparatus of claim 1, wherein the radiation source is a laser and the pulses are of a nanosecond duration.
3. The apparatus of claim 1, wherein the hemoglobin is associated with blood in a blood vessel or tissue site.
a cable connected to the transducer at its proximal end and exiting the probe out of the back portion of the probe.
analyzing a temporal profile and/or amplitude of the optoacoustic wave with a data processing unit including software adapted to convert the acoustic detector data into data representing a hemoglobin concentration in blood.
an electronic signal recording and processing system connected to the cable, where the signal recording and processing system includes a digital processing unit or computer calculating a hemoglobin concentration from the recorded optoacoustic pressure profiles and amplitudes.
7. The system of claim 6, wherein the source produces light pulses in the spectral range from about 400 to about 2500 nm.
8. The system of claim 6, wherein the source comprises two sources having producing light pulses of different wavelengths.
9. The system of claim 6, wherein the source comprises a laser.
10. The system of claim 6, wherein the vessel comprises an aorta and wherein the probe inserted into an esophagus and the irradiation occurs through the esophagus wall adjacent the arota.
11. The system of claim 6, wherein the vessel comprises a radial artery.
12. The system of claim 6, wherein the vessel comprises a carotid artery.
13. The system of claim 6, wherein the vessel comprises a brachial artery.
14. The system of claim 6, wherein the vessel comprises a femoral artery.
15. The system of claim 6, wherein the vessel comprises an artery.
16. The system of claim 6, wherein the vessel comprises a vein.
17. The system of claim 6, wherein the vessel comprises a vein under the skin or in a hollow organ.
18. The system of claim 17, wherein the light pulses have a wavelength of about 548, 568, 587, 805 nm or mixture or combinations thereof or the wavelength is in spectral ranges from about 400 to about 640 or above about 1120 nm where an absorption coefficient of oxy- and deoxygenated blood are similar so that the hemoglobin concentration can be derived from both oxygenated and deoxygenated blood.
19. The system of claim 6, wherein the source comprises a Nd:YAG laser or a tunable laser or an optical parametric generator or mixtures or combinations thereof.
20. The system of claim 19, wherein the tunable lasers comprises a Ti:Sapphire laser or a dye laser or mixtures or combinations thereof.
21. The system of claim 6, wherein the system is used for hematocrit measurements in the spectral range from 400 to 2500 nm and preferably in the spectral range above 1350 nm where optoacoustic signal characteristics are more sensitive to the changes in blood scattering and, therefore, to changes in hematocrit.
22. The system of claim 6, wherein the system is used for blood volume measurements.
23. The system of claim 6, wherein the system is used for ultrasound-guided optoacoustic monitoring of fetal anemia during pregnancy.
24. The system of claim 6, wherein the system is used for measuring hematocrit and a hemoglobin concentration in cord blood.
25. The system of claim 6, wherein the system is used for hemoglobin concentration monitoring in patients with kidney failure or patients on dialysis.
DE3576219D1 (en) 1984-10-16 1990-04-05 Fuji Photo Film Co Ltd Acousto-optical image deformation.
NO880891L (en) 1987-03-03 1988-09-05 Elizabeth May Dowling Method and apparatus for measuring or detecting the concentration of a substance.
FR2712697B1 (en) 1993-11-19 1995-12-15 Commissariat Energie Atomique A method of elemental analysis by optical emission spectrometry on laser produced plasma in the presence of argon.

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