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Technical Insight

LEDs light up medical diagnostics (Cover Story)

Medical diagnostic systems that measure the oxygen content of the blood or allow non-invasive imaging of the eye are benefiting from optoelectronic devices such as LEDs and superluminescent diodes, says Daniel McGraw of Light Diagnostics.
Medical diagnostic systems produce quantitative measurements that help doctors to diagnose and treat a range of illnesses accurately. For example, with the help of new LED-based diagnostic instruments that measure oxygen in the blood, a doctor is able to pronounce not only that you have a heart rate of 64 beats per minute, but that 93% of the hemoglobin molecules in your arteries are carrying this gas; or to conclude that the nerve fiber layer of your retina is suffering from an early stage of degeneration. This article examines how LEDs are being used to diagnose a patient s state of respiratory and retinal health, and how these relatively simple optoelectronic devices could provide a bright future for photonic diagnostics in medicine. Pulse oximetry Pulse oximetry is currently the most successful optoelectronic-based diagnostic application in medicine. The worldwide market for these systems more than half of which are sold in the US is currently around $450 million per year and is projected to grow to $600 million by 2003 (see Pulse Oximeters A Global Strategic Business Report, Global Industry Analyst Inc, Fremont, CA, for further information). Most pulse oximeters consist of a probe that contains two LEDs one infrared and one visible which is pressed against the finger (). The probe monitors the pulse rate and the amount of oxygen saturation in the arteries (i.e. the fraction of arterial hemoglobin that is carrying oxygen), and it can be used in applications ranging from endoscopic surgery to neonatal intensive care and dentistry. Initial observations of the near-infrared light transmission in tissue led to the development of a probe based on a filtered incandescent lamp and fiber optics. However, the subsequent direct coupling of LEDs to tissue has largely enabled the application. This is because of the stable center wavelength and high intensity provided by LEDs at low cost, in addition to a modulation bandwidth capability at megahertz frequencies. For this application the ideal sources are red (660760 nm) and infrared (880 940 nm) LEDs based on highly efficient GaAs. Typically, LEDs for these applications are almost exclusively supplied by Japanese companies, including Shin-Etsu and Showa Denko. Anesthesiology One of the most important applications has been in the field of anesthesiology. Prior to 1982, determining whether a patient had sufficient oxygen under a general anesthetic was a very tricky business. One study found that 20% of patients underwent potentially dangerous hypoxic episodes, defined as an oxygen saturation of less than 81% a point below which brain damage can begin after 10 to 20 minutes. In addition, 7 out of 10 of these episodes went undetected by the anesthetist. As accurate LED-based pulse oximeters came onto the market in the 1980s, mortality among healthy patients undergoing anesthesia dropped considerably in one study it was estimated that cases decreased from 1 in 10 000 to 1 in 100 000. How it works It is well known that a person deprived of oxygen appears to turn blue. This is due to the stronger absorption of red light by non-oxygenated hemoglobin compared with oxygenated hemoglobin. What is not so well known is that we blush with every heart beat or pulse. While this effect is too small to be detected with the naked eye, it can be continuously monitored using an LED-based oximeter that probes the tissue of the finger. In essence the LED is used as an intense light source to observe the modulation or change in light transmission (or reflection) resulting from the pulsing blood, which is itself due to an expansion under pressure of the arterial volume fraction. The amplitude of this modulation is about 3% of the transmitted intensity, which is well within the sensitivity range of an LED-based instrument. The finger probe consists of two LEDs pressed against one side of the patient s finger and a silicon photodiode on the other side. The LEDs are modulated at kilohertz frequencies and the light transmitted through the finger is detected by the photodiode and a transimpedance amplifier. Typically, one of the LEDs is a red emitter that contains an active region based on AlGaAs and it has a wavelength centered on 660 nm. The other is a GaAs-based diode operating in the near-infrared at 940 nm. The instrument maintains a running average of the red to infrared transmission modulation ratio using the two different wavelengths. These measurements are then combined with a calibration table to assign a unique oxygen saturation to each measured ratio. A labor market Future sales of oximeters could be substantially increased when the technique is extended to fetal oximetry, where the probe can be used to monitor whether a fetus is receiving enough oxygen during labor and delivery. Last year an instrument company called Tyco/ Nellcor received permission from the Federal Drug Administration to sell an LED-based fetal pulse oximeter in the US. This application requires the resolution of smaller (0.11.0%) transmission modulations and the use of LEDs operating at wavelengths above 700 nm. The longer wavelength optimizes the accuracy at low oxygen saturation, which is commonly found in babies. In addition, innovative packaging is needed to allow the optoelectronic probe to be attached to the baby s scalp during labor and delivery. Interestingly, the main value of such a device may not be in lowering the already low birth mortality rate in the US, but rather to prevent unnecessary cesarean section deliveries. Cesarean section is the most common form of major surgery in the US and currently accounts for about 25% of all deliveries. This high rate is caused in part by the lack of good diagnostics for fetal distress. Improved fetal monitoring could therefore reduce the number of cesarean sections to 5%. Optical coherence tomography Another important use of optoelectronic devices is as an illumination source for optical coherence tomography (OCT), a technique that non-invasively creates depth profile images of the human retina. Previously this has been achieved post mortem by taking sections for examination using microscopy. Commercially available instruments for retinal optical cross-sectioning are now used to diagnose and treat retinal diseases such as macular degeneration and glaucoma. The superluminescent diode Commercial OCT scanning systems use a superluminescent diode (SLD) to provide the illumination used to image the retina. The SLD is a lesser-known hybrid of the LED and laser diode that can be described as a laser without an oscillator, or alternatively as an LED with a waveguide. In this case, mirror facets are not incorporated into the SLD, in order to repress stimulated emission that would lead to a narrow band source. The emitter is a promising source of high brightness and short coherence length. The latter property is due to the broader bandwidth and determines the depth resolution (a broader spectrum creates a higher depth resolution). In fact the SLD has a bandwidth-brightness product several orders of magnitude greater than laser diodes, LEDs or similar light sources. This makes it a potential source for a host of other physical metrology applications that require a low coherence source. The SLD is used in a Michelson interferometer configuration to provide depth scanning. This uses a scanning reference mirror to depth-resolve the back-scattered light, and transverse scanning is used to build a two-dimensional image. SLDs used in the commercial OCT system made by Humphrey Instruments/ Zeiss have a bandwidth that is 34% of the mean emission wavelength. A typical SLD has a ridge-type waveguide structure designed to provide a very low reflectivity from the end facets, so the emission arises almost entirely from a single pass through the device. The feedback is kept below the threshold for the onset of laser oscillation. This is important because it maintains a broad and smooth spectral output similar to that of an LED. In addition, the high brightness of the ridge waveguide structure allows efficient coupling into single-mode fiber, which allows the system to also be used in endoscopes to peer into the walls of intestines and arteries. The GaAs/AlGaAs-based device operates at around 830 nm, although longer wavelengths can also be used to increase the penetration depth. Increasing resolution Improvements to the resolution of OCT can be achieved through the use of a broader spectral emission source. and shows how an ultra-broadband source (a mode-locked titanium-sapphire laser) can be used to produce dramatically improved (1 m) images of the retina from live patients. At 260 nm, the laser bandwidth is about 30% of the center wavelength. This compares with an SLD source with a 3% bandwidth, which typically achieves around 11 m resolution when employed in the commercial instrument. However, the titanium-sapphire laser comes with a price tag of around $200 000. This bodes well for optoelectronic light sources such as the SLD: the current SLD-based OCT system costs around $30 000, and, while 70 nm bandwidth sources are becoming available, it is feasible that a higher-resolution system using an SLD with a spectral band-width up to 150 nm will be achieved. A relatively inexpensive optoelectronics-based solution to this problem will enable a new generation of non-invasive disease diagnosis in future. Potential new applications Another potential area of application is in the treatment of neonatal jaundice, which is currently treated with phototherapy. This assists the liver in breaking down bilirubin a product of hemoglobin decay generated in large quantities following birth into a form that is easily removed. The jaundice manifests itself as a yellowing, which is caused by the bilirubin absorbing blue light in the skin. Phototherapy systems for this application use blue fluorescent lights operating at 447 nm, but recently introduced high-brightness 470 nm blue LEDs could also feasibly be used to increase the rate of bilirubin breakdown. A high concentration of bilirubin is toxic to infants, so it is important to have an efficient phototherapy system. An LED-based illumination system may be more effective here for two reasons: the longer wavelength of the commercially available blue LEDs compared with existing fluorescent lamps allows more efficient photo-decomposition of bilirubin in the presence of the strong hemoglobin absorption. In addition, LEDs generate considerably less heat and would allow a closer, and therefore more efficient, illumination of the baby. A system could be envisaged where LEDs placed on a flex circuit are fashioned into a blanket, which would replace the banks of high-power fluorescent lights currently being used in neonatal intensive care. Whether for sensors, phototherapy or non-invasive imaging, recent advances in LEDs seem destined to shed a new light on medicine.
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