Advances in photoacoustic noninvasive glucose testing.HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. and hepatitis, may be transmitted by bodily fluids, the need for noninvasive measurement techniques that eliminate the risk of contamination also increases. In addition, the elimination of pain in the measurement process and the potential for continuous measurement are also key factors. The noninvasive measurement of blood glucose blood glucose Diabetology The principal sugar produced by the body from food–especially carbohydrates, but also from proteins and fats; glucose is the body's major source of energy, is transported to cells via the circulation and used by cells in the presence in particular is of great individual and economic importance because of the large population of diabetics who require regular and accurate information regarding their blood glucose concentrations.
In 1997, it was reported (1) that there were more than 120 million diabetics world-wide; this number is predicted to increase to more than 220 million by the year 2010. Diabetes mellitus diabetes mellitus
Disorder of insufficient production of or reduced sensitivity to insulin. Insulin, synthesized in the islets of Langerhans (see Langerhans, islets of), is necessary to metabolize glucose. In diabetes, blood sugar levels increase (hyperglycemia). is a complicated and serious condition and is one of the most prevalent noncommunicable diseases in the world. Successful management of diabetes involves knowledge of the current blood glucose concentration to allow the diabetic to compensate by diet, oral medication, or insulin injections. Without knowledge of the blood glucose concentration, the correct treatment is not possible and serious complications affecting internal organs, circulation, and eyesight may occur.
The current methods of measuring blood glucose concentrations require the diabetic to obtain a blood sample for analysis by a test strip. According to a recent 9-year study, The Diabetes Control and Complications Trial The Diabetes Control and Complications Trial, or DCCT, was the largest, most comprehensive diabetes study ever conducted at the time.
The U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducted this clinical study of 1,441 volunteers (2), optimum treatment for a diabetic requires regular blood glucose measurements; however, the discomfort experienced by users means that present methods are not being used by diabetics with sufficient regularity. There are indications (3) that the use of spot check measurements does not provide adequate information for optimal glucose control, and there is a strong case for more frequent or "continuous" measurements. This type of measurement would also yield the rate of change of glucose, which would allow planning of the appropriate insulin dose or dietary content.
The measurement of blood glucose by any technique is inherently complex because of the wide range of potentially interfering components. For a noninvasive technique, not only are there many analytes within human blood that could interfere with the measurement, but there are also other problems such as the variability and inhomogeneity in·ho·mo·ge·ne·i·ty
n. pl. in·ho·mo·ge·ne·i·ties
1. Lack of homogeneity.
2. Something that is not homogeneous or uniform.
Noun 1. of human skin and the constantly changing human physiology.
Research into new, less painful methods of measurement has been carried out for several decades, and several reviews on the subject have been published (4-6). The two most popular techniques being attempted are measurement of the change in optical transmission or polarization rotation attributable to the presence of glucose. In transmission configurations, the intensity of light transmitted at several wavelengths is used to determine glucose concentrations. Transmission spectroscopy is susceptible to light scattering in tissue and is technically limited by the requirement of fixed, diametrically di·a·met·ri·cal also di·a·met·ric
1. Of, relating to, or along a diameter.
2. Exactly opposite; contrary.
di opposed, positioning of light source and detector. Transmission measurements have been carried out on the skin (7) and on animal and human eyes (8), making use of the correlation between blood glucose concentration and the glucose concentration of the aqueous humor aqueous humor
The clear, watery fluid circulating in the chamber of the eye between the cornea and the lens.
Aqueous humor in the eye. Optical rotation optical rotation: see polarization of light. of polarized light in the aqueous humor of the eye (9-12) has also been investigated. Other researchers have carried out in vitro tests using Raman spectroscopy (13-16), fluorescence studies (17) and Fourier-transform infrared spectroscopy (18-20). The human lip has been used as a location for glucose measurements using techniques including diffuse reflectance (21) and attenuated total reflectance Attenuated total reflectance (ATR) is a sampling technique used in conjunction with infrared spectroscopy which enables samples to be examined directly in the solid or liquid state without further preparation. (22). The latter technique has also been used for tests on the finger (23).
Other noninvasive approaches attempt to use a correlation between glucose content in interstitial fluid interstitial fluid
The fluid in spaces between the tissue cells.
The fluid between cells in tissues. Referred to as the liquid subtance of the body.
Mentioned in: Lymphedema and capillary blood (24). The use of a patch or reservoir on the skin surface to collect glucose has also been explored (25).
In this report, we discuss the alternative technique of pulsed laser photoacoustic spectroscopy. In this technique, short pulses of laser light are directed into the tissue. The resulting acoustic signal depends on the optical and physical characteristics of the sample and may be the basis of determining blood glucose concentrations noninvasively.
Recent developments in optoelectronic technologies give the photoacoustic method of measurement the potential for portability and long component life with the use of piezoelectrics and compact electronics and diode lasers with levels of optical radiation that are several orders of magnitude below pain or tissue damage thresholds.
The photoacoustic process involves the conversion of optical energy into acoustic energy by a multistage energy conversion process. The fraction of incident optical energy that is absorbed is determined by the optical absorption coefficient absorption coefficient
1. The milliliters of a gas at standard temperature and pressure that will saturate 100 milliters of liquid.
2. The amount of light absorbed in 1 atom or in 1 unit of thickness or mass of a given substance. . The absorbed energy may then be dissipated by radiative processes in which light is re-emitted from the sample or by nonradiative processes in which the absorbed energy leads to localized heating of the sample. In the latter case, this produces a small temperature rise, which is characterized by the specific heat capacity and in turn leads to volumetric volumetric /vol·u·met·ric/ (vol?u-met´rik) pertaining to or accompanied by measurement in volumes.
Of or relating to measurement by volume. thermal expansion of the optical interaction region. The resulting dimensional change and associated pressure pulse are the basis of the thermoelastic photoacoustic generation. This ultrasonic pressure pulse propagates from the generation region and can then be measured by a piezoelectric The property of certain crystals that causes them to produce voltage when a mechanical pressure is applied to them such as sound vibrations. This technique is used to build crystal microphones, phonograph cartridges and strain gauges, all of which turn mechanical movement into voltage. detector.
The photoacoustic pulse consists of an isolated pressure wave comprising a compressive com·pres·sive
Serving to or able to compress.
com·pressive·ly adv. pulse followed by a rarefaction rarefaction /rar·e·fac·tion/ (rar?i-fak´shun) condition of being or becoming less dense.
n. . Generally, the peak-to-peak amplitude of the detected photoacoustic pulse is used for analysis and is directly proportional to the absorbed energy. Accordingly, an energy measurement is used to normalize normalize
to convert a set of data by, for example, converting them to logarithms or reciprocals so that their previous non-normal distribution is converted to a normal one. the peak-to-peak measurement. A typical photoacoustic signal is shown in Fig. 1. The lower trace is the optical signal, and the upper trace is the photoacoustic signal. A time delay between the optical pulse and the photoacoustic pulse is evident. This time delay is attributable to the propagation of the photoacoustic pulse from the acoustic source to the detector and can be used for velocity of sound measurements or to determine the location of the acoustic source in imaging techniques.
The generated pressure in the photoacoustic process can be described by the following wave equation, where electrostriction (26) is ignored:
[1/[[upsilon up·si·lon or yp·si·lon
Symbol The 20th letter of the Greek alphabet. ].sup.2] [[partial derivative].sup.2]/[[partial derivative]t.sup.2] - [[gradient].sup.2]] p l = [alpha][beta]/[C.sub.p] [partial derivative]I/[partial derivative]t
where I is the intensity of the laser light, v is the sound velocity in the medium, a is the optical absorption coefficient, [beta] is the coefficient of volumetric thermal expansion, [C.sub.p] is the specific heat capacity, and p(r,t) is the acoustic pressure.
For a weakly absorbing sample, the peak pressure P can be described (27,28) by the following equation:
P = k [[beta][upsilon].sup.n]/[C.sub.p] [E.sub.o][alpha]
where k is a system constant, [E.sub.o] is the incident laser pulse energy, and n is a constant between one and two, depending on the particular experimental conditions.
In some cases, the combination of physical parameters gives an enhancement of the photoacoustic response compared with the response in conventional spectroscopy, and this can be exploited, for example, in the detection of hydrocarbons in water (29, 30). The response to glucose, however, does not give substantial photoacoustic signal enhancement.
Photoacoustics have been used to obtain information about the concentrations of species, including the monitoring of trace gas concentrations (31-34), medical applications such as the detection of cancer (35, 36), and investigations into skin structure (37) and chemical penetration in the skin (38). Photoacoustics has also been used for lateral and depth imaging (35,36,39-44) and has applications in other medical and biological areas, including the determination of melanin melanin (mĕl`ənĭn), water-insoluble polymer of various compounds derived from the amino acid tyrosine. It is one of two pigments found in human skin and hair and adds brown to skin color; the other pigment is carotene, which contributes in human hair (45) and investigations into the diffusion of chromophores in human skin (46).
[FIGURE 1 OMITTED]
To assess the feasibility of photoacoustic noninvasive blood glucose detection, the technique was first used for in vitro studies in the mid-infrared region with both aqueous glucose solutions and human whole blood (47). Within the wavelength region of 9.564-9.694 [micro]m, it was shown that the optimum wavelength for glucose detection was 9.676 [micro]m. At the wavelength 9.676 [micro]m, aqueous glucose solutions of 8.3-426 mmol/L (149-7670 mg/dL) were investigated, and at glucose concentrations <33 mmol/L (600 mg/dL), a linear relationship was shown.
Although previous work in the mid-infrared region demonstrated the potential of photoacoustics as a method of measuring glucose concentrations, this wavelength region is not regarded as viable for human tissue studies because of the high water absorption that reduces penetration depths to microns. This penetration may not be sufficient to investigate blood constituents within human tissue, although interaction with interstitial fluid yields measurements that correlate with blood glucose concentrations but with a time shift (48).
The spectral region that shows the most promise for absorption by the analytes within blood is within the "tissue window", around the 1-2 /,m region (49). Although measurements within this region are advantageous for tissue studies, they coincide with a region of lower glucose absorption. Initial results with pulsed photoacoustics achieved glucose concentration measurements within this region in aqueous solutions (50), gelatin gelatin or animal jelly, foodstuff obtained from connective tissue (found in hoofs, bones, tendons, ligaments, and cartilage) of vertebrate animals by the action of boiling water or dilute acid. phantoms (51), and blood samples (52).
Aqueous glucose solutions in the concentration range 1.7-33 mmol/L (30-600 mg/dL) have been used for in vitro measurements in this tissue window spectral region (49). The percentage of change in the photoacoustic response of the glucose solutions was compared with that of water at a wavelength of 1700 nm. A linear relationship, y = 0.21x - 0.02 with a correlation coefficient Correlation Coefficient
A measure that determines the degree to which two variable's movements are associated.
The correlation coefficient is calculated as: of 0.99 was obtained, where x is the glucose concentration and y is the percentage of change of the photoacoustic response from that of water.
Photoacoustic measurements in a gelatin-based tissue phantom (51) have also shown a linear correlation when a wavelength of 1.064 /,m is used to investigate glucose concentrations between 1 and 100 mmol/L (180 and 18 000 mg/dL). At this wavelength, there was a 71% change in the photoacoustic signal over the above concentration range.
In vitro photoacoustic investigations of blood plasma blood plasma
The yellow or gray-yellow, protein-containing fluid portion of blood in which the blood cells and platelets are normally suspended. and human whole blood samples within the glucose concentration range 0.56-10 mmol/L (10-1800 mg/dL) have also been investigated (47,53) and gave a linear correlation between the glucose concentration and the change in the photoacoustic response at 1180 and 1700 nm. Preliminary in vivo studies have also been undertaken to assess the feasibility of photoacoustics as a noninvasive technique on humans (49).
Eight consenting volunteers were studied under a protocol, which was approved by the local ethics committee ethics committee A multidisciplinary hospital body composed of a broad spectrum of personnel–eg, physicians, nurses, social workers, priests, and others, which addresses the moral and ethical issues within the hospital. See DNR, Institutional review board. . Four nondiabetic subjects, two type 2 diabetics (noninsulin-dependent), and two type 1 diabetics (insulin-dependent) were studied.
The non-diabetic and type 2 volunteers fasted from the previous evening, and the type 1 diabetic volunteers omitted their morning insulin. Non-diabetic and type 2 diabetic volunteers received a standard 75-g n-glucose load orally. The blood glucose concentration of the type 1 diabetics was controlled by administration of insulin, and all subjects with higher than normal blood glucose concentrations were monitored until their blood glucose concentration fell to normal values normal values
A set of laboratory test values used to characterize apparently healthy individuals, now replaced by reference values. . The subject was seated throughout the procedure with the right index fingers immobilized in a mount. The laser pulse was incident on the side of the finger through an optical fiber, and the photoacoustic signal was detected from the pad of the finger, which was in contact with the piezoelectric transducer.
A near-infrared pulsed laser source (30) was utilized in the in vivo studies. A piezoelectric transducer detected the photoacoustic pulses, and the resulting signals were acquired with a similar set-up as described in the in vitro studies discussed later. The mean photoacoustic signals were acquired over a 5-s period at intervals of 5 min.
Reference blood samples were taken at 10-min intervals, and blood glucose concentrations were measured using a Yellow Springs Instruments analyzer (YSI YSI Yousendit (File Transfer Website)
YSI Youth Science Institute
YSI You Stupid Idiot 23000). In addition, blood glucose concentrations from the diabetic subjects were monitored periodically during the tests using an Exactech Companion 2 meter and test strips.
The photoacoustic data presented in Fig. 2 are based on the measurement of the peak-to-peak amplitude of the photoacoustic signal, with a correction for linear system drift, which may be attributable to physiological factors as a result of the subject being immobilized throughout the observations. The CV in the reference measurement of the blood glucose concentration was 3%, and that in the photoacoustic response varied between 1% and 5%, depending on the initial instrument gain settings.
In Vivo Results
Three key results from these tests, which were previewed earlier (52), are shown in Fig. 2, which shows the change in both the glucose concentration and the photoacoustic response throughout the duration of the test. In each case, there was good correlation (r2 >0.84) between the photoacoustic measurement and the measured glucose concentration. The gradient and the offset differed in each case, which may have been attributable to a combination of both instrumental settings and person-to-person variables, which will be investigated in future work. The results, however, did allow a predicted glucose concentration to be calculated from the photoacoustic measurements, using the individual linear regressions.
The results for all of the measurements, at 10-min intervals, when both clinical and photoacoustic measurements were available for all eight subjects are shown in Fig. 3. This shows a linear correlation of 0.96 between the predicted and the clinical glucose concentration.
We recognize that this is a favorable presentation of the results, and a more realistic representation of the data can be seen through analysis of the percentage of change of the predicted glucose concentration from the clinical measurement. The results of this analysis are presented in Fig. 4, which shows that ~91% of the data points lie within [+ or -] 20% of the clinical glucose concentration, corresponding to zone A in a Clarke (54) error grid analysis.
Current In Vitro Studies
In the preceding sections, the only variable under consideration was glucose. To explore the more realistic physiological picture, an in vitro investigation of the effect of other blood analytes was undertaken. The in vitro studies described here were designed to investigate the wavelength dependence of the photoacoustic signals from glucose in the presence of several common blood analytes. There are numerous analytes within the blood, and three were chosen for this initial study, sodium chloride sodium chloride, NaCl, common salt. Properties
Sodium chloride is readily soluble in water and insoluble or only slightly soluble in most other liquids. It forms small, transparent, colorless to white cubic crystals. , cholesterol, and bovine serum albumin serum albumin
See seralbumin. (BSA 1. BSA - Business Software Alliance.
2. BSA - Bidouilleurs Sans Argent. ).
A tunable MOPO-710 laser system (Spectra Physics), pumped by the third harmonic of a Nd:YAG laser, was used as the optical source. This provided nearly continuously tunable pulsed optical energy from 400 to beyond 2000 nm, with a pulse duration of approximately 7 ns at a repetition rate of 10 Hz. The optical output was launched into a 2-m length of optical fiber (diameter, 1000 ptm), using a 6-cm focal length lens. The fiber output was directed through a beam splitter at an angle of 45[degrees] to create an energy monitoring channel, and each optical channel was focused into a photoacoustic cell using a 10-cm focal length lens. The sample to be analyzed was contained within the first photoacoustic cell, whereas the presence of a second reference photoacoustic cell provided energy monitoring. For the experiments under consideration here, the energy monitor was provided by the second photoacoustic reference cell containing distilled water, which allowed compensation for variations in incident optical energy and the photoacoustic response to the water spectra.
The voltage pulses from the piezoelectric detector were amplified with a precision AC 9452 amplifier (1MHz (MegaHertZ) One million cycles per second. It is used to measure the transmission speed of electronic devices, including channels, buses and the computer's internal clock. A one-megahertz clock (1 MHz) means some number of bits (16, 32, 64, etc. bandwidth; 100 Mf input impedance; 1 k[omega] output impedance; Brookdeal/EG & G). The resulting signals were digitized by a 125 million samples/ s, dual channel Compu-Scope CS2125 PC plug in card (GaGe Applied Sciences), where the signals were recorded and analyzed. Typically, one photoacoustic measurement resulted from 100 pulses averaged in the software to reduce random noise.
[FIGURE 2 OMITTED]
[FIGURE 3 OMITTED]
Glucose solutions were prepared by dilution of a 1.67 mol/L (30 g/dL) n-glucose stock solution. The glucose concentrations were also cross-referenced with an Abbott-Visionl [TM] clinical chemistry analyzer (Abbott Laboratories).
The spectral region of 800-1200 nm was chosen for these investigations after initial work showed the largest changes with glucose concentration occurred at ~1040 nm.
Photoacoustic responses from the sample and baseline water samples were measured alternately to separate long-term system drifts from changes attributable to the sample concentration. The spectrum of distilled water and a 500 mmol/L (9 g/dL) glucose solution can be seen in Fig. 5. To investigate the changes from the water spectra, the percentages of difference of all the spectra from the baseline water spectrum were calculated. In each of the following studies, the letters a, b, c, d, and e indicate the sequence in which the spectra were obtained.
[FIGURE 4 OMITTED]
The results of this procedure for the glucose spectrum of Fig. 5 can be seen in Fig. 6. The absolute values of the peak wavelengths are inexact in·ex·act
1. Not strictly accurate or precise; not exact: an inexact quotation; an inexact description of what had taken place.
2. in this type of low-resolution experiment, but spectral features may be noted that relate to established spectroscopy of glucose in solution (4). The greatest percentage of change in the photoacoustic response from the glucose sample is in the region of the C--H second overtone at 1126 nm, with a further peak in the region of the second 0--H overtone at 939 nm. These assignments are tentative at this stage and require further investigation. Similarly, in Fig. 6, the reduction in photoacoustic response at 825 nm is within the resolution of the experiment and may be attributable to a displacement effect, but this also requires further investigation.
To investigate the possible contributions of other blood analytes to the total photoacoustic response from blood, solutions of sodium chloride, cholesterol, and BSA were investigated. In this preliminary study, the percentages of change of the photoacoustic signals of the analytes compared with a baseline from water were investigated within the same spectral region as the glucose study. As can be seen from the results, sodium chloride (Fig. 7), cholesterol (Fig. 8), and BSA (Fig. 9) each exhibited a different photoacoustic response.
The photoacoustic response of the sodium chloride solution was distinctly different from the corresponding response of the glucose solution, as shown in Fig. 6. The sodium chloride solution gave a significant increase in the photoacoustic response from 800 to 975 nm. The peak of this response coincides with an overtone band in the water spectrum at 970 nm (55), and the dissolution of NaCl is known to cause a shift of such water bands to longer wavelengths (56). It may also be that the changed physical parameters related to the presence of sodium chloride enhance such changes.
[FIGURE 5 OMITTED]
[FIGURE 6 OMITTED]
The difference in the cholesterol photoacoustic response showed the least spectral features of all four samples, with a basically flat response. However, the sensitivity and resolution in this experiment may be insufficient to show the weak features that have been observed in previous work (57).
The photoacoustic response from the BSA solution showed a small feature at 1050 nm and a significant increase in the photoacoustic response at wavelengths below 900 nm that had not been observed in previous studies (58) and may be attributable to coloration or other contaminants in the sample.
[FIGURE 7 OMITTED]
[FIGURE 8 OMITTED]
This initial study is a precursor to the detailed investigation that will be required before selecting a set of wavelengths on a clear spectroscopic spec·tro·scope
An instrument for producing and observing spectra.
spectro·scop basis that, with appropriate algorithms or other analysis to compensate for the background response from other analytes, may allow the unique determination of glucose concentrations.
There are many analytes within human tissue and body fluids that could interfere with the determination of glucose concentrations in the blood. Three such analytes have been investigated here, sodium chloride, cholesterol, and BSA. From these studies and additional studies of other blood analytes, it may be possible to select wavelengths for discrete glucose concentration measurements. Specific analysis techniques for wavelength selection have not been developed here because the spectroscopic study is not yet complete and we felt that analysis of a complicated system such as tissue and blood based on only a few body analytes would not be fruitful. However, the photoacoustic spectra obtained here show a good indication for the potential use of several wavelengths to specifically monitor glucose in the presence of other body analytes. Previous work (50), as illustrated in Fig. 10, has shown that changes in the photoacoustic response as a result of changes in glucose concentration are insensitive to the presence of specific blood analytes, although the baseline changes substantially. This aspect indicates that multiple wavelength sources will be essential in a viable instrument to give both selectivity of response and baseline correction.
[FIGURE 9 OMITTED]
Because of the complicated nature of both the photoacoustic generation process and the structure and composition of human tissue, it is inevitable that further analysis techniques will be required to eliminate these influences. At present, the analysis of data is carried out using the peak-to-peak value of the photoacoustic response, although the entire signal is recorded. Other methods are under consideration that use the recorded temporal signal, such as Fourier and wavelet (mathematics) wavelet - A waveform that is bounded in both frequency and duration. Wavelet tranforms provide an alternative to more traditional Fourier transforms used for analysing waveforms, e.g. sound. analysis, as well as general data analysis techniques including chemometrics. The absolute noninvasive determination of blood glucose concentrations may also require the combination of the photoacoustic technique with other optical techniques or physical measurements.
[FIGURE 10 OMITTED]
The feasibility of the photoacoustic measurement of blood glucose has been explored in aqueous solutions and whole blood and plasma samples as well as in a gelatin phantom and noninvasively with human subjects. The in vitro study (52) has shown that the sensitivity of response to glucose is unimpaired Adj. 1. unimpaired - not damaged or diminished in any respect; "his speech remained unimpaired"
undamaged - not harmed or spoiled; sound
uninjured - not injured physically or mentally by the presence of other analytes, but it also highlights the need for high-quality spectroscopic data to eliminate the photoacoustic response produced by blood analytes other than glucose. This in vivo study has demonstrated that glucose trends can be tracked by the photoacoustic technique and may have potential for the development of a noninvasive instrument for the monitoring of blood glucose concentrations.
Current work is focusing on improving the repeatability and sensitivity of photoacoustic measurement to that required by the diabetic community as well as investigating possible detection sites on the human body and sensor design geometry for such body sites.
The overall conclusion from this initial study is that although the photoacoustic method has several promising aspects, it is possible that additional data may be required from the fund of interesting work in other areas that is being pursued in the challenging quest for the noninvasive measurement of blood glucose.
We thank the British Diabetic Association for financial assistance for initial studies. We also thank Dr. B.M. Frier for permission to study his patients.
(1.) Amos AF, McCarty DJ, Zimmett P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 1997;(Suppl 5):S1-85.
(2.) The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus insulin-dependent diabetes mellitus
Abbr. IDDM See diabetes mellitus. . N Engl J Med 1993;329:977-86.
(3.) Mastrototaro JJ, Gross TM. Clinical results from the Minimed continuous monitoring system. 31st Annual Oak Ridge Conference, April 23-24, 1999, San Jose, CA.
(4.) Khalil OS. Spectroscopic and clinical aspects of noninvasive glucose measurements. Clin Chem 1999;45:165-77.
(5.) Klonoff DC. Non-invasive blood glucose monitoring blood glucose monitoring Sugar monitoring Lab medicine The periodic testing of serum glucose in Pts known to have DM. See Bedside glucose monitoring, Beta cell implants, Diabetes, Glucometer, Glycosylated hemoglobin, Non-Invasive glucose monitoring. . Diabetes Care 1997;20:433-7.
(6.) Heise HM. Non-invasive monitoring of metabolites using near infrared spectroscopy This article is about spectroscopy. For the nonprofit nuclear energy watchdog, see Nuclear Information and Resource Service.
Near infrared spectroscopy : state of the art. Horm Metab Res 1996; 28:527-34.
(7.) Robinson MR, Eaton RP, Haaland DM, Koepp GW, Thomas EV, Stallard BR, Robinson PL. Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation. Clin Chem 1992;38: 1618-22.
(8.) March WF, Rabinovitch B, Adams RL. Non-invasive glucose monitoring of the aqueous humor of the eye. Part II. Animal studies and the scleral lens. Diabetes Care 1982;5:259-65.
(9.) Cote GL, Fox MD, Northrop RB. Non-invasive optical polarimetric glucose sensing using a true phase measurement technique. IEEE (Institute of Electrical and Electronics Engineers, New York, www.ieee.org) A membership organization that includes engineers, scientists and students in electronics and allied fields. Trans Biomed Eng 1992;39:752-6.
(10.) King TW, Cote GL, McNichols R, Goetz MJ Jr. Multispectral polarimetric glucose detection using a single pockels cell. Opt Eng 1994;33:2746-52.
(11.) Cote GL, Gorde H, Janda J, Cameron BD. Multispectral polarimetric system for glucose monitoring. SPIE SPIE International Society for Optical Engineering
SPIE Society of Photo-Optical Instrumentation Engineers
SPIE Source Path Isolation Engine
SPIE Special Purpose Insertion Extraction
SPIE Software Process Improvement Experimentation
SPIE Standard Protocols in Effect 1998;3252:36-40.
(12.) Jang S, Fox MD. Optical sensor using the magnetic optical rotatory ro·ta·to·ry
1. Of, relating to, causing, or characterized by rotation.
2. Occurring or proceeding in alternation or succession. effect of glucose. IEEE LEOS LEOS Lasers and Electro-Optics Society (IEEE)
LEOS Low Earth Orbiting Satellite Newslett 1998;12:28-30.
(13.) Berger AJ, Wang Y, Feld MS. Rapid, non-invasive concentration measurements of aqueous biological analytes by near-infrared Raman spectroscopy. Appl Opt 1996;35:209-12.
(14.) Lambert J, Storrie-Lombard i M, Borchert M. Measurement of physiologic glucose levels using Raman spectroscopy in a rabbit aqueous humor model. IEEE LEOS Newslett 1998;12:19-22.
(15.) Koo TW, Berger AJ, Itzkan I, Horowitz G, Feld MS. Measurement of glucose in human blood serum using Raman spectroscopy. IEEE LEOS Newslett 1998;12:18.
(16.) Qu J, Suria D, Wilson BC. Applications of laser Raman spectroscopy in concentration measurements of multiple analytes in human body fluids. SPIE 1998;3253:72-6.
(17.) Lakowicz JR, Szmacinski H. Fluorescence lifetime-based sensing of pH, Ca[2sup.+], [K.sup.+] and glucose. Sens Actuators 1993;11:133-43.
(18.) Bittner A, Heise HM, Koschinsky TH, Gries FA. Evaluation of microdialysis and FT-IR ATR-spectroscopy for in-vivo blood glucose monitoring. Mikrochim Acta 1997;14(Suppl):827-8.
(19.) Arnold MA, Small GW. Determination of physiological levels of glucose in an aqueous matrix with digitally filtered Fourier transform near-infrared spectra. Anal Chem 1990;62:1457-64.
(20.) Shichiri M, Uemura T, Nishida K. Non-invasive Fourier transformed infrared spectroscopy for the measurement of submucosal submucosal /sub·mu·co·sal/ (-mu-ko´sal)
1. pertaining to the submucosa.
2. beneath a mucous membrane. tissue glucose concentration--application of chalcogenide optical fiber system. IEEE LEOS Newslett 1998;12:14-6.
(21.) Marbach R, Koschinsky T, Gries FA, Heise HM. Non-invasive blood glucose assay by near-infrared diffuse reflectance spectroscopy of the human inner lip. Appl Spectrosc 1993;47:875-81.
(22.) Mendelson Y, Clermont AC, Peura RA, Lin BC. Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy. IEEE Trans Biomed Eng 1990;37:458-65.
(23.) Danzer K, Fischbacher C, Jagemann KU, Reichelt KJ. Near-infrared diffuse reflection spectroscopy for non-invasive blood-glucose monitoring. IEEE LEOS Newslett 1998;12:9-11.
(24.) Service FJ, O'Brien PC, Wise SD, Ness S, LeBlanc SM. Dermal dermal /der·mal/ (der´mal) pertaining to the dermis or to the skin.
der·mal or der·mic
Of or relating to the skin or dermis. interstitial glucose as an indicator of ambient glycemia glycemia /gly·ce·mia/ (gli-se´me-ah) the presence of glucose in the blood.
The presence of glucose in the blood. . Diabetes Care 1997;20:1426-9.
(25.) Kuriyama T. Non-Invasive blood glucose monitoring. The 8th International Conference on Solid-State Sensors and Actuators and Eurosensors IX, June 25-29, 1995, Stockholm, Sweden:108C1:447-50.
(26.) Tam AC. Application of photoacoustic sensing techniques. Rev Mod Phys 1986;58:381-431.
(27.) Patel CKN CKN Camp Kesem National (summer camps for children of cancer patients) , Tam AC. Pulsed optoacoustic spectroscopy of condensed matter. Rev Mod Phys 1981;53:517-50.
(28.) Nelson ET, Patel CKN. Response of piezoelectric transducers used in pulsed optoacoustic spectroscopy. Opt Lett 1981;6:354-6.
(29.) Freeborn SS, Hannigan J, Greig F, Suttie RA, MacKenzie HA. A pulsed photoacoustic instrument for detection of crude oil concentrations in produced water. Rev Sci Instrum 1998;69:3948-52.
(30.) Hannigan J, Greig F, Freeborn SS, MacKenzie HA. A pulsed photoacoustic system for the spectroscopy and monitoring of hydrocarbon liquids using stimulated Raman scattering in a silica fibre as a near-infrared source. Meas Sci Technol 1999;10:93-9.
(31.) Sigrist MW. Laser generation of acoustic waves in liquids and gases. J Appl Phys 1986;60:R83-121.
(32.) Sigrist MW, Bernegger S, Meyer PL. Infrared-laser photoacoustic spectroscopy. Infrared Phys 1989;29:805-14.
(33.) Sigrist MW. Trace gas monitoring by I-photoacoustic spectroscopy. Infrared Phys Technol 1995;36:415-25.
(34.) Claspy PC, Ha C, Pao YH. Optoacoustic detection of NOZ NOZ Novokuznetsk (Russia)
NOZ Neue Osnabrücker Zeitung (German)
NOZ Neue Oltner Zeitung (German) using a pulsed dye laser. Appl Opt 1977;16:2972-3.
(35.) Oraevsky AA, Esenaliev R0, Jacques SL, Tittel FK. Laser optoacoustic tomography for medical diagnostics: principles. SPIE 1996;2676:22-31.
(36.) Esenaliev R0, Oraevsky AA, Jacques SL, Tittel FK. Laser optoacoustic tomography for medical diagnostics: experiments with biological tissues. SPIE 1996;2676:84-90.
(37.) Oraevsky AA, Esenaliev R0, Karabutov A. Laser optoacoustic tomography of layered tissue: signal processing. SPIE 1997; 2979:59-70.
(38.) Poulet P, Chambron JEJ JEJ James Earl Jones (actor) . In vivo cutaneous cutaneous /cu·ta·ne·ous/ (ku-ta´ne-us) pertaining to the skin.
Of, relating to, or affecting the skin.
Pertaining to the skin. spectroscopy by photoacoustic detection. Med Biol Eng Comput 1985;23:585-8.
(39.) Tam AC, Coufal H. Photoacoustic generation and detection of 10-ns acoustic pulses in solids. Appl Phys Lett 1983;42:33-5.
(40.) Busse G, Rosencwaig A. Subsurface Imaging with photoacoustics. Appl Phys Lett 1980;36:815-6.
(41.) Kruger RA, Liu P. Photoacoustic ultrasound: theory. SPIE Laser-Tissue Interaction V 1994;2134A:114-8.
(42.) Kruger RA, Liu P. Photoacoustic ultrasound: experimental results. SPIE Laser-Tissue Interaction V 1994;2134A:119-21.
(43.) Beenen A, Spanner G, Niebner R. Photoacoustic depth-resolved analysis of tissue models. Appl Spectrosc 1997;51:51-7.
(44.) Hoelen CGA, de Mul FFM FFM Frankfurt Am Main
FFM Fat-Free Mass (muscle)
FFM Female Female Male
FFM Full Face Mask (diving)
FFM Final Fantasy Movie
FFM Fundus Flavimaculatus
FFM Frequent Flyer Mile(s) , Pongers R, Dekker A. Three-dimensional photoacoustic imaging of blood vessels in tissue. Opt Lett 1998; 23:648-50.
(45.) Watanabe T, Tamura A, Yoshimura Y, Nakazawa H. Determination of melanin in human hair by photoacoustic spectroscopy. Anal Biochem 1997;254:267-71.
(46.) Puccetti G, Lahjomri F, Leblanc RM. Pulsed photoacoustic spectroscopy applied to the diffusion of sunscreen chromophores in human skin: the weakly absorbent regime. J Photochem Photobiol B Biol 1997;39:110-20.
(47.) Christison GB, MacKenzie HA. Laser photoacoustic determination of physiological glucose concentrations in human whole blood. Med Biol Eng Comput 1993;31:284-90.
(48.) Klonoff DC, Braig J, Sterling B, Kramer C, Goldberger D, Trebino R. Mid Infrared spectroscopy for non-invasive blood glucose monitoring. IEEE LEOS Newslett 1998;April:14-5.
(49.) Boulnois JL. Photophysical processes in recent medical laser developments: a review. Lasers Med Sci 1986;1:47-66.
(50.) Ashton HS, MacKenzie HA, Rae P, Shen Shen, in the Bible, place, perhaps close to Bethel, near which Samuel set up the stone Ebenezer. YC, Spiers S, Lindberg J. Blood glucose measurements by photoacoustics. In: Scudieri F, Bertolotti M, eds. Photoacoustic and Photothermal Phenomena: Tenth International Conference. AIP AIP acute intermittent porphyria.
AIP Acute intermittent porphyria conference proceedings 463. New York: The American Institute of Physics, 1999:570-2.
(51.) Quan KM, Christison GB, MacKenzie HA, Hodgson P. Glucose determination by a pulsed photoacoustic technique using a gelatin based phantom. Phys Med Biol 1993;38:1911-22.
(52.) MacKenzie HA, Ashton HS, Shen YC, Lindberg J, Rae P, Quan KM, Spiers S. Blood glucose measurements by photoacoustics. OSA 1. OSA - Open Scripting Architecture.
2. OSA - Open System Architecture. TOPS 1998;22:156-9.
(53.) MacKenzie HA, Christison GB, Hodgson P, Blanc D. A laser photoacoustic sensor for analyte detection in aqueous systems. Sensors and Actuators B 1993;11:213-20.
(54.) Clarke WL, Cox D, Gonder-Frederick LA, Carter W, Pohl SL. Evaluating clinical accuracy of systems for self monitoring of blood glucose. Diabetes Care 1987;10:622-8.
(55.) Buijs K, Choppin GR. Near-infrared studies of the structure of water. I. Pure water. J Chem Phys 1963;39:82035-41.
(56.) Lin J, Brown CW. Spectroscopic measurement of NaCl and seawater salinity in the near-IR region of 680-1230 nm. Appl Spectrosc 1993;47:2:239-41.
(57.) Peuchant E, Salles C, Jensen R. Determination of serum cholesterol by near-infrared reflectance spectrometry. Anal Chem 1987; 59:1816-9.
(58.) Kelly JJ, Kelly KA, Barlow CH. Tissue temperature by near-infrared spectroscopy. SPIE 1995;2389:818-28.
HUGH A. MACKENZIE,  * HELEN S. ASHTON,  STEPHEN SPIERS,  YAOCHUN SHEN,  SCOTT S. FREEBORN,  JOHN HANNIGAN,  JOHN LINDBERG,  and PETER RAE 
 Department of Physics, Heriot-Watt University, Riccarton, Edinburgh EH14 4-AS, Scotland.
 Department of Clinical Biochemistry, Western General Hospital, Edinburgh EH4 2XU, Scotland.
* Author for correspondence. Fax 44 131 451 3136; e-mail H.A.MacKenzie@hw.ac.uk.
Received May 12, 1999; accepted June 28, 1999.
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|Title Annotation:||Oak Ridge Conference|
|Author:||MacKenzie, Hugh A.; Ashton, Helen S.; Spiers, Stephen; Shen, Yaochun; Freeborn, Scott S.; Hannigan,|
|Date:||Sep 1, 1999|
|Next Article:||In vitro diagnostics in diabetes: meeting the challenge.|